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Liver Buds to the Rescue

Some 16,000 ailing Americans are waiting to receive a liver transplant. But due to a shortage of viable livers, it's likely that fewer than 7,000 transplants will be performed in 2013. In Japan, where the shortage is worse, the number of people in need of new livers is 10 times as great as the number of deceased donors who could provide one.

That gap motivated stem cell biologist Takanori Takebe and his colleagues at the Department of Regenerative Medicine at Yokohama City University in Japan to find an alternate solution. This year they succeeded in generating mini-livers, or liver buds, from stem cells that were taken from human skin and reprogrammed to an embryonic state. (Embryonic stem cells are notable because they can morph into virtually any cell type in the body.)

When mixed with two other types of cells, the fabricated primitive liver cells organized themselves into three-dimensional structures, complete with blood vessels. In effect, Takebe's team re-created the process by which a human embryo begins to form a functioning liver.

Transplanted into a mouse, the human liver buds, about 5 millimeters long, exhibited many functions of the mature organ, such as metabolizing sugars and drugs. When the scientists disabled the mouse's own liver, the human buds kept the animal alive for two months. A person with liver failure would require an infusion of "tens of thousands" of liver buds, Takebe says.

Until the buds can be generated from the skin of each individual patient, recipients will have to rely on immune-suppressing drugs to avoid rejection, just as they would with the transplant of an entire organ. Replacement liver buds might be available to human patients in a decade or less. - Jeff Wheelwright

Growing Brain Organoids

Scientists can't yet grow spare parts of the human brain to fix neurological injuries or defects, but they have recently used stem cells to create brain organoids, formations of cells that mimic some of the brain's regions. A team led by neuroscientist Jürgen Knoblich of Austria's Institute of Molecular Biotechnology developed the organoids to help them simulate disease.

Two types of stem cells were used to produce the mini-brains: embryonic cells and adult cells that had been reprogrammed to a starter state. The cells were put into a special culture and then suspended in a gel and stimulated by nutrients, all geared to turn them into neurons like those found in the cortex.

The neurons literally "self-organized," according to Knoblich, and after several weeks formed three-dimensional structures about one-tenth of an inch in diameter.

"If you zoom out and look at the whole, it's not a brain," Knoblich says. "But our cultures contain individual brain regions that have a functional relationship with one another." Besides the dorsal cortex, researchers were able to grow, among other regions, parts of the ventral forebrain, which makes neurons that connect to the cortex, and the choroid plexus, which generates spinal fluid.

In their most impressive experiment, the scientists derived organoids from the skin cells of a person affected by microcephaly. This genetic disorder causes a drastic reduction in brain size and stature. The microcephalic organoids were smaller than the organoids grown from healthy people, apparently because the patient's stem cells had divided too early and became depleted.

"What our organoids are good for is to model the development of the brain and to study anything that causes a defect in development," Knoblich says. For example, by taking neural stem cells from a patient with schizophrenia, researchers might turn back the clock and track the onset of the condition in an organoid. Knowing how schizophrenia starts might help prevent it. - Jeff Wheelwright

Human Stem Cells Made From Eggs

It was 1996 when biologists first fused a mammalian skin cell with an egg cell, cloning Dolly the sheep. That was the start of the race to make a human embryo the same way. The method, called somatic cell nuclear transfer (SCNT), replaces the DNA in an egg cell's nucleus with the genetic material from the nucleus of a skin cell, then tricks the egg cell to start dividing as if it had been fertilized with sperm.

The result: an embryo that is an almost perfect genetic copy of the skin cell donor. In humans, the goal of SCNT is "nonreproductive cloning" - making embryos, then removing stem cells from the embryo and cultivating them to grow into tissues that could cure diseases, replace organs and heal injuries.

But getting eggs to act like embryos turned out to be far more difficult in humans than in sheep. It wasn't until 2013 that Shoukhrat Mitalipov of the Oregon Health and Science University finally made SCNT work in humans, through careful tweaking and fine-tuning based on experiments with more than 1,000 rhesus monkey eggs. His final protocol requires a few dozen steps.

"It's a very complex procedure," he says. Among Mitalipov's secrets: stimulating reprogramming activity by priming the eggs with caffeine and by precisely dosing them with chemicals that coil and uncoil DNA's twisted strands, and applying a gentle electric jolt to get the egg to begin dividing. (An embryo created this way will not develop into a fetus.)

There are now other methods to make stem cells, but those made via SCNT have unique value because they are genetic copies of the living person who donated the skin cells (other methods either use foreign cells or involve genetic reprogramming). Thus, replacement tissues made from them shouldn't trigger the immune system rejection that dooms many transplants.

Making purpose-built tissues may be far in the future, because figuring out the exact recipes to turn cells into functioning bone, heart or spinal cord will take time. But Mitalipov's triumph has big near-term benefits in giving researchers a new tool to understand all the details of how stem cells grow, divide and differentiate, says Larry Goldstein, director of the University of California San Diego Stem Cell Program: "It's great science." - Kat McGowan

[This article originally appeared in print as "Stem Cell Future."]

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Scientists Make Progress in Growing Organs From Stem Cells

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Some 16,000 ailing Americans are waiting to receive a liver transplant. But due to a shortage of viable livers, it's likely that fewer than 7,000 transplants will be performed in 2013. In Japan, where the shortage is worse, the number of people in need of new livers is 10 times as great as the number of deceased donors who could provide one.

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Sausages could soon be grown in a laboratory Maryanne Demasi uncovers how Dutch scientists are creating slaughter-free meat

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Explanation of what a designer baby is

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Genetic Engineering Will Change Everything Forever – CRISPR

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Australians are in love with cosmetic procedures - we spend an estimated $1 billion on them annually. The major growth is in anti-ageing procedures that don't involve a scalpel. But we've moved way beyond Botox: the latest cosmetic procedures are all about using our own biological material to restore the skin's volume.

People who once baulked at the money and time required for a traditional facelift (which costs $20,000 on average and takes weeks to recover from) are now considering these cheaper, less invasive options. Over the past decade or so there have been major advances in this area, and there is more still to come.

Here are the latest techniques to give skin back its bounce.

Stem-cell facelifts

Stem-cell facelifts are the next step in fat transfer and are already being used both here and in the US.

"It's an exciting advance in anti-ageing procedures but it's still early days," says Dr John Flynn, CEO of the Australasian College of Cosmetic Surgery.

Fat transfers have been around for more than a decade and have been used to attempt to increase the volume in ageing skin. Previously, the fat was extracted from the patient's hip and reinjected into their cheeks.

However, the cells often died. Now, scientists can identify stem cells in fat, extract them and combine them with the patient's own fat. This concentrated filler is far more effective.

Fat transference is just the start of the treatments that may develop using stem cells. In the future, they may be used to produce fibroblasts (the principal connective tissue cells), which will help to produce more collagen and elastin.

Cost: Stem-cell facelifts start at $3500. Contact the Australasian College of Cosmetic Surgery for surgeons who will perform this technique.

Blood injections

Autologous blood injections, otherwise known as "vampire facials", were developed about five years ago to treat degeneration of tendons but are now used in cosmetic procedures.

In the procedure, blood is removed from the patient, the platelet-rich plasma is separated and then injected into areas such as the cheeks, above the lip and around the eyes. The platelets contain human growth hormone and growth factors to help boost collagen production.

The latest development is to combine blood injections with a treatment such as resurfacing with a Pearl laser, which cosmetic physician Dr Joseph Hkeik says is more effective.

The Pearl laser makes microscopic holes on the surface of the skin, which traumatises the fibroblasts and causes them to produce extra collagen.

Recovery usually takes four to five days, but when the procedure is combined with an autologous blood injection, the recovery time is shortened by a day and the results are better, Dr Hkeik says.

Cost: Pearl laser costs $2000 for a full face. Pearl fusion, which is more intense and suitable for acne scarring and anti-ageing, costs $3500. Adding an autologous blood injection costs an extra $500.

Botox and fillers

Injectables are by far the most popular cosmetic treatments in Australia. Botox is still the most popular, and has been around since the late 1980s, but Dysport is a more recent addition. Both are designed to relax muscles and make expression lines less obvious. Dysport is cheaper per unit than Botox, but Dr Hkeik says you need up to three times as much for the same result.

The world of fillers was revolutionised in the 1990s when cosmetic surgeons first started used hyaluronic acid instead of collagen in their injections, in brands such as Restylane and later Juvéderm.

Hyaluronic acid is found in the skin and is involved in tissue repair and maintaining moisture. It was originally extracted from rooster combs, but is now synthetically produced.

The latest development in hyaluronic acid fillers is Modélis, a thicker, firmer formulation.

"It's ideal for soft cheeks and facial sculpting," Dr Hkeik says.

Sculptra, a dermal thickener which arrived in Australia 10 years ago, is still a popular facial-sculpting technique.

It is a filler of poly-L-lactic acid that causes the skin to produce more collagen.

Cost: Botox and Dysport cost about $280 for each section of the face. The effects last for three to four months. Modélis costs $1400 for cheek and chin sculpting and lasts for 18 months to two years. Sculptra requires two to three sessions and costs between $750 to $1500 a session. The effects last for three years.

The injection-free facelift

With Pelleve, the latest celebrity fad, a current is passed through the skin, which Dr Hkeik says causes a contraction of collagen and encourages new collagen growth.

Cost: A full-face treatment requires one to three sessions and a top-up each year. Sessions cost about $820.

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Australians are in love with cosmetic procedures - we spend an estimated $1 billion on them annually. The major growth is in anti-ageing procedures that don't involve a scalpel. But we've moved way beyond Botox: the latest cosmetic procedures are all about using our own biological material to restore the skin's volume.

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Embryonic stem cell research: an ethical dilemma

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Embryonic stem cells offer hope for new therapies, but their use in research has been hotly debated. Presenting the issues, rationale and key ethical arguments.

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French researchers say they have found a way of using human embryonic stem cells to create new skin which could help serious burns victims.
They say the stem cells grew into fully formed human skin 12 weeks after being grafted on to mice.

The researchers, writing in the Lancet journal, say the skin could solve the problems of rejection that burns patients currently face.

One stem cell expert said they had made an important advance.
Burns techniques
For more than 20 years, patients with serious burns have benefited from a technique which grows new skin in the laboratory using their own skin cells.

But the technique takes three weeks, putting the patients at risk of dehydration and infection.

Skin from cadavers is used during this period to cover the wounds but its availability is limited and it is often rejected by the patient's immune system.

Artificial nets which cells can grow on have also been tried. But they do not work on large burns, where they increase the risk of rejection and disease transmission because they can contain material from cows and other humans.
Skin formation
The researchers duplicated the biological steps that lead to skin formation during embryonic development.

They placed the cells on an artificial net which helped the cells to form a layer of skin.

This was grafted on to five mice and 12 weeks later, the skin had a structure consistent with human skin.

Dr Christine Baldeschi, from the Institute for Stem Cell Therapy and Exploration of Monogenic Diseases in Evry, France, who led the research, said the results were promising.

She said the technique could lead to "an unlimited resource for temporary skin replacement in patients with large burns awaiting grafts of their own skin".

Researchers are now planning a human trial of the new technique.

An accompanying editorial by Holger Schluter of the Peter MacCallum Cancer Centre in Melbourne, Australia, said the research represented an important advance.

He said: "This report takes research into regenerative skin stem cells to the next level.

"This finding suggests that skin derived from embryonic stem cells could be transplanted onto burnt patients awaiting skin grafts, with a reduced risk of rejection."

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Stem cells could create new skin to help burns victims

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French researchers say they have found a way of using human embryonic stem cells to create new skin which could help serious burns victims. They say the stem cells grew into fully formed human skin 12 weeks after being grafted on to mice.

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Ethics and reprogramming: ethical questions after the discovery of iPS cells | Eurostemcell

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Can we decide today whether iPS cells could or should replace embryonic stem cells? And would using only iPS cells resolve all ethical dilemmas about this research? To answer these questions, we need to consider both current scientific understanding and moral aspects of the issues: Are there any ethically relevant differences between iPS cells and embryonic stem cells?

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The Ethical, Legal, and Social Issues Impacted by Modern Assisted Reproductive Technologies

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Background. While assisted reproductive technology (ART), including in vitro fertilization has given hope to millions of couples suffering from infertility, it has also introduced countless ethical, legal, and social challenges. The objective of this paper is to identify the aspects of ART that are most relevant to present-day society and discuss the multiple ethical, legal, and social challenges inherent to this technology.

