# data[].attributes.headline
Can become any blood cell - red, white, platelet

# data[].attributes.subject
Can become any blood cell - red, white, platelet

# data[].attributes.headline
Mammary stem cells are multipotent adult stem cells that reside in the mammary gland, can self-renew by dividing and can differentiate into all specialised mammary epithelial cells. Mammary stem cells drive the development of the mammary gland during puberty and are responsible for its expansion during pregnancy.

# data[].attributes.subject
Mammary stem cells are multipotent adult stem cells that reside in the mammary gland, can self-renew by dividing and can differentiate into all specialised mammary epithelial cells. Mammary stem cells drive the development of the mammary gland during puberty and are responsible for its expansion during pregnancy.

# data[].attributes.headline
Found in peripheral blood and the bone marrow

# data[].attributes.subject
Found in peripheral blood and the bone marrow

# data[].attributes.attachment_link.readable_text
Sense of smell restored

Dewald Kleynhans, University of Pretoria

Mice without a sense of smell have had the ability restored using stem cells delivered through the nose. The approach could pave the way for therapies that work in humans.

One in eight adults in the US has problems with olfaction as a consequence of ageing, infection, physical trauma or a genetic disorder. Most issues with smell are permanent, and there are few treatments, says Bradley Goldstein at the University of Miami.

While some studies have had success restoring smell in rodents using viral gene therapy, this is tailored for specific conditions. A stem cell-based approach could deal with a much broader set of olfactory problems.

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Goldstein says that many of the smell disorders that people develop through life appear to arise from problems in the tissue lining the nasal cavity, the olfactory epithelium.

"It seems like some failures might be in repairing damage," Goldstein says. "So we were really interested to know if there was a way to replace or restore those damaged cells that could be beneficial."

First, they genetically modified mice so that the neurons in their noses that are needed to sense smells - olfactory sensory neurons - didn't have any of the hair-like structures that normally pick up odours.

Then Goldstein and his team squirted droplets of so-called basal cells, which are responsible for the replacement of these neurons when they are old or damaged, into the rodents' noses.

These stem cells successfully created mature, working olfactory sensory neurons in the nasal cavity, which then connected to the olfactory bulb in the brain.

When they tested the mice, they found those that were genetically modified with the faulty smelling neurons showed an inability to detect a bad smell. However, those with the genetic modification that had then had the stem cell treatment reacted to the smell in the way a regular mouse would.

As well as the simple joy that comes from smelling a rose or the flood of memories sparked by sniffing a lover's jumper, our sense of smell is a vital and effective warning system. Smoke, chemicals and spoiled food are all dangers that we can avoid with a healthy sense of smell, Goldstein says.

While Goldstein and his team found no evidence that mice developed tumours from the therapy, he notes that there are many more safety and efficacy hurdles to pass before the technique could be tested in humans.

"The olfactory nerves are kind of the highway that connect up through the roof of the nose intracranially to connect to the brain, so we certainly want to make sure that there's no unintended delivery of cells to other places where we didn't want them to go," Goldstein says.

Journal reference: Stem Cell Reports, DOI: 10.1016/j.stemcr.2019.05.001

# data[].attributes.attachment_link.title
Damaged sense of smell fixed in mice by squirting stem cells up nose

# data[].attributes.attachment_link.description
Mice without a sense of smell have had the ability restored using stem cells delivered through the nose. The approach could pave the way for therapies that work in humans. One in eight adults in the US has problems with olfaction as a consequence of ageing, infection, physical trauma or a genetic disorder.

# data[].attributes.body
Intestinal stem cells are multipotent adult stem cells, which in mammals reside in the base of the crypts of the adult intestine. Intestinal stem cells continuously self-renew by dividing and differentiate into the specialised cells of the intestinal epithelium, which renews throughout life.

# data[].attributes.body
Are multipotent adult stem cells

# data[].attributes.body
https://pituitary.org/item/olfactory-cells

# data[].attributes.body
The intestinal epithelium is a single layer of cells organized into crypts and villi, known as the most rapidly self-renewing tissue in adult mammals. The cells that line the intestinal lumen perform the primary functions of digestion, water and nutrient absorption, and forms a barrier against luminal pathogens.

# data[].attributes.body
https://ars.els-cdn.com/content/image/3-s2.0-B9780323396325000232-f23-05-9780323396325.jpg

# data[].attributes.headline
Olfactory receptors (ORs), also known as odorant receptors, are expressed in the cell membranes of olfactory receptor neurons and are responsible for the detection of odorants (i.e., compounds that have an odor) which give rise to the sense of smell.

# data[].attributes.subject
Olfactory receptors (ORs), also known as odorant receptors, are expressed in the cell membranes of olfactory receptor neurons and are responsible for the detection of odorants (i.e., compounds that have an odor) which give rise to the sense of smell.

# data[].attributes.headline
The term 'mammary' relates to the breasts, specifically the milk glands in the breasts

# data[].attributes.subject
The term 'mammary' relates to the breasts, specifically the milk glands in the breasts

# data[].attributes.headline
Mammary stem cells are found in the mammary gland in the breast

# data[].attributes.subject
Mammary stem cells are found in the mammary gland in the breast

# data[].attributes.headline
The stem cells that form blood and immune cells are known as hematopoietic stem cells (HSCs). They are ultimately responsible for the constant renewal of blood—the production of billions of new blood cells each day.

# data[].attributes.subject
The stem cells that form blood and immune cells are known as hematopoietic stem cells (HSCs). They are ultimately responsible for the constant renewal of blood—the production of billions of new blood cells each day.

# data[].attributes.body
As with most glandular tissues, the adult mammary gland is composed of multiple cell types, including epithelial, adipose, fibroblasts, immune, lymphatic and vascular cells, that work together to sculpt and maintain a functional organ. These different cell types have been demonstrated to be of importance at specific stages of mammary gland development.