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Mouse models of spinal cord injury and stem cell transplantation

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Spinal cord injury is one of the most devastating neurologic conditions that mostly affects young, and otherwise healthy, patients. Following the prim...

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Mouse models of spinal cord injury and stem cell transplantation

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Spinal cord injury is one of the most devastating neurologic conditions that mostly affects young, and otherwise healthy, patients. Following the prim...

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Updated October 09, 2011 01:49:35

Australian vets say they are having great success treating arthritic dogs with stem cells and researchers developing arthritis treatments for humans are taking a keen interest in the technique.

The trouble is that some dog owners feel their four-legged friends are getting better treatment than they are.

Melbourne vet Ray Ferguson has had a particular interest in treating arthritic dogs for about 30 years.

At first he was sceptical of the benefits of canine stem cell treatment, but he has now treated about 40 dogs.

"For individual joints where a dog has one bad knee or one bad elbow, the treatments are very simple," he said.

"A very, very light anaesthetic and we pop an injection of the stem cells straight into the joint and it's all over in about five minutes."

Dr Ferguson says the stem cells come from donor dogs.

"These largely come from dogs that are being de-sexed, they're all young dogs so we've got young, vibrant cells," he said.

Dr Ferguson says preliminary trials involved dogs with skin disease and joint disease being injected with stem cells as well, but the arthritic dogs responded best of all.

"Particularly in the early trials I did five dogs, one of which was my own that had I would say incurable lameness, persistent lameness," he said.

"They all responded and those five dogs are all sound today. That's amazing."

The stem cell treatment costs between $1,500 and $3,000.

Dr Ferguson says he tells dog owners the stem cell treatment works best on younger dogs but dogs up to about 10 years of age are also responding well.

"I have to point out to them, look I'm not offering a fountain of youth. This isn't going to turn an old dog into young dog," he said.

"But it's just a wonderful, adjunctive therapy to have to everything else that we've got."

Humans 'getting jealous'

Professor Richard Boyd is the director of Monash Immunology and Stem Cell Laboratories at Monash University.

He says the stem cell treatment of dogs is helping researchers understand the effect similar treatment would have on humans.

"Their lives are constrained into 10 or 15 years and that reflects a human going from up to 70 or 80 years," he said.

"So the conditions which are generative which a dog gets in 10 years like arthritic hips and joints is very similar to what ageing humans get.

"So we can treat these dogs and improve their health using these stem cells. But it has a double-edged advantage of being able to say to our clinicians, look we've done now 8,000 animals.

"This is a basic very good basis to being able to treat humans."

Professor Boyd says the dogs may actually be getting the better and more innovative treatment than a lot of Australians.

"The retired senior who's taking the rejuvenated dog for a walk is now getting jealous," he said.

"But I think that what we will see certainly soon is that this is sort of like the winter of stem cell research, it's now becoming the spring of stem cell therapy.

"So hopefully we'll get a retired senior and a retired dog both walking briskly along the beach."

Topics: arthritis, diseases-and-disorders, health, veterinary-medicine, animal-science, stem-cells, science-and-technology, australia

First posted October 08, 2011 14:46:40

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Updated October 09, 2011 01:49:35 Australian vets say they are having great success treating arthritic dogs with stem cells and researchers developing arthritis treatments for humans are taking a keen interest in the technique. The trouble is that some dog owners feel their four-legged friends are getting better treatment than they are.

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Modern day ark The first stem cells from endangered species have been created by a team of US scientists, a breakthrough that could potentially save dozens of animals teetering on the brink of extinction.

"The best way to manage extinction is to preserve species and habitats but that is not always working," says Oliver Ryder, director of genetics at the San Diego Zoo and co-leader of the study, said in a statement.

"Stem cell technology provides some level of hope that they won't have to become extinct even though they have been completely eliminated from their habitat."

That is the case for the northern white rhinoceros, one of the first two animals included in Ryder's new 'stem cell zoo'.

Only seven specimens remain in existence, all in captivity and two in San Diego.

The researchers also isolated stem cells from a critically threatened primate called a drill, genetically a close cousin to humans.

In captivity, drills often suffer from diabetes, a disease scientists are seeking to treat in humans using stem cell-based therapies.

Ryder's team had already collected skin cells and other tissue samples from more than 800 species, stored in a 'Frozen Zoo', by 2006.

That is when he contacted Dr Jeanne Loring, a professor at the Scripps Research Institute in nearby La Jolla and the study's other lead researcher, about the possibility of using the bank to generate and store stem cells.

Lessons from human research

At the time, scientists seeking to use stem cells to cure human disease had not yet found a reliable technique for turning normal adult cells into stem cells that can give rise to nearly any type of tissue or cell in the body.

Today, however, this process, called induced pluripotency, is routinely achieved by inserting certain genes into normal cells.

At first, Ryder and Loring tried to use genes from animals closely related to the target species in order to trigger the transformation, but the experiments failed.

Through trial and error, however, they discovered to their amazement that the same genes that induce pluripotency in humans also worked for the drill and the rhino.

The process is inefficient, only producing a few stemcells at a time, according to the study, published in the journal Nature Methods. But it was still enough to start the 'stem cell zoo'.

Creating sperm and eggs

Perhaps the greatest potential for helping endangered species, beyond disease treatment, is new reproductive strategies.

If adult stem cells can become a sperm or egg cell, for example, scientists could then use skin cells from long-dead animals in the Frozen Zoo to produce the male and female starter kit for new life.

Induced sperm cells could be combined with the eggs from living animals through in vitro fertilisation.

Alternatively, both eggs and sperm might be generated from stem cells, with the resulting embryos implanted in live host animals, a process the researchers said would likely be much more reliable that cloning techniques.

"I think that work would be a lot easier ethically with endangered species than with humans," says Loring.

"I suspect some people working in this area would love to have our cells for experiments."

Such techniques would also help boost genetic diversity by reaching beyond the small number of living individuals of a dwindling species, she explained.

Even if the remaining northern white rhinos reproduced, which hasn't happened in many years, the tiny gene pool could easily lead to unhealthy animals.

Tags: endangered-and-protected-species, animals, stem-cells, genetics

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Modern day ark The first stem cells from endangered species have been created by a team of US scientists, a breakthrough that could potentially save dozens of animals teetering on the brink of extinction.

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Breeding two highly endangered animals or subspecies through conventional mating is a difficult and often futile undertaking. For instance, the last birth of an endangered northern white rhinoceros was in 2000. As a radical alternative, biologist Jeanne Loring at the Scripps Research Institute is attempting to transform frozen skin cells from threatened species into eggs and sperm. In theory, new embryos then could be created by combining converted egg or sperm cells with natural ones, or by combining eggs with sperm cells derived from different donor animals.

Last year Loring transformed skin cells from the drill, a silver-bearded African monkey, into a pluripotent stem cell that can form many different tissue types. She did the same with cells from the northern white rhinoceros, a subspecies believed to be extinct in the wild. "It took a couple years to get conditions right," Loring says. "We had to change the delivery virus for the rhino."

The next step, transforming the stem cells into egg and sperm cells, could take years more, but Loring is convinced the results will be worth it. "People will be able to make fertile embryos and implant them into surrogate mothers," she says. This will in turn introduce much-needed diversity into the gene pool as scientists attempt to rebuild decimated populations.

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#43: Skin Cells Could Help Revive Rare Species

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Breeding two highly endangered animals or subspecies through conventional mating is a difficult and often futile undertaking. For instance, the last birth of an endangered northern white rhinoceros was in 2000. As a radical alternative, biologist Jeanne Loring at the Scripps Research Institute is attempting to transform frozen skin cells from threatened species into eggs and sperm.

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Video

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Celebrated by the 2012 Nobel Prize in Medicine, a type of cell known as an "induced pluripotent stem cell" or "iPS cell" has important implications for the emerging field of biomedical technology. In this video, Canadian scientist Dr. Mick Bhatia explains how iPS cells are created and how they can be used to create new therapies for human disease.

FURTHER INFORMATION:
What are stem cells? - stemcellnetwork.ca/index.php?page=what-are-stem-cells
Induced pluripotent stem cells - en.wikipedia.org/wiki/Induced_pluripotent_stem_cell
Dr. Mick Bhatia - sccri.mcmaster.ca/bhatia_mick.html

SCRIPT:
Most of the cells in our bodies are not stem cells.

For example, blood and skin cells are specialized. They perform specific functions in the body and they got this way through a process known as differentiation that is normally not reversible.

However, if some adult cell types are taken, grown in plastic dishes and given specific genetic instructions, over time, some of these cells will reverse from their differentiated state and develop the ability to re-differentiate into any cell type in the adult. This newfound ability is known as pluripotency, and it is why these cells are known as induced pluripotent stem cells, or iPS cells.

The creation of iPS cells from individual patients may one day allow us to develop replacement tissues that are a perfect match to the patient. In addition, the creation of iPS cells from patients with specific diseases will allow scientists to develop new drugs to treat a wide variety of disorders.

CREDITS
Narration by: Dr. Mick Bhatia
Written & Directed by: Ben Paylor & Mike Long
Produced by: Infoshots - infoshots.ca
Animation by: David Murawsky - davidmurawsky.com/
Sound by: James Wallace - imdb.com/name/nm0908691/

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What are induced pluripotent stem cells? Narrated by Dr. Mick Bhatia

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Celebrated by the 2012 Nobel Prize in Medicine, a type of cell known as an "induced pluripotent stem cell" or "iPS cell" has important implications for the emerging field of biomedical technology. In this video, Canadian scientist Dr. Mick Bhatia explains how iPS cells are created and how they can be used to create new therapies for human disease.

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Video

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Hematopoietic stem cells (HSCs) are the type of stem cell that give rise to all the other blood cells. They are located in the bone marrow, which is contained in the core of most bones and is the site where new blood cells come from. HSCs are able to give rise to both myeloid (monocytes and macrophages, neutrophils, basophils, eosinophils, erythrocytes, megakaryocytes/platelets, dendritic cells), and lymphoid cells (T-cells, B-cells, NK-cells). The study of HSCs over the past 50 years have provided us with a much clearer understanding of how the blood system works. More recent advances have resulted in the use of HSC transplants in the treatment of cancers and other immune system disorders

FURTHER INFORMATION
Hematopoietic stem cells - en.wikipedia.org/wiki/Hematopoietic_stem_cell
Dr. Connie Eaves - terryfoxlab.ca/people-detail/connie-j-eaves/
National Institute of Health "Stem Cell Reports" - stemcells.nih.gov/info/scireport/pages/chapter5.aspx

SCRIPT
Blood contains many different types of cells, such as red blood cells and white blood cells, each having specific functions. Because most of these cells live for only a few days or weeks, they need to be constantly replaced.

New blood cells are produced by hematopoietic stem cells. These rare cells are found in the hollow part of bones - called the marrow. Hematopoietic stem cells are unique because they continue to make more of themselves while also producing cells destined to become specialized blood cells.

Hematopoietic stem cells can regenerate the blood-forming system if it is damaged or destroyed. Thus hematopoietic stem cell transplants can restore blood production in patients with various blood diseases or in patients who have undergone intensive cancer therapy that destroys healthy blood cells along with cancer cells.

Such transplants are the most widespread form of stem cell therapy used today and are estimated to have saved thousands of lives in the past 50 years.

CREDITS
Narration by: Dr. Connie Eaves
Written & Directed by: Ben Paylor & Mike Long
Produced by: Infoshots - infoshots.ca
Animation by: David Murawsky - davidmurawsky.com/
Sound by: James Wallace - imdb.com/name/nm0908691/
Funding by: Stem Cell Network and Canadian Stem Cell Foundation

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What is a hematopoietic stem cell? Narrated by Dr. Connie Eaves

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Hematopoietic stem cells (HSCs) are the type of stem cell that give rise to all the other blood cells. They are located in the bone marrow, which is contained in the core of most bones and is the site where new blood cells come from.

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Our bodies contain around 37 trillion cells, of which there are hundreds of different types-liver cells, skin cells, hair cells, muscle cells, brain cells, to name just a few. These cells are specialised-they have a specific function within the body. A brain cell cannot do the job of a skin cell.

Liver cells

Hair cells

Brain cells

Skin cells

There is another type of cell-stem cells-which are an 'immature' type of cell, that have not yet developed a specialised function.

Stem cells

There are two very important things about stem cells:

they have the ability to divide and replicate themselves, to make more stem cells (self-renewal)

they can become adult specialised cells through a process called differentiation-they might go on to become a liver cell, a heart cell or a muscle cell

Most of our body's organs contain stem cells.

Tissue-specific stem cells

Some stem cells have limited options. They can usually only develop, or differentiate, into cells to replenish the organs in which they are found, replacing cells that are lost or die because of injury or disease. They also aid homeostasis GLOSSARY homeostasis The process of healthy growth and development, and maintenance of healthy functioning of an organism. in healthy tissue. These stem cells are known as tissue-specific, adult, or somatic stem cells.

Some organs, like our skin, have highly active stem cells-we're constantly rubbing away at our skin and shedding skin cells, so it's important to replace the cells we lose. We are also constantly shedding cells from our gut, so we need stem cells there to produce new cells to maintain normal function.

Stem cells are also present in other organs, like our hearts or brains, but their regenerative capacity is more limited. Understanding why the stem cells in these organs do not respond in the same way in response to injury or disease is the focus of current research.

Pluripotent stem cells

For some stem cells, the world is their oyster. Pluripotent stem cells can turn into any one of the many specialised cells-they are not restricted to any one particular type of organ or tissue.

There are two types of pluripotent stem cells:

embryonic stem cells (ES cells)

induced pluripotent stem cells (iPS cells)

The capacity to become anything-embryonic stem cells

After an egg is fertilised, it starts to divide to make new cells. As development progresses, the cells initially differentiate into two different types of cells-the inner cell mass and an outer cell layer called the trophectoderm which surrounds the embryo. This stage of development occurs 5-7 days after fertilisation. The trophectoderm cells will contribute to the placenta, and those of the inner cell mass will develop into a foetus if a pregnancy is achieved.

In stem cell research, embryonic stem cells are sourced from the inner cell mass of embryos donated by couples who have undergone infertility treatment. These early stage (pre-implantation) embryos are no longer required by the couple to achieve pregnancy (usually because they have completed their family) and if not donated to research, would most likely have been discarded. In Australia, research using embryonic stem cells, sourced from donations of excess embryos used in IVF procedures, has been legal since 2002. It is strictly regulated and scientists must justify their requirement to use embryonic stem cells to an independent licensing committee.

The art of gentle persuasion-iPS stem cells

Another way to make pluripotent stem cells is by 'forcing' or 'coaxing' specialised adult cells (like skin cells or blood cells) to revert back to an immature stem cell state. Scientists have found that reintroducing some crucial genes or adding certain proteins to the culture media containing the adult cells can turn back the 'differentiation clock', producing pluripotent stem cells capable of self-replication as well as differentiation. These are called induced pluripotent stem cells (iPS cells).

Only discovered in 2006, scientists' understanding of this process is constantly evolving, and iPS cell technology is still being refined. However, the technique has huge potential to advance stem cell research and scientists around the world are working on developing iPS cells.

iPS cells have been lauded by some as a solution to the ethical issues surrounding the use of embryonic stem cells. But in reality, it's not quite that simple. iPS cells come with a range of ethical issues of their own. As they are derived from adult cells, iPS cells will contain all of the donor's genetic material, making anonymity and privacy a potential problem. Furthermore, it would theoretically be possible to make egg and sperm cells from iPS cells, and then use these to create a new human life. This is pretty firmly in the realm of science fiction at the moment, although researchers have managed to clone mice and pigs from iPS cells. The research community stands united in staunch opposition to developing this sort of technology for human reproduction.

Understanding the process by which an embryonic stem cell or an induced pluripotent stem cell develops into a specialised cell is crucial before scientists can even begin to think about building new organs. Australian researchers led by Martin Pera are looking at how stem cells first start out on the path of differentiation, and also how neural (brain) cells develop. Find out more about the research at Stem Cells Australia.

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What we can already do with stem cells

While stem cells certainly offer great hope for future treatments, the current range of proven stem cell treatment in Australia, and indeed, around the world is quite small.

Blood treatments

Blood stem cell (haematopoietic stem cell, HSC) transplants are already routinely used to treat a number of blood and autoimmune diseases, and some cancers, like leukaemia, lymphoma and thalassaemia. The HSCs help the patient's bone marrow (which makes red blood cells, white blood cells of the immune system and platelets) function properly again. HSCs can be sourced from bone marrow or from umbilical cord blood. In the former, HSC production is stimulated by introducing a growth factor called GCSF into the patient's blood circulation that encourages their growth. This can be time consuming and can have side effects such as bone pain and spleen enlargement for some patients. CSIRO has recently carried out pre-clinical trials on a new method of harvesting stem cells which eliminates the need for the growth factor.

Corneal grafts

Treatments involving stem cells from the cornea have successfully helped people suffering from eye disease or injuries to the surface of the eye. Stem cells from the edge of the cornea, known as the limbus, are taken from the patient and used to grow new corneal tissue in the laboratory. The new tissue is then grafted on to the patient's eye.

Skin grafts

Using skin stem cells to treat burns has been a common and effective treatment for decades. Using skin stem cells from the patient, new skin is grown in the laboratory and then grafted over the injured area. The process of growing the new skin takes around three weeks, during which the patient may suffer from dehydration or infections. Although the practice of using stem cells to create skin grafts has been around a long time now, it is still being refined. Each new development means limitations can be overcome, and more patients can be successfully treated.

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Treatments in the future

Scientists in the lab are continually redefining the line between scientific reality and science fiction. Almost daily, new results are announced that reinforce the potential of stem cells to revolutionise doctors' capacity to help patients with serious injuries or diseases.

Several researchers around the world have been able to grow types of tissues dubbed 'organoids' from stem cells. These tissues resemble the structure and function of actual human organs. Tiny human intestines have been grown in mice, after researchers from the Cincinnati Children's Hospital Medical Centre implanted intestinal cells made from iPS cells. A completely functional thymus was grown in a mouse by researchers at the University of Edinburgh, marking the first time a full organ has been grown using stem cells.

Hans Clevers and his collaborators are developing methods to study cancer and other diseases in organoids of gut and intestinal tissues, growing 'mini-guts' from stem cells.

A team led by cardiologist James Chong including researchers from the University of Sydney, Sydney's Westmead Millennium Institute and the University of Washington has managed to regrow damaged heart tissue using human embryonic stem cells. The stem cells were injected into monkeys that had suffered heart attacks, and 40 per cent of the damaged tissue went on to repair itself. The new heart cells then began to beat in rhythm with the rest of the heart.

A group of researchers led by Melissa Little at the Murdoch Childrens Research Institute have produced a tiny kidney similar to that seen during foetal development. The kidney is a large and complex organ with many different types of cells, so it remains a challenge to grow an entire mature kidney the lab, but down the track, it may be possible to grow kidneys large enough to offer some sort of limited filtering function to patients. However, the ability to grow even these early stage kidney cells provides a valuable tool to study kidney development, carry out more directed research on specific mutations in kidney growth and to test new drugs.

All of this work feeds one of stem cell researchers' biggest aspirations: being able to regrow or repair damaged human tissue, or even better, create entire brand new organs.

Not just growing new organs

Sometimes it's not an entire organ that needs replacing. People suffering from some autoimmune diseases, where the patient's immune system attacks its own body, may also benefit from developments in stem cell research, particularly where there is only a single type of cell affected by a disease.

Type 1 Diabetes

Type 1 diabetes occurs when a person's immune system attacks the pancreas, destroying the cells that produce insulin. Without enough insulin, our body's cells can't absorb sugar properly and it builds up in the bloodstream, eventually damaging the kidneys, blood vessels and the retina.

A team led by Doug Melton have used embryonic stem cells to create insulin-producing cells that when transplanted into mice, responded to glucose by producing insulin. More research is needed to ensure this treatment is safe and effective in the long term and a viable option for people.

A further consideration is that transplantation of these cells in humans would have to be accompanied by treatments that curb the destructive action of the person's immune system, so that the new cells aren't damaged as well. An American company called ViaCyte is developing a system where stem cell precursors of insulin-producing beta cells are implanted into a patient within a protective 'scaffold'. They then grow into mature beta cells capable of secreting insulin. The scaffolding protects the cells from the immune system's antibodies that would destroy them and also prevents the cells diffusing into the body.

Scientists at Monash University and the University of Sydney have also used skin cells from patients with type 1 diabetes to develop iPS cells which they can use to study how the disease works and to test new drugs.

Multiple sclerosis

Multiple sclerosis (MS) is a disease where the body's immune system attacks its own myelin, which is a protective covering for the central nervous system.

This impacts upon the body's nervous system to effectively transmit messages to the brain. A potential treatment involving haematopoietic stem cells for aggressive forms of the disease is currently in clinical trial stage in both the USA and Australia. It involves taking haematopoietic stem cells from the patient, then destroying their immune system with high-dose chemotherapy. The stem cells are then transplanted into the patient, with the hope that they will 'rebuild' a healthy immune system, without the damaging effects of the disease. Results from trials of this treatment and the small number of patients that have received the treatment have been mixed. While some patients do appear to benefit in the short term from the treatment, there is still no conclusive evidence that it will prove to be an effective long-term treatment.

Other research groups are trying to understand more about the role of stem cells in the brain and whether they can be reactivated to help combat the damage to nerves that occurs in multiple sclerosis.

Parkinson's disease

Parkinson's disease is a condition in which the dopamine-producing cells in a person's brain degenerate and die, leaving the person unable to properly control their body's movements. As there is only a small subset of nerves involved in this disease, it seems that stem cell therapy that aims to replenish those nerves could be a possible treatment. Scientists have been able to train both embryonic and iPS stem cells to become the specific type of brain cell that is affected by Parkinson's disease. They have also been able to transplant these cells into the brains of mice, rats and monkeys, which improved some symptoms.

However, one of the issues with trying to treat Parkinson's disease with stem cells is that several experiments have shown that after the stem cells are transplanted into a test animal's brain, while some of them differentiate into the desired dopamine-producing neurons, many stem cells simply keep self-replicating, and form tumours. Clare Parish and Lachlan Thompson from the Florey Neuroscience Institutes and the University of Melbourne have developed a method where they can isolate the extra stem cells from the useful dopamine-producing cells in the lab, and discard the extra stem cells before they perform the transplant.

Work is continuing to ensure that this treatment doesn't result in the growth of tumours, is effective in the long term and also to find ways to make the transplanted cells produce sufficient amounts of dopamine to restore function for Parkinson's patients. It is only through carefully conducted clinical trials that these challenges will be resolved.

Macular degeneration

A recent study found that stem cell therapy could be effective in improving the eyesight of people suffering from macular degeneration. Embryonic stem cells were turned into retinal pigment cells and injected behind the retinas of one of the study patients' eyes. After monitoring their progress over three years, their eyesight had improved by several lines on a vision chart, and some of them were able to read a computer for the first time. Researchers were concerned about whether the stem cells might start proliferating without stopping, which could turn into tumours, but happily this did not eventuate in this study. The improvements found in the research are a good sign for future possible treatments for degenerative eyesight diseases but further refinement and testing, as well as long-term monitoring is required.

Still work to be done

Other stem cell treatments that make the headlines, such as treatments for spinal cord injury, offer some people hope when all other avenues seem to lead to dead ends. However, these treatments are not approved and have not yet gone through the rigorous clinical trial process to ensure that they are safe, let alone effective. Although there have been reports of miracle cures using stem cells, other outcomes of these experimental and unproven treatments have been less successful, and even tragic. We just don't know enough yet about the long term consequences of stem cell treatments. Stem cell treatments offer huge promise, but it must be balanced with sensible caution.

Complications sometimes only show up down the track, as was the case with a woman who had stem cells from her nose implanted into her spine to try and treat paralysis. Not only did the treatment not work, but eight years later she needed surgery to remove a three centimetre g rowth of nasal tissue that had formed on her spine.

Disease in a dish

While growing new organs and fixing damaged spinal cords is definitely exciting and headline-making science, there is another less celebrated, but probably even more promising avenue for stem cell research: the ability to grow disease-affected cells. A sample of skin cells from a patient with particular diseases can be taken and reprogrammed to become stem cells. These iPS cells can then be turned into the diseased cells. Scientists can study the diseased cells to better understand both the disease's progression and develop possible ways to treat it. It also provides an ideal guinea pig to test new drugs before trying them out on actual patients.

This is particularly useful for conditions that affect areas of the body that are difficult to take samples from, such as motor neurone disease, which affects the brain and spinal cord. This method also provides opportunities to study rare diseases that don't always receive as much attention or funding as other more prominent conditions.

Researchers at the University of Queensland are investigating both Down syndrome and Alzheimer's disease using iPS cells that were derived from patients; skin cells. Down syndrome causes brain changes that are similar to those that occur with Alzheimer's disease. By developing the Down syndrome affected iPS cells into brain cells, the researchers can study the genetic characteristics of the diseases and attempt to identify pathways for treatments.

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Ethical considerations

More than just where they come from

For some in the community, the announcement in the late 1990s that scientists were able to create stem cells from human embryos raised significant concern. They viewed the use of human embryos as destruction of human life, shrouding stem cell research in controversy. For others, the potential of medical research to help those suffering from incurable disease outweighed these concerns-particularly when stringent legislation was introduced in Australia that limited the use of human embryos to circumstances where the early stage embryos had been originally created for infertility treatment but were no longer required and would otherwise have been discarded.

Over the past decade, with strong public support for the use of stem cells in both research and treatment of disease, the debate has largely moved on. Controversy now lies in the land of the hope-peddling stem cell treatments that promise much but are less specific on what they can actually deliver. The hope that stem cell treatments can offer has spawned an industry where providers offer unproven and potentially unsafe experimental treatments ... for those who are willing to pay.

In Australia, these sorts of treatments are generally offered by doctors operating outside of the clinical trial space. Overseas, the picture gets even more confused.

Stem cell tourism, where desperate patients and their carers travel overseas to countries to receive unproven treatments that are not offered in Australia for precisely that reason-they are unproven, and as such, could very well do more harm than good. With 'do no harm' being the central tenet of medical practice, doctors do not want to risk the health that patients do have on a risky and potentially threatening treatment.

Often the providers of these treatments make exaggerated claims about what they can achieve, without necessarily having any solid evidence, relying strongly on patient testimonials. But anecdotes are no substitute for impartial evidence obtained through rigorous research and a thorough clinical trial process. Playing on the perception that Australia is behind the times with respect to new stem cell treatments, or that medical doctors and researchers are in the pocket of Big Pharma who have agendas to restrict the treatments available to patients, these operators market a compelling solution-but at what cost? The reality is that we are at the very early stage of developing new treatments and progress needs to continue based on evidence rather than hype.

It's clear that stem cells offer great hope for the future. That hope needs to be harnessed, and channelled into valuable research that will have the potential to benefit people suffering from a huge range of diseases and conditions with safe and effective treatments.

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Stem cells-sorting the hype from the reality

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Our bodies contain around 37 trillion cells, of which there are hundreds of different types-liver cells, skin cells, hair cells, muscle cells, brain cells, to name just a few. These cells are specialised-they have a specific function within the body. A brain cell cannot do the job of a skin cell.

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While human tissue has always had cultural, educational and scientific value, it is only in the past 40 years that tissue economies have begun to emerge. 1 These economies have been driven by advances in technology that rapidly reversed our perception of human tissue as a useless by-product of treatment, to being a valuable and powerful source of wealth. Umbilical cord blood banking is an excellent example of this trend - what once was waste is now considered to be a wonder product that is collected, stored and traded in private and public markets. 2 As a consequence, cord blood stem cells have become a focus of public, medical and scientific contest because of their uncertain ontological status (whether they are simply adult stem cells or share properties of both embryonic and adult stem cells), and because they have proven value as a source of haematopoietic stem cells for transplantation and more speculative value as a source of autologous stem cells for regenerative medicine.

Therapy and research: proof and potential

The benefits of cord blood stem cells in haematopoietic stem cell transplantation (HSCT) are clear. They are easily (non-invasively) collected and stored, they provide a rapidly available source of stem cells for HSCT, they extend the number of patients for whom HSCT is an option (because of their immunological immaturity), and they have been shown to give clinical outcomes equivalent to HSCT using bone marrow or peripheral blood stem cells. 3 The benefits of cord blood transplantation rely primarily on the altruistic donation of cord blood around the world to an international network of more than 54 public cord blood banks, which collect, process, store and supply cord blood units (CBUs) for transplantation in Australia and internationally.

In contrast, the banking of autologous cord blood in private cord blood banks is based on the hope that it may, at some point in the future, be of therapeutic benefit in treating or curing any form of chronic or degenerative disease in its donor or in others. At present, this is entirely speculative. The likelihood that the infant, or other family members, will need access to their cord blood haematopoietic stem cells for established therapeutic indications is extremely low. For the most part, such use would be largely unnecessary, as most patients who need an autologous HSCT have haematopoietic stem cells collected from their peripheral blood or bone marrow when required. 4 Despite the absence of indications for this use of cord blood, many parents elect to bank their child's cord blood as a form of biological insurance, in the belief that such benefits may be recognised in the future - or at least to satisfy themselves that they have done everything in their power to guarantee their child's wellbeing. There are now 225 private cord blood banks worldwide, storing nearly 1 million CBUs, which far exceeds the estimated 600 000 CBUs that are stored in publicly accessible cord blood banks. 5

The emergence and rapid growth of private cord blood banks provides a significant challenge to the viability of public cord blood banks - a challenge that is likely to grow if evidence accumulates regarding cord blood stem cells' utility in regenerative medicine. 6 This challenge is both philosophical and practical. Philosophically, transplantation programs can only meet defined need and optimise equity in health care if sufficient numbers of citizens value social solidarity and make an altruistic decision to donate cord blood in the public interest. Practically, cord blood banks need to have a sufficient number of CBUs to maintain human leukocyte antigen variability, so that HSCT with sufficiently high cell doses and optimal human leukocyte antigen matching is available to those who need it. 7, 8

What makes these challenges so difficult is that they reflect fundamental moral questions regarding the design and delivery of health care systems, the rights and responsibilities of citizens in liberal democracies, the commitments that we have to generational fairness, and questions concerning ownership of human tissue. While some of these ethical and legal uncertainties are specific to cord blood (due, in part, to its origins in pregnancy), others are a feature of the challenges that arise in regulating emerging tissue economies.

In Australia, cord blood banking has emerged in a regulatory vacuum, and so has come to be governed by a patchwork of common law and legislative principles, including the doctrine of informed consent, legal and ethical notions of donation, and therapeutic goods law. 9 This lack of direct regulation has undoubtedly created uncertainty regarding the status and management of cord blood and the obligations of both public and private cord blood banks.

Problems with consent: whose blood is being banked for whom?

Standard models of tissue donation assume that the process of informed consent must involve the person from whom the tissue is being taken (in living donation), or their representative (in some types of posthumous donation). Such an assumption is problematic in cord blood banking because it is not clear whether the mother or the child is the donor. As a practical matter, most collection occurs after consent from the mother either directly or on behalf of the child - but it is not clear, legally or ethically, that this is the most appropriate way of gaining consent. While consent has not yet been a subject of disagreement in this area, it is not hard to envision, in the modern era of the blended family, that there is potential for competing family claims should the therapeutic potential of cord blood materialise. And if situations arise where competing claims are made over stored cord blood, the nature of consent to storage and issues regarding proprietary interests (discussed below) will take central place in the resolution of any conflict.

Cord blood is genetically identical to the child but, depending on the method of collection and type of birth, may be collected from the mother or child, or from the cord when neither child nor mother is connected to it. There seems to be no dominant ethical or religious position as to who the donor is. 10 Nor does the law provide any direct answer, as it views the placenta/umbilicus as being part of the mother for some purposes and part of the child for others. 2 If one seeks an answer via genetics, one might argue that the child has a better claim, but it might be equally argued that other family members, including the father and siblings (both present and future), have claim to the cord blood, given the shared nature of the genetic information contained within it and its potential therapeutic uses.

We argue that these complexities require the consent process to be inclusive and representative of the different family interests in the cord blood. Thus, rather than relying purely on the birth mother to give consent, the process should, where possible, include the mother's parenting partner. Further, it is our view that the consent given by the parents should expressly recognise that they are also consenting on behalf of the child.

Questions have also been raised regarding whether informed consent to private banking is a realistic possibility, given the extremely low likelihood of requiring one's own stem cells for autologous transplantation later in life and the inevitably coercive nature of any decision that rests on assumptions about the best interests of children. It has been claimed that private banks in the United States have capitalised on the chance that families will overestimate the true likelihood of needing stored cord blood. 11 Indeed, some would argue that advertising these services is exploitative, given the degree to which expectant parents are open to consider anything that may benefit their child (irrespective of the realistic expectation of that benefit) and the low likelihood that the cord blood will ever be used. However, there is no evidence that Australian private cord blood banks have engaged in any form of misleading or deceptive conduct in relation to their services. Indeed, our own view of Australian private cord blood banks is that their advertising seems rather modest, raising notions of insurance and explicitly acknowledging the low chance of the family ever needing to access the cord blood. In any event, the strictures of the Australian Consumer Law would be likely to prevent misleading and deceptive advertising.

Cord blood banking and property rights

As tissue economies have emerged, the common law of property has changed to recognise that people have property rights over their human tissue. Traditionally, the common law refused to recognise property rights in human tissue, unless the tissue had been preserved through some work or skill. 12- 14 This rule gave the property rights to whoever provided the labour or whoever paid for it to be done, which in the cord blood context gave rights to the public banks and to the purchasers of the services of the private banks. However, in the past 2 years, courts in both the United Kingdom and Australia have begun to recognise property rights in tissue that are not dependent on the work and skill exception, giving rise to rights to its possession, use, bailment (a property relationship), and protection from negligent storage. 15- 17 These cases indicate the potential for donors to have rights to deal with their tissue under both contract and tort law.

This broader recognition of property rights is a challenge to those who see human tissue donation as a form of gift that is devoid of proprietary rights. Indeed, the very notion of a gift in law is a property relationship where property passes hands without payment. Gifts can be given without conditions attached, but property law also recognises that gifts can be made conditionally in ways that preserve some rights of control and access for the donor.

Property law may be very useful in regulating cord blood banking because it creates a language for understanding conditional donation. Property laws may help to explain how cord blood could be gifted to a public bank on the condition that the donor parent(s) have the option to withdraw donated cord blood should the donor child or their sibling require the cord blood for their own medical use, and on the condition that the family are contacted before the cord blood is used in treatment or research (which is standard practice in some public banks). Property law also provides a model for understanding how, in the private banking context, a relative (such as a grandparent) could pay for the banking on the grounds that it is made available to a range of family members through a form of discretionary trust.

We believe that the current practice in the private banking industry has already effectively adopted property forms. The contracts for storage are bailments. The contracts also treat the cord blood as being held on behalf of an individual child or on behalf of the family group. This idea of holding property for the benefit of another is clearly a trust, where the legal title (held normally by the parents) is exercised for the benefit of the child (or family group). Once the child turns 18 years of age, most Australian contracts then state that the property then passes to the (now adult) child, which is again a classic trust mechanism.

In public banking, there appears to be more reticence to adopt property language, arguably because of its non-commercial focus. We argue that a public bank works just like a charitable trust - holding valuable property for the public benefit in pursuit of the charitable aims of improved health care. The usefulness of charitable trust laws is that they create a framework for donation and use of the cord blood.

While we recognise that property law is not a panacea for all regulatory woes, it does have the potential to provide tools for unpacking cord blood banking, as it provides a well established mechanism for recognising rights and resolving disputes between different interest holders.

Private, public or hybrid banking?

The complex issues surrounding cord blood banking and donation are not simply a function of the uncertain legal status of cord blood; they are also a function of the structure and function of public and private banks. Traditionally, public banks have stored donated cord blood for public use in allogeneic transplant programs and some (limited) types of research, while private banks have focused on storage for autologous treatment for the child donor. However, the line between public and private banking is becoming increasingly blurred. 5 Many private banks now offer cord blood to matched family members of the child and are becoming increasingly involved in research projects. Public cord blood banks have generally acceded to requests to release donated CBUs for autologous transplantation or for use in related donor transplantation. But although there has been some convergence of practice, requests to use CBUs that have been donated to public banks to support allogeneic transplantation programs for research are more challenging. 18

While those with opposing perspectives often build walls to protect their interests, this is unlikely to provide the best approach to accommodating both public and personal interest in cord blood. Indeed, the tensions that currently exist are likely to increase if the indications for autologous transplantation expand, or if evidence emerges that cord blood stem cells may have a therapeutic role outside of transplantation - be that in regenerative medicine or in immunoprotection against non-communicable diseases. As Han and Craig point out in this issue of the Journal, 18 it is becoming increasingly clear that policy is needed to deal with requests for the release of cord blood for therapeutic and research purposes from public banks. Serious consideration needs to be given to hybrid models of banking that offer both public donation and private banking or make privately stored CBUs available to the public system should they be needed for transplantation. 5

Conclusion

Cord blood banking is a challenging area to regulate. It throws up unique problems of consent and is complicated by a dual system of public and private banking. The emergence of property rights in human tissue is a further complication, but one that we feel will ultimately provide a means of untying some of these difficult questions and resolving the disputes that will inevitably arise concerning this valuable resource. Regardless of the way forward, it is clear that any regulation should be developed in an open and transparent manner. Regulation should be drafted in light of the concerns of both public and private banking and should be based on well informed public debate. We welcome efforts by AusCord and the Australian Bone Marrow Donor Registry to address these issues and believe that there is much to be gained from a broader public discussion about the goals of medicine and research and the importance of community and social solidarity.

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Ethical and legal issues raised by cord blood banking - the challenges of the new bioeconomy

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While human tissue has always had cultural, educational and scientific value, it is only in the past 40 years that tissue economies have begun to emerge. 1 These economies have been driven by advances in technology that rapidly reversed our perception of human tissue as a useless by-product of treatment, to being a valuable and powerful source of wealth.

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Mouse models of spinal cord injury and stem cell transplantation

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Spinal cord injury is one of the most devastating neurologic conditions that mostly affects young, and otherwise healthy, patients. Following the prim...

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In 2013, the world's first lab-grown burger was unveiled to the world. It carried a $US330,000 price tag, and apparently, it wasn't all that tasty. But the scientists behind the idea have been hard at work, and artificial meat that's both cost-effective and palatable may arrive sooner than we think.

It's not just cow-free beef burgers on the future menu - several groups around the world are attempting to clone chicken breasts and fish fillets, as well. Why do scientists want to grow meat in vats instead of on animals, and how close are we to actually accomplishing it?

The Big Resource Hog

The arguments for growing so-called 'cultured' meat are as wide-ranging as the reasons people decide to become vegetarian or vegan. If you're not vegetarian or vegan, you've probably received a mouthful on this subject from a friend or family member before, so I'm going to keep it brief and focus on the argument cultured meat proponents seem to embrace the most: Sustainability.
Literally hogging our resources. Picture: Wikimedia
The meat industry is a huge contributor to humanity's environmental footprint, accounting for some 18% of our total greenhouse gas emissions. And that number's deceptively low, because it includes roughly 40% of methane and 65% of nitrous oxide emissions, which are respectively 23 and nearly 300 times more potent climate warming agents than carbon dioxide. What's more, the environmental footprint of livestock production is growing fast. By 2050, global meat production is projected to double from its 1999 levels, according to the FAO. At that time, the FAO writes, "The environmental impact per unit livestock must be cut by half, just to avoid increasing the level of damage beyond its present level."

If climate arguments aren't your MO, try this one on for size: Animal agriculture is soaking up an enormous portion of our arable land, drinkable water, edible food and combustible fossil fuel resources. According to a study published in the American Journal of Clinical Nutrition, livestock in the US consume more than 7 times as much grain as the American population - enough grain to feed about 840 million people. The same study finds that roughly 25 kilocalories of fossil fuel energy are consumed for every 1 kilocalorie of meat protein produced, compared with a 2.2:1 ratio for corn. And producing 1 kg of animal protein requires 100 times more water than 1 kg of grain protein, in part because we have to take the water used to grow the animals' food into account. You can read the full report for additional statistics, but you'll find that on nearly every measure, raising livestock takes a lot more resources per calorie out than growing edible plants does.

Since we don't have industrial, meat-producing labs yet, it's hard to say how the environmental impact and resource cost of cultured meat will measure up. But there's reason to be optimistic. Here's what a life-cycle assessment study, published in Environmental Science and Technology in 2011 found:

The results showed that production of 1000 kg cultured meat requires 26 - 33 GJ energy, 367 - 521 m ³ water, 190 - 230 m ² land, and emits 1900 - 2240 kg CO ₂-eq GHG emissions. In comparison to conventionally produced European meat, cultured meat involves approximately 7 - 45% lower energy use (only poultry has lower energy use), 78 - 96% lower GHG emissions, 99% lower land use, and 82 - 96% lower water use depending on the product compared. Despite high uncertainty, it is concluded that the overall environmental impacts of cultured meat production are substantially lower than those of conventionally produced meat.

"This actually makes a lot of sense," Shier Friedman, co-founder of the pro-cultured meat Modern Agriculture Foundation told me over the phone. "When we're raising animals, a very large amount is being discarded: The bones, fur, eyeballs, organs. What we're doing is wasting resources to produce stuff that we don't get back. With cultured meat, you grow exactly what you want, and you barely throw anything away."

That all sounds promising, but in reality, cultured meat will only save us resources and reduce the meat industry's environmental footprint if we can produce the stuff at economies of scale. The meat growers of the future are dreaming big, but the scientific and engineering challenges ahead are also enormous.

The Quarter Pounder with Stem Cells
The most expensive burger ever grown. Picture: David Parry / PA Wire
Two years ago, physiologist Mark Post of the University of Maastrich unveiled the world's first cultured beef burger, assembled in his lab from thousands of individual strands of muscle tissue. It precipitated an international media blitz: Hundreds of news articles, radio podcasts, and prime-time TV minutes were devoted to Unveiling of The Burger. But as for the flavour? A bit lacklustre, according to food scientist Hanni Rützler and journalist Josh Schonwald, the two chosen tasters. As NPR reported at the time:

"The texture, the mouthfeel has a feel like meat," Schonwald put it. "The absence is ... fat. It's a leanness. But the bite feels like a conventional hamburger. It's kind of an unnatural experience [without condiments]."

Rützler agreed the burger was edible, but not delectable. "It has quite some intense taste, it's close to meat," she said. "I thought it would be softer."

Still, one can argue the demonstration was less about the meat's flavour and more about what scientists had managed to accomplish. Over the course of three months, Post's lab turned a handful of stem cells extracted from a cow's shoulder into a patty consisting of 20,000 individual muscle fibres. Keeping those cells healthy, well-fed and contamination-free during their growth was no small feat - in fact, it's something biomedical engineers in the artificial tissue business have been struggling to do for over a decade.

But with a $US300,000 price tag and a mediocre review, Post knew he had to do better. He's spent the last two years refining the process, and I caught up with him over the phone to hear how it's been going.

One of the big takeaways from the 2013 cultured burger demo was that meat just ain't right without fat. So, Post's lab is now culturing fatty tissue in addition to muscle fibres. Working out that process has taken some time. Until now, there hasn't been a whole lot of scientific interest in culturing fat cells, and methods that did exist used chemicals we don't really want to be eating.

"The original methodology to make fat cells from stem cells requires steroids, which are not wanted in food applications," Post told me. "We had to redesign that and work with the biochemistry of the cell to figure out which stimuli we should use. We now have a bunch of natural components of fat that actually stimulate fat production."

Right now, Post's lab is culturing beef fat and muscle tissue separately, and mixing the two after the fact. In the future, Post imagines combining the two cell types in a co-culture. But first, there are a couple other burger basics the team is trying to improve on.

For one, Post would like to eliminate the use of animal products (stem cells aside, obviously) from the culturing process. In laboratories, cells are often grown using a foetal bovine serum extracted from unborn calves. But from a sustainability point of view, juicing a baby cow to grow a burger is less than ideal. It also doesn't do much for cultured beef's image as a cruelty-free product. And, while it may be an unlikely scenario, a disease-contaminated batch of foetal bovine serum could spell disaster. Better off, Post says, if we could work out an animal-free culture serum - one based on photosynthetic algae or cyanobacteria, perhaps.
Mark Post and The Burger. Picture: David Parry / PA Wire
Another technical issue Post's team is trying to sort out how to boost cultured beef's iron content. In muscle tissue, iron is found primarily inside an iron and oxygen-binding protein known as myoglobin. But because lab-grown meat lacks a circulatory system, it's kept in a very high-oxygen environment, which has the unintended consequence of reducing cellular myoglobin expression. Less myoglobin means less iron, poorer nutritional content and a weaker flavour.

Once Post is satisfied with cultured beef version 2.0 - a fattier, more iron-rich and animal-free substance than its predecessor - he'll start thinking about scaling up. Going from petri dishes to factories raises a host of new issues. For one, there's that oxygen problem again: Without a circulatory system and blood vessels to shuttle O2 around, we can really only ever hope to grow thin sheets of meat. Post wouldn't get into specifics about the technologies involved in scaling this process up, other than hinting that 3D printers and new types of scaffolding materials might be involved.

In the cultured meat facilities of the future, impeccable cleanliness will be another top priority. Keeping everything sterile will no doubt up the maintenance costs, but Post sees it as a worthy challenge. That's because, if we can ensure truly sterile production conditions, we might be able remove antibiotics from the equation.

"Currently, we only use antibiotics in the first stage of the process where we harvest cells from the animals," Post said. "That's not 100% sterile. But if you get rid of the serum, it's much easier to get rid of the antibiotics. We're using very stringent doses now, but I think in the future antibiotics can be eliminated entirely."

Today, most of the antibiotics produced in America are guzzled down by livestock living in filthy, overcrowded conditions. Reducing our dependency on antibiotics in animal agriculture will slow the spread of antibiotic resistant bacteria and ensure that our medicines last for future generations of humans. (We really do not want to live in a post-antibiotic future.)

As for the public's reaction to encountering lab-grown beef in the grocery stores? That's something Post spends a lot of time thinking about.

"You do hear people making references to GMOs, playing God, and 'frankenfoods' - that sort of thing," Post told me. (Despite public perception, cultured beef is not a genetically modified food, nor are genetically modified foods evil.) "It's hard because these are emotional reactions - there's usually no rationale behind them."

"But," he continued, "We find that when we do surveys and explain what it is that we're doing, the reactions tend to be more positive."

In Post's mind, a more legitimate concern than 'frankenfood' is the possibility of small farmers losing control of the meat production system entirely (to be fair, they have already been largely hedged out in the United States.)

"That's something we have to address," Post said. "Can you design ways of implement culturing beef on a small scale so that it becomes a community thing? Can you design a home meat maker?"

But Post reckons we're still ten or twenty years away from producing cultured beef en masse. Right now, growing a burger that's just as mouth-wateringly juicy and flavourful as a natural beef patty - and figuring out how to scale up - is keeping the our cultured beef-makers plenty busy.

Fish and Chicken
Picture: New Harvest. org
An affordable, scaleable cultured beef industry would go a long way toward reducing humanity's environmental footprint. But Post isn't the only scientist trying to cook up meat in the lab. In fact, way back in 2002, a NASA-funded team demonstrated it was possible to grow fish filets outside of a fish. Admittedly, this early effort was a bit grisly: The team cut chunks of muscle tissue from freshly slaughtered goldfish and dunked them in a culture fluid for a week. The tissue chunks grew by over 14 per cent, which lead scientist Morris Benjaminson attributed to partially differentiated myoblast cells dividing to make more of themselves.

Goldfish filets never caught on, but Post tells me that a few other research teams have recently begun investigating cultured seafood again, presumably using more modern techniques. Meanwhile, the Modern Agriculture Foundation has taken up the lab-grown chicken challenge. In some ways, that effort is even more ambitious than Post's stem cell burger. Rather than growing a handful of individual cell types, Friedman's foundation is hoping to clone entire chicken breasts - complex, 3-dimensional organs.

"We wanted to do something big, something that is needed, something that is important and could literally change the food culture in the world," Frieman told me. "We knew a group was already doing beef, so we decided to go with another of the most popular food animals in the world."

So far, Future Meat - the MAF's cultured chicken research program - has only conducted feasibility studies, looking at the costs, time and ingredients associated with growing whole chicken breasts in vats. There are some parallels to the burger meat effort: For instance, Future Meat's lead researcher Amit Gefen told in an email that his team is very interested in coming up with a veggie-based culture medium that would eliminate animal serum from the production process.

But in many ways, Future Meat's goal is very different from that of the Post lab. Engineering 3D-organs means thinking about how different cell types will interact, and how to coax tissues into taking on a certain size and shape. It also means worrying a lot about oxygen and nutrient availability. While some tissue engineers are trying to develop synthetic capillary networks for artificial organs, Gefen is hoping Future Meat can avoid that additional complexity with a cleverly designed bioreactor.

"I expect that developing a capillary network to feed the construct would be too complicated and expensive for the purpose of creating a food product, and so other approaches should be adopted," Gefen told me. "The most feasible one appears to be developing a special bioreactor that will circulate nutrients in the scaffolds (with seeded cells) efficiently so that cells will be able to proliferate and grow on the scaffolds."

Gefen envisions his bioreactors will have the ability to stimulate growing muscle tissue, either mechanically or electrically, to facilitate proper development. Again, this is all very conceptual right now, but with more PhD student labour and grant funding, Future Meat is hoping to make headway on bioreactor prototypes within the next several years.

The Road Ahead

Cultured meat still has a long way to go, but it's exciting to see groups of scientists around the world taking up the challenge. And in a very short amount of time, we've seen major progress. This past April, Post announced that his team has managed to cut the cost of cultured beef to just $US80 per kilogram, or roughly $US11 per burger. That's a pretty stunning price drop, considering two years ago one of his burgers could've financed a med student's education.
Hey, one can dream. Picture: Harald Groven / Flickr
As public awareness of cultured meat grows, proponents like Friedman and Post seem hopeful that their products will, one day, become just as acceptable as meat grown on animals - perhaps even more so.

"We're trying to find a realistic way to produce the same type of food we love to eat," Friedman said. "Eventually cultured meat will be cheaper and more sustainable. And we'll have so many people on the planet that there just won't be another option. The human race is progressing, technology is progressing, and eventually, people are going to get used to this idea."

Personally, I'm looking forward to the day when I can order a cultured salmon roll without wondering if my fish was sustainably harvested, or a McDonald's quarter pounder without imagining the sorry life of the animal it came from. Bring it on, science.
Picture: David Parry / PA Wire

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The Future Will Be Full Of Lab-Grown Meat

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In 2013, the world's first lab-grown burger was unveiled to the world. It carried a $US330,000 price tag, and apparently, it wasn't all that tasty. But the scientists behind the idea have been hard at work, and artificial meat that's both cost-effective and palatable may arrive sooner than we think....

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Catalyst: Corneal Stem Cells - ABC TV Science

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NARRATION The cornea is like the window of the eye, but sometimes that window loses clarity. Dr Stephanie Watson The cornea has a very unique architecture to ensure that it remains transparent. And so when that architecture is disrupted such as in stem cell failure it becomes hazy.

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Given the chance to freeze their newborn's own stem cells, more and more expectant parents are signing up with pricey cord-blood banks. But could these cells really save your child's life someday?

Insurance -- or Reassurance?

When Tracey and Victor Dones's 4-month-old son was diagnosed with osteopetrosis, a potentially fatal disorder that affects bone formation, the panic-stricken couple was relieved to hear that a stem-cell transplant could save his life. "We'd paid to store Anthony's umbilical- cord blood in a private bank in case he ever needed it -- and I thought we were so smart for having had the foresight to do that," says Tracey.

The Doneses were shocked, however, when doctors told them that Anthony's cord blood couldn't be used because the cells contained the same genetic defect that caused his condition. "The materials provided by the bank said this was Anthony's life insurance and could save him if he needed it. They never mentioned that the cells could be diseased. We felt duped," Tracey says. The Long Island, New York, couple has since filed a lawsuit against the bank alleging false advertising and consumer fraud.

Is It Right for Your Family?

Once considered medical waste, the blood left in the umbilical cord after a baby's delivery is now known to be a rich source of stem cells similar to those in bone marrow. It's been used in transplants to treat more than 70 different diseases including leukemia, lymphoma, sickle-cell disease, and some metabolic disorders. Unlike with marrow, which is obtained through a painful medical procedure and replenished by the body, there's only one chance to collect this seemingly magical elixir: immediately after a baby's birth.

Since the first successful sibling-to-sibling cord-blood stem-cell transplant was performed in 1988 to treat a genetic disorder called Fanconi's anemia, more than 20 private banks have opened. And they seem to have the address of every expectant couple in America -- whose mailboxes bulge with brochures encouraging them to take advantage of this once-in-a-lifetime opportunity. "Cord-blood banking is like insurance to protect your family against unforeseeable events," says Stephen Grant, cofounder and senior vice president of Cord Blood Registry, a large California-based private bank. "You do it out of love and responsibility for your family. Sure, you hope you'll never have to use the blood, but if you do, it'll be there."

Not surprisingly, this emotional pitch is working -- especially because the seemingly unlimited potential of stem cells has dominated the news in recent years. From 2003 to 2004, for example, the number of couples opting to use a private bank increased by 55 percent to 271,000. The three biggest companies -- who have the majority of the approximately $250 million market -- are vying for business.

Like any insurance, cord-blood banking isn't cheap. Banks initially charge from $1,000 to $2,000 to collect and process the stem-cell units, which are stored for a family's exclusive use. When you factor in additional costs for shipping (about $150 for a medical courier), the doctor's collection fee (prices can range from $150 to $500), and annual storage fees averaging $100 per year for 18 years, parents can expect to pay up to $4,000 in expenses not covered by insurance.

Certainly, there are plenty of doctors who have high hopes for stem-cell advances and advise patients to consider cord-blood banking. When private banks first started sending him informational packets, Jordan Perlow, MD, a maternal-fetal specialist in Phoenix, assumed they were just trying to profit from parents' anxieties. But after attending medical conferences and scrutinizing studies about developments in stem-cell therapies, Dr. Perlow now encourages his patients to privately bank if they can afford it because he's convinced that it might save their child's life or the life of another family member. "If private banking had been available when my children were born, I would have done it," he says.

There are no hard numbers on a child's risk of needing a stem-cell transplant: It's anywhere between one in 1,000 and one in 200,000, according to studies cited by ACOG and the AAP. But private banks' marketing materials often place the odds at one in 2,700 and note that these numbers don't factor in its potential future use for diabetes, Alzheimer's, Parkinson's disease, and spinal-cord injuries in adults. "Researchers are constantly discovering new treatments using stem cells," says Gerald Maass, executive vice president of corporate development for Cryo-Cell, a private bank in Clearwater, Florida. Another major bank's Web site claims incredible odds: "Should cord blood prove successful in treating heart disease, the lifetime probability of being diagnosed with a disease treatable by cord blood will increase from one in 100 to one in two."

What Banks Don't Tell Parents

While cord-blood companies herald the possible future treatments of many adult diseases with stem cells, they rarely mention a key issue. Researchers have greater hopes for the potential of embryonic stem cells, which are thought to have the ability to develop into many different types of cells. It is not known whether the stem cells in cord blood have that ability; until recently, it was thought that they (like those in bone marrow) could only regenerate blood and immune cells.

What's more, few cord-blood transplants have been given to adults because most units haven't contained enough stem cells to treat anyone weighing more than 90 pounds, says Joanne Kurtzberg, MD, program director of the division of pediatric blood and marrow transplantation at Duke University Medical Center. And since the procedure is relatively new, no one knows how many years the frozen units will remain viable.

In fact, the shocking truth is that the majority of all cord blood stored in private banks may be unusable. Approximately 75 percent of the units donated to public banks are discarded or used in research because they don't contain enough stem cells for transplants, says Mary Halet, manager of cord-blood operations for the Center for Cord Blood at the National Marrow Donor Program, a Minneapolis-based nonprofit organization that maintains the nation's largest public supply of cord blood. Yet private banks store every unit they collect, which means that you might pay to store blood that won't be usable if you need it years later.

And as Victor and Tracey Dones learned, a child's own cord blood can't always be used to treat him, even when he's young. "Childhood leukemia is one of the diseases private banks like to play up, but most kids with leukemia are cured with chemotherapy alone. If a transplant is needed, we wouldn't use a child's tainted cord blood," Dr. Kurtzberg says.

In fact, the AAP does encourage parents to keep their child's cord blood if a family member has already been diagnosed with a stem-cell-treatable disease. But a family won't have to foot the bill: The Children's Hospital Oakland Research Institute, in California, will bank a baby's cord blood for free if a family member needs it at the time of the baby's birth. Some private banks, such as Cord Blood Registry, Cryo-Cell, and ViaCord, have similar programs.

In 2007, the AAP issued a revised cord-blood-banking policy, that discourages private banks for families who aren't already facing a health crisis. "These banks prey on parents' fears of the unknown, and there's no scientific basis for a number of medical claims they make," says Bertram Lubin, MD, president and director of medical research for Children's Hospital Oakland Research Institute, and coauthor for the AAP's 2006 cord-blood-banking committee.

The Promise of Public Banking

Even if a sick child has a sibling donor, there's only a 25 percent chance that cord blood will be a perfect match -- and an equal chance it won't match at all. That's why public donations are so important. So far, many more stem-cell transplants have been done using cord blood stored in public banks. From 2000 to 2004, more than 2,200 unrelated transplants were done nationwide.

"One of the wonderful things about cord blood is that unlike bone marrow, you don't always need a perfect match in order for it to work," says Dr. Kurtzberg, who performed the first unrelated cord-blood transplant in the U.S. And it was a public donation that ultimately saved Anthony Dones. Within a week of starting a search, the National Cord Blood Program, a public bank operated by the New York Blood Center, found a "close enough" match. Had the now-3-year-old been forced to rely on a bone-marrow match, he might still be waiting.

Fortunately, those odds should improve soon. In 2005, Congress passed the Stem Cell Therapeutic and Research Act, which provides $79 million in federal funding to create a centralized cord-blood registry much like the one that exists for bone marrow. The goal is to expand the existing inventory of 45,000 donated cord-blood units to 150,000.

Of course, this means that expectant parents will have one more choice to make about their child's health and future. "I certainly don't think parents should feel guilty if they don't privately bank their child's blood," Dr. Kurtzberg says. The best choice is the one that works for your family.

7 Smart Questions to Ask a Cord-Blood Bank

Obviously, price and a compelling Web site aren't the only factors to consider when choosing a bank. Be sure to do your homework before signing up.

1. Is the facility accredited by the American Association of Blood Banks? This means its labs, banks, and procedures meet set standards.

2. How long has the company been in business? At least five years is best.

3. How many units does it store? Look for a bank that has thousands.

4. How many successful transplants have been performed with its stored samples? Having at least one demonstrates that its process works, but two or three is better.

5. Is the blood stored as a single unit or in several samples? Freezing in portions is preferred so the blood can be tested for potential transplant use without thawing -- and wasting -- the entire sample.

6. Is the company private or publicly held? If it's a publicly traded company, you'll have the advantage of reviewing its financials. Many banks are part of larger biotech companies.

7. Is the storage fee fixed or subject to increases? You want to know the total price tag up front.

All content here, including advice from doctors and other health professionals, should be considered as opinion only. Always seek the direct advice of your own doctor in connection with any questions or issues you may have regarding your own health or the health of others.

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Given the chance to freeze their newborn's own stem cells, more and more expectant parents are signing up with pricey cord-blood banks. But could these cells really save your child's life someday? When Tracey and Victor Dones's 4-month-old son was diagnosed with osteopetrosis, a potentially fatal disorder that affects bone formation, the panic-stricken couple was relieved to hear that a stem-cell transplant could save his life.

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Published online 4 September 2011 | Nature | doi:10.1038/news.2011.517

News

Scientists have made reprogrammed stem cells from an endangered rhinoceros and a monkey.

Cells from the northern white rhino Fatu (left) have been converted into stem cells and put into storage.M. Cizek/AFP/Getty Images

Fatu, a female northern white rhinoceros who lives in a Kenyan conservation park, is one of just seven of her kind left in the world. But millions of her stem cells, stored in a freezer in California, might one day help boost her population's ranks.

The northern white rhino (Ceratotherium simum cottoni) and another animal facing extinction, the drill monkey (Mandrillus leucophaeus), have become the first endangered animals to have their cells transformed into stem cells like those found in early embryos. These cells can be stored and multiplied in culture, and are theoretically capable of making any tissue in the body - including sperm cells that could be used in assisted captive breeding programmes. The work is published online today in Nature Methods.

About five years ago, Jeanne Loring, a stem-cell biologist at the Scripps Research Institute in La Jolla, California, was contacted by Oliver Ryder, a scientist at the nearby San Diego Zoo, who was keen to collect stem cells from endangered animals. Obtaining stem cells by sacrificing the fertilized embryo of an endangered species was out of the question, so Loring tried to think of other sources, but came up empty. "The prospect of getting bone marrow stem cells from a rhinoceros was kind of daunting," she says.

A couple of years later, in 2007, teams at the University of Kyoto in Japan and the University of Wisconsin in Madison, revealed that the cells called fibroblasts from human connective tissue could be coaxed into a state resembling that of an embryonic stem cell by activating a suite of reprogramming genes in the adult cells,. Ryder's team had been preserving fibroblasts from endangered animals since the 1970s as part of a project called the Frozen Zoo, so the cell-reprogramming technology seemed like a good way to create stem cells from endangered animals, Loring says.

As a proof-of-principle experiment, Ryder gave Loring cells from Fatu and from a captive male drill monkey named Loon (who has since died). Drills are now found in the wild only in tiny pockets of western Africa, their numbers dwindling because of habitat loss and a thriving bushmeat trade.

Loring and her colleague Inbar Friedrich Ben-Nun at first assumed that human versions of the reprogramming genes would not convert rhino or drill fibroblasts to stem cells, so the team tried reprogramming the drill cells with genes from another monkey species, the rhesus macaque, and Fatu's fibroblasts with horse genes. Both attempts failed.

Reprogramming success

To Loring's surprise, however, the corresponding human genes did transform both animals' cells into embryonic-like stem cells called induced pluripotent stem cells (iPS cells). As proof of pluripotency, the researchers coaxed the drill and rhino iPS cells into making the three different kinds of simple tissues that produce all the other tissues in the body.

Loring does not plan to use the iPS cells of Fatu and of Loon to clone these individuals. Instead, the cells could be converted into germ cells for use in assisted breeding programmes to help diversify the gene pools of endangered species, she says. Healthy mice have been born this way, and Loring believes that, in time, the techniques will be made to work with other animals. "If everything falls into place and everything works, there is a way to generate new animals," she says.

"I think this is a very exciting development," says Robert Lanza, chief scientific officer of Advanced Cell Technology, based in Santa Monica, California, and part of a team that carried out the first cloning of an endangered animal, a guar bull named Noah, in 2000. When human iPS cells were first described, Lanza touted their potential for endangered species conservation in a letter to the journal Science, and he has even patented a technique to clone endangered animals from iPS cells, which he says he would license freely for conservation efforts.

No quick fix

William Holt, a reproductive biologist at the Zoological Society of London, is involved in a collaboration called the Frozen Ark, based at the University of Nottingham, UK, which culls DNA and cells from endangered animals. He doubts that iPS cells will save many threatened species, particularly those already on the brink of extinction like the northern white rhinoceros.

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"To be honest I think it's a bit of a stunt," he says. Scientists know little about the reproductive biology of these animals, which is needed to support assisted reproduction programmes, and, with so few individuals remaining, there is little opportunity to learn more, he says.

Loring concedes that there are technological gaps to fill in before iPS cells can help save species. "I don't know how you could super-ovulate a rhino," she says. But she dismisses the notion that iPS cells from endangered animals are a gimmick. Even if the technologies to use them in assisted breeding aren't mature, the cells offer a way to preserve the genetic diversity of individual animals long after they have died.

Fatu, at least, isn't waiting for such breakthroughs: in January this year, she began mating with a male named Suni.

Commenting is now closed.

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Could stem cells rescue an endangered species?

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Published online 4 September 2011 | Nature | doi:10.1038/news.2011.517 News Scientists have made reprogrammed stem cells from an endangered rhinoceros and a monkey. Cells from the northern white rhino Fatu (left) have been converted into stem cells and put into storage.M.

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GMO processes

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Are GMOs Good or Bad? Genetic Engineering & Our Food

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By administering a combination of three genes, researchers have managed to convert one type of adult mouse cell into another type. The new approach builds on information gleaned from developmental studies of embryonic stem cells (see story #16) and one day may be used to create healthy replacements for harmed or diseased tissue.

Douglas Melton, codirector of the Harvard Stem Cell Institute in Cambridge, Massachusetts, and his colleagues study both the stem cells that develop into the pancreas and its insulin-producing cells and the genes that guide those cells' development.

Instead of trying to coax stem cells to differentiate into pancreatic cells, Melton focused on identifying transcription factors, proteins that bind to DNA and turn genes on and off. He and his collaborators found that three transcription factors, when targeted to the pancreas of a living mouse, converted fully formed, non-insulin-producing pancreatic cells into cells that were functionally identical to insulin-producing cells-no stem cells required.

Melton believes that this direct reprogramming could eventually be used to help stimulate insulin production in people with type 2 diabetes or could even be applied to neurodegenerative and cardiovascular diseases.

"Why should you have to take a cell and turn it all the way back to the beginning, erase all its memory, when you are still left with the problem of telling it how to become a new type of cell?" Melton asks.

"I like to think of this as a new way of providing cells in regenerative medicine."

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#17: Cell Reprogramming Could Help Cure Diabetes-and Other Diseases

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By administering a combination of three genes, researchers have managed to convert one type of adult mouse cell into another type. The new approach builds on information gleaned from developmental studies of embryonic stem cells (see story #16) and one day may be used to create healthy replacements for harmed or diseased tissue.

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Scripps Research scientists produce first stem cells from endangered species. Cells could make it possible to improve reproduction and genetic diversity for some species, possibly saving them from extinction, or to bolster the health of endangered animals in captivity.

Credit: San Diego Zoo

Stem cells are quickly becoming an important tool for human medical treatments, and researchers are betting they will also be a useful tool for zoo animals. They are working to create stem cell lines from zoo animals, for use in treating animal diabetes and other ailments as well as helping the animals reproduce.

The scientists have already created a "frozen zoo," which contains different types of cells from every animal there, and now they are putting together a "stem cell zoo."

"There are only two animals in it," study researcher Inbar Friedrich Ben-Nun, of The Scripps Research Institute, said in a statement, "but we have the start of a new zoo, the stem cell zoo."

Stem cells are prized, because they can be turned into any type of cell in the body, a characteristic called pluripotency. The cells can even be turned into sperm or egg cells, and used in assisted reproduction to make more individuals of the species.

"The most important thing is to provide these stem cells as a resource for other people taking some of the next steps," said Jeanne Loring, also of The Scripps Research Institute.

Endangered stem cells

The researchers started with two species: the drill primate, a highly endangered primate genetically close to humans, and the northern white rhinoceros, which is genetically far from humans and also incredibly endangered.

To create the stem cells, the researchers used the same genes that are used to turn human cells pluripotent; they inserted those genes into the animals' skin cells. They had originally tried to use genes from the animals themselves and their close relatives, but after more than a year of trying they were having little success.

The new technique isn't very efficient yet, transforming just a few cells into stem cells at a time, but that's enough, the researchers said.

Stem cell therapies

Both animals, the researchers said, were chosen because they could benefit from stem cells now. For instance, the drill primate suffers from diabetes when in captivity, and stem cell-based treatments for diabetes being researched in humans suggest the same may work in these primates.

The rhinoceros was chosen because it is one of the most highly endangered species on the planet, with only seven animals, all in captivity, in existence (two of which are in the San Diego Zoo Safari Park). They haven't reproduced in several years, and because the population is so small there is a lack of genetic diversity, which could affect their survival.

If the researchers can use the stem cells to make sperm and eggs from skin cells of deceased animals in the frozen zoo, they could reintroduce some genetic diversity into the population, while also increasing its size.

"The best way to manage extinctions is to preserve species and their habitats," study researcher Oliver Ryder, of the San Diego Zoo, said in a statement. "But that's not working all the time."

The rhinos are a perfect example, he said, because there are so few. "Stem cell technology provides some level of hope that they won't have to become extinct even though they've been completely eliminated from their habitats."

The study was published today (Sept. 4) in the journal Nature Methods.

You can follow LiveScience staff writer Jennifer Welsh on Twitter @microbelover. Follow LiveScience for the latest in science news and discoveries on Twitter @livescience and on .

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'Stem Cell Zoo' May Aid Endangered Species

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Stem cells are quickly becoming an important tool for human medical treatments, and researchers are betting they will also be a useful tool for zoo animals. They are working to create stem cell lines from zoo animals, for use in treating animal diabetes and other ailments as well as helping the animals reproduce.

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Mitochondrial disease - children with 3 parents

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Mitochondrial disease - children with 3 parents

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Alana Saarinen loves playing golf and the piano, listening to music and hanging out with friends. In those respects, she's like many teenagers around the world. Except she's not, because every cell in Alana's body isn't like mine and yours - Alana is one of a few people in the world who have DNA from three people.

"A lot of people say I have facial features from my mum, my eyes look like my dad... I have some traits from them and my personality is the same too," says Alana.

"I also have DNA from a third lady. But I wouldn't consider her a third parent, I just have some of her mitochondria."

Mitochondria are often called the cell's factories. They are the bits that create the energy all of our cells need to work, and keep the body functioning. But they also contain a little bit of DNA.

Alana Saarinen is one of only 30 to 50 people in the world who have some mitochondria, and therefore a bit of DNA, from a third person. She was conceived through a pioneering infertility treatment in the USA which was later banned.

But soon there could be more people like Alana, with three genetic parents, because the UK is looking to legalise a new, similar technique which would use a donor's mitochondria to try to eliminate debilitating genetic diseases. It is called mitochondrial replacement and if Parliament votes to let this happen, the UK would become the only country in the world to allow children with three people's DNA to be born.

The structure of a cell

Nucleus: Where the majority of our DNA is held - this determines how we look and our personality

Mitochondria: Often described as the cell's factories, these create the energy to make the cell function

Cytoplasm: The jelly like substance that contains the nucleus and mitochondria

Alana was born through an infertility treatment called cytoplasmic transfer.

Her mum, Sharon Saarinen, had been trying to have a baby for 10 years through numerous IVF procedures.

"I felt worthless. I felt guilty that I couldn't give my husband a child. When you want a biological child but you can't have one, you're distraught. You can't sleep, it's 24-7, constantly on your mind," she says.

Cytoplasmic transfer was pioneered in the late 1990s by a clinical embryologist Dr Jacques Cohen and his team at the St Barnabus Institute in New Jersey, US.

"We felt that there was a chance that there was some element, some structure in the cytoplasm that didn't function optimally. One of the major candidates that could have been involved here are structures called mitochondria," he says.

Cohen transferred a bit of a donor woman's cytoplasm, containing mitochondria, to Sharon Saarinen's egg. It was then fertilised with her husband's sperm. As a little bit of mitochondria was transferred, some DNA from the donor was in the embryo.

Seventeen babies were born at Cohen's clinic, as a result of cytoplasmic transfer, who could have had DNA from three people.

But there was concern about some of the babies.

"There was one early miscarriage, considering there were twelve pregnancies that is an expected number," says Cohen.

He and his team believed that miscarriage occurred because the foetus was missing an X chromosome.

"Then there was another twin pregnancy, where one [of the twins] was considered entirely normal and the other had a missing X chromosome.

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"So that's two out of the small group of foetuses that was obtained from this procedure. This did worry us and we reported that in the literature and in our ethical and review board that oversees these procedures," he says.

At the time of birth, the other babies were all fine. A year or two later, another of the children was found to have "early signs of pervasive early developmental disorder which is a range of cognitive diseases which also includes autism." Cohen told me.

He says it's difficult to know if the abnormalities happened by chance or because of the procedure.

Other clinics copied the technique and Cohen estimates that around 30 to 50 children worldwide were born who could have DNA from three people as a result.

But in 2002 the American regulator, the FDA (Food and Drug Administration) asked clinics to stop doing cytoplasmic transfer due to safety and ethical concerns. All of them did.

"There was a reaction from scientists, ethicists, the public at large, I think most of it was supportive, some of it was critical - I think this is normal, every time an experiment is done in medicine there is a reaction - what are the risks here?" says Cohen.

At the time, some were concerned because they felt this was germ line genetic modification. What "germ line" means is that a child like Alana would pass her unusual genetic code down to her children. And their children, would pass it to their children and so on.

Because we inherit our mitochondria only from our mothers, only female children would pass their unusual genetic code on. Crossing the germ line as it is known has never been done before so very little is known about what the outcome could be.

Due to a lack of funding, Cohen says, it hasn't been possible to find out about how any of the children like Alana who were born from cytoplasmic transfer are doing. But the St Barnabus Institute is now starting a follow up study to check their progress.

Sharon Saarinen says her daughter Alana is a healthy, typical teenager

"I couldn't ask for a better child. She is an intelligent, beautiful girl inside and out, she loves math and science ... she does really well in school. She helps me around the house... when she's not texting!"

"She has always been healthy. Never anything more than a basic cold, or a flu every now and then. No health problems at all."

The health of the children, like Alana, born from cytoplasmic transfer is under scrutiny now because of the UK's decision to consider legalising mitochondrial replacement, where the mitochondria of a donor woman will be used to create a child.

It would not be available for people with fertility problems but for those who carry diseases of the mitochondria and would otherwise pass down these genetic abnormalities to their children.

Exactly how it is done still needs to be determined as there are two ways of doing the procedure, depending on when the eggs are fertilised.

Eggs from a mother with unhealthy mitochondria and a donor with healthy mitochondria are collected

The nucleus, containing the majority of the genetic material, is removed from both eggs. The donor nucleus is destroyed

The mother's nucleus is inserted into the donor egg - it now has healthy mitochondria. The egg is then fertilised by the father's sperm

Both the mother's and donor's eggs are fertilised with the father's sperm to create two embryos

The pronuclei, the nuclei during the process of fertilisation, contain the majority of the genetic material. They are removed from both embryos. The donor's is destroyed

A healthy embryo is created by putting the parents' pronuclei into the donor embryo

"Mitochondrial diseases tend to involve tissues or organs which are heavily dependent on energy," says Prof Doug Turnbull from The University of Newcastle. He has treated people with mitochondrial disease for decades and is one of those who has developed these new techniques to try to cure these debilitating diseases.

"The conditions can therefore involve the heart, the brain or sometimes the skeletal muscle," he says.

"People can have very bad heart problems which can cause the heart to fail eventually, they can be very weak and require respirators or be in a wheelchair. With the brain, they can get epilepsy, strokes and eventually severe dementia."

Turnbull estimates that around 1 in 3000-5000 people in the UK have a mitochondrial disease. "We can treat the symptoms. We can improve the quality and length of peoples' lives but we can't cure them."

The mitochondria carry some DNA, around 13 "important genes" says Turnbull.

That compares to the "23,000 important genes" in the nucleus where most of our DNA is held. This is the DNA that determines our traits and personality.

"We're not trying to create some characteristic that makes this person a stronger person or [someone who] will have blonde hair. We're trying to prevent disease and I think that is the only justification for doing this," he says.

Sharon Bernardi, from Sunderland in the North of England, is someone who mitochondrial replacement could have helped.

Bernardi has lost seven children to mitochondrial disease.

I have to slip back into reality and think don't be silly, Edward's not there. He's not in his room
Sharon Bernardi

"I have babies in three different cemeteries," she told us in her sitting room, surrounded by photographs of all her children.

"That is not the way you plan your life when you're trying to have a family. I have lovely photos and lovely memories but obviously that's all I have got now."

The doctors didn't know why Bernardi's babies kept passing away only hours after they were born. So that's why she kept trying, hoping she would have a healthy child.

With her fourth child, Edward, at first everything seemed different. He was healthy until he was about four and a half. But it was then that he was diagnosed with Leigh's disease, a type of mitochondrial disease, and his health deteriorated throughout the years.

"From the age of 20 Edward [found] getting around more difficult. He started to get new symptoms - spasms. He'd start screaming... four, five, six hours at a time. His muscles used to tense up, his hands, his face. It was like dystonic spasms - a really bad spasm. [For] eight hours he'd be in pain, screaming. His face would twist up and his hands would get really stiff. It was hard to see."

Edward Bernardi passed away three years ago, when he was 21.

"My life was totally for Edward. Even now sometimes if I have gone to sleep, I still wake up, and think, 'It's very quiet.' I have to slip back into reality and think, 'Don't be silly, Edward's not there. He's not in his room'."

"Without a heartbeat I would have gone for this [mitochondrial replacement]. I hope this is a new option. I hope people take it seriously and it's approved.

"I don't want my son to have just died for nothing. I want him to have made a difference."

"His life was robbed at 21. We're trying to stop this. People have to understand this is a life disease. We're trying not to pass it on to children and make it better for future families."

But some people believe this technique could set us on a slippery slope towards genetically modified humans.

"These regulations would authorise the crossing of a rubicon for the first time. It would authorise germ line therapy... to alter the genes of an individual. This is something defined by the EU Charter of Fundamental Rights as effectively constituting eugenics," says British MP Fiona Bruce who chairs the All Party Parliamentary Pro-Life Group.

There have been few episodes I'm aware of in the history of assisted reproduction that have had to be stopped because of hazard
Professor Braude, Kings College London

"We will have approved a technique and what that technique could be used for in the future who knows. We're opening a Pandora's box."

The regulator in the UK, the HFEA or Human Fertilisation and Embryology Authority, has held three independent reviews to scrutinise the safety of this technique. The conclusions were that mitochondrial replacement is "not unsafe".

That means "it would be reasonable, with some additional experiments, to take it into clinical practice if all circumstances are fulfilled" says Peter Braude, emeritus professor of obstetrics and gynaecology at Kings College London. He sat on all three HFEA scientific reviews.

"In any move from science to clinical practice there is a leap of faith - it has to be done," he says.

He adds that many of the concerns being raised now about this are the same as the ones cited in the early days of IVF. The UK has for decades been a leader in assisted reproduction science and is where the world's first test tube baby, Louise Brown, was born in 1978.

"The headlines then were 'playing God' and 'genetically modified humans'," says Braude.

"There have been few episodes I'm aware of in the history of assisted reproduction that have had to be stopped because of hazard. It's all gone pretty swimmingly as far as I'm aware."

Braude says that mitochondrial replacement has gone through much more scrutiny than previous, now well established, assisted reproduction techniques did, such as IVF.

"Whereas the original techniques were used with only [experiments from] mice, rabbits, lab animals... the big difference here is we also have issue of human embryos and this work has been tested in macaque monkeys in primates. All those were very useful, reassuring... hence why we came to the conclusion that this is not unsafe."

The experiments done on macaque monkeys were done in Oregon, US and the monkeys are now five years old and seem to be healthy.

Braude also points out that having a third person's DNA in your system is "nothing particularly new".

"Think about bone marrow transplants, let's say unfortunately you have leukaemia and you have to have your bone marrow radiated for the cancer to be killed and then it is replaced by bone marrow from someone else - say me. Effectively from that time onwards, you will have circulating in your body DNA from me. You won't be related to me, you may be grateful to me, but you will have DNA from a third person circulating in your body."

What is different, say critics, about mitochondrial replacement, is that DNA from the donor will be passed down future generations.

Dr Ted Morrow, an evolutionary biologist from the University of Sussex, and colleagues have carried out mitochondrial replacement experiments on other animals. He raised safety concerns about mitochondrial replacement to the scientific reviews.

"For mice, there were changes in cognitive ability... to learn and do things using their brain. In fruit flies and seed beetles there were changes in male fertility, changes in ageing, a range of different traits were effected in various experiments," he says.

I'm a scientist but I'm not a pro-lifer. I think this is a genuine safety concern - that's it
Ted Morrow, University of Sussex

The HFEA's scientific reviews dismissed Morrow's findings as not relevant to humans because they were done on inbred animals.

Morrow stands by his research and says the scientific panels should not have dismissed his findings so quickly.

It is Morrow's evidence that critics such as Fiona Bruce cite when saying this technique is not safe enough.

She has called a debate in the House of Commons today to discuss mitochondrial replacement. She does not believe there has been enough debate about what the UK is proposing to do. "The technique itself could allow the child to inherit untried untested medical complications," she says.

Morrow says that all the coverage of his research has been "a rather odd experience".

"In the press it's sometimes portrayed that the scientists think this, and the pro-life group this. I'm a scientist but I'm not a pro-lifer. I think this is a genuine safety concern - that's it."

Alana and Sharon Saarinen have been watching the debate in the UK with interest.

"I wish I could meet her, the donor, to tell her I am so grateful for what she did for us. How can you thank someone for giving you a life? That's impossible," says Sharon.
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Alana agrees with her mum. "I think it would be nice to thank her. But I wouldn't want to have a relationship or connection with her. The DNA I have of her is just so small."

"I know she might have another person's mitochondria, [but] look what a great person she turned out to be, and healthy. Just because she'll pass it on to her children it won't bother me in the least. I know it was the right thing to do. I have the living proof every day to see how great it turned out."

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Alana Saarinen loves playing golf and the piano, listening to music and hanging out with friends. In those respects, she's like many teenagers around the world. Except she's not, because every cell in Alana's body isn't like mine and yours - Alana is one of a few people in the world who have DNA from three people.

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More significantly for shoppers, the commission ruled out labelling food from the offspring of cloned animals claiming it would be unenforceable.

"This requires that parentage information for every food producing animal is conveyed through the food production chain," said the commission.

"This becomes more complicated and therefore costly with every generation between the clone and the animal, reproductive material and the food.

"For official controls, checking the accuracy of statements on labels would require in particular for food from offspring and descendant meticulous investigation into the accompanying documentation."

Because there are no restrictions on importing semen which has come from a cloned animal, it is likely that tens of thousands of pigs and cows in Europe are offspring of cloned stud animals from America.

In 2008, America's food safety authorities "concluded that meat and milk from cow, pig, and goat clones and the offspring of any animal clones are as safe as food we eat every day".

The EU imports 300,000 to 500,000 tons of beef every year, much of it comes from the US and Argentina, which authorise cloning for commercial purposes, usually for producing semen for artificial insemination leading to herds composed of the offspring of clones.

The proposals for an EU directive will "ban the use of the cloning technique for farm animals and the imports of these animal clones".

"The marketing of food from animal clones will also be prohibited," said the commission.

Animal welfare and consumer campaigners have expressed their disappointment with the failure to introduce an immediate ban.

"The proposals do not go far enough. As they do not ensure that a ban on the import and sale of animal clones, their offspring and food products from animal clones and their offspring as well as semen and embryos from animal clones is introduced immediately across the EU," said Reineke Hameleers, the director of Eurogroup for Animals.

"We urge the EU to stand firm and prevent the sale and import of food from cloned animals and their offspring, respecting the wishes of Europe's citizens by properly amending the proposed legislation quickly."

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Meat from cloned animals need not be labelled, EC says

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More significantly for shoppers, the commission ruled out labelling food from the offspring of cloned animals claiming it would be unenforceable. "This requires that parentage information for every food producing animal is conveyed through the food production chain," said the commission.

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You've probably seen pictures on the news of Lancelot Encore, an endearing Golden Lab puppy that was cloned using frozen DNA from his deceased predecessor, Sir Lancelot. Sir Lancelot's Florida family paid $150,000 to a South Korean pet-cloning company to re-create him in the form of a fluffy new puppy.

A Labrador puppy. Credit: Marco Togni

What is not reflected in the happy photos of the new puppy are the mistakes that might have come before him. Cloning mammals, especially dogs, is difficult. Scientists have to create and implant many embryos to birth a healthy one. (During the cloning process, DNA from the adult donor must be reprogrammed back to its embryonic state; that process can sometimes, perhaps most of the time, be incomplete.) RNL Bio, the commercial pet-cloning company, hasn't given a lot of details on the cloning process or posted figures on the number of embryos that it took to generate Lancelot Encore. But according to an article by the BBC, the success rate using the current method is in the single digits. In a recent experiment testing a new approach, two puppies were born from 84 embryos implanted into five surrogate mothers.

What of the other 90 percent? Some of those likely fail to implant, or spontaneously abort early on, but some may survive much longer and be stricken with serious or fatal health issues perinatally. I asked Robert Lanza, cloner extraordinaire and chief scientific officer at Advanced Cell Technology, about the downsides of cloning. (Lanza has cloned several endangered animal species, both successfully and unsuccessfully.)

Anyone who wants to have their pet cloned should ask themselves if they are willing to have one or two defective copies of "Fluffy" or "Spot" put down in order to get their pet back. Of course, cloning is associated with lots of abnormalities and genetic defects-and a significant percent of newborn animals die in the first few days or weeks of life.

Anyone who thinks they might be able to get Spot or Fluffy back is mistaken. Cloned animals have distinct personalities, just like identical twins. We cloned a herd of cattle several years ago-they were all cloned from a single individual. Yet they developed a social-dominance hierarchy just like a herd of ordinary dairy cows. The cloned animals exhibit the full spectrum of behavioral traits, from curious and inquisitive to timid and shy. There's no doubt about it: each cloned animal has its own unique, individual personality.

Note: The situation described above is distinct from human therapeutic cloning. The purpose of the former is to create an animal, while the purpose of the latter is to create stem cells for therapies or research. In human therapeutic cloning, which has yet to be accomplished, scientists would remove stem-cell precursors from the embryo early on, and embryos would never be implanted or allowed to develop past that early stage.

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You've probably seen pictures on the news of Lancelot Encore, an endearing Golden Lab puppy that was cloned using frozen DNA from his deceased predecessor, Sir Lancelot. Sir Lancelot's Florida family paid $150,000 to a South Korean pet-cloning company to re-create him in the form of a fluffy new puppy.