# data[].attributes.attachment_link.readable_text
I've often said in my writings that I have yet to encounter a for-profit stem cell clinic that is not a predatory quack clinic selling unproven treatments for serious diseases at high prices. Although I've been writing about this phenomenon and how these clinics continue to operate for quite a long time now, my interest was particularly piqued when a hometown hero, Gordie Howe, went to Mexico for an infusion of stem cells to treat his serious stroke. As a result, even though he was hardly ever shown, he became a de facto celebrity pitch man for Stemedica Cell Technologies, the San Diego company that made the stem cell product that he received at the Mexican clinic and had provided it to Howe at no cost other than his travel. Never mind that there was no good evidence that the stem cell infusion improved Howe's neurologic function. More recently, William Shatner touted an "anti-aging" stem cell infusion that he had undergone. Meanwhile, there have been reports of spinal cord tumors as a result of dubious stem cell treatments. As the FDA tries to crack down on the most egregious offenders selling stem cell quackery, there comes another reminder that, contrary to what stem cell entrepreneurs tell us, these treatments are not without risk-in some cases, significant risk, in the form of a case report from Newfoundland in Canada of a man with a cervical spine mass after a stem cell treatment. The mass turned out to be an olfactory mucosa stem cell tumor.

Here's the case history:

A 38-year-old man was referred to the neurosurgical clinic with a 3- to 4-year history of deteriorating neurologic function in his arms (sensory disturbance with some subjective weakness) and gradual loss of bladder function. The patient's medical history included a C5/C6 fracture-dislocation secondary to trauma at 20 years of age. Despite having had posterior spinal fusion and rehabilitation, he had partial paralysis of his arms, and severe paralysis of his legs and trunk. According to the American Spinal Injury Association (ASIA) Impairment Scale (AIS) (https://asia-spinalinjury.org/wp-content/uploads/2019/04/ASIA-ISCOS-IntlWorksheet_2019.pdf), which grades impairment after spinal cord injury from A (complete motor and sensory deficits) to E (neurologically intact), he had sustained an ASIA D injury (i.e., motor incomplete). This means that half or more of the key muscles below the neurologic level of injury were active against gravitational resistance. At 26 years of age, the patient had undergone experimental stem cell transplantation. Using a nasal approach, the surgical team harvested an olfactory mucosa graft that was transplanted to his spinal cord lesion on the next day. Although the patient could not provide an operative report, the surgical team (Lima and colleagues) published their transplantation and surgical procedure.1 Fusion hardware was removed and he again underwent rehabilitation. Although he hoped to walk again and have resolution of his chronic pain, he never regained clinically significant motor function, and he experienced additional pain.

This is, of course, a horrific injury. This man had very severe neurologic deficits and was, in essence, a quadriplegic. Now, here's the interesting thing. This procedure appears not to have been performed at a for-profit quack stem cell clinic. Rather, it was performed in Portugal at Hospital de Egas Moniz in Lisbon and the clinical trial protocol approved by the hospital's ethics committee and published by Carlos Lima

I was intrigued by the procedure; so I looked up the clinical trial protocol. The timeline fits, because the operations for the clinical trial were carried out between 2001 and 2003. The trial itself enrolled seven patients ranging from 18 to 32 years of age with spinal cord injury (four men and three women). All had suffered serious spinal cord injury with paralysis, and all injuries had resulted from motor vehicle collisions save one, which had resulted from a fall.

The authors described the rationale for using olfactory mucosa grafts:

There are several potential advantages of olfactory mucosa transplants. The olfactory mucosa is a structural unit with embryonic features that offer the possibility of promoting regeneration and reconstruction. Removing part of the olfactory mucosa does not permanently damage olfaction because it is a continuously regenerating system. By using the olfactory mucosa to fill the spinal cord cavity with solid tissue as opposed to using cell suspensions, there is decreased risk of individual cells entering the cerebrospinal fluid (CSF) circulation. In an experimental transplant study, tissue (as opposed to cell suspensions derived from that tissue) was more effective and showed greater cell viability (12). During the period of adaptation to the new environment, cells may be supported by their original surrounding cell types. Olfactory mucosa transplants avoid the artificial environment of tissue culture, which also reduces the risks of the procedure. Instead, olfactory mucosa grafts preserve the CSF environment, because CSF also bathes the olfactory mucosa through the olfactory route of CSF drainage (13). The autologous olfactory mucosa graft would not be an additional burden to the immune system, because the grafted material was previously exposed to the contemporary immunological state of the central nervous system.

In addition, it is known that the two cell types in the olfactory mucosa known to be useful in the repair of the nervous system are stem-like progenitor cells and olfactory ensheathing cells (OECs). The stem-like progenitor cells divide rapidly and can develop into neurons or supporting cells. There are also a number of promising animal studies that suggest that these cells can contribute to the repair of damaged neurons. As a result, it was thought that there was sufficient preclinical evidence to do a pilot study.

The surgical procedure itself involved multiple teams and three steps. The first step involved neurosurgeons exposing the damaged spinal cord and removing as much scar tissue as possible to expose the gross viable nervous tissue in both stumps of the severed cord. This wound was temporarily closed, and then the otolaryngologists went into action to harvest the olfactory mucosa graft. Finally, the graft was implanted into the site of injury. The graft was immersed in saline or cerebrospinal fluid and cut into small pieces, after which the graft was placed at the site of injury. Patients were transferred to the surgical intensive care unit.

Six months after transplantation, MRI showed filling of the defect in the spinal cord in all patients but one, with no evidence of tumor overgrowth. There was some improvement in every patient, but reading the report, I couldn't see the results as anything more than mildly promising and worth following up, which the same team of investigators did in a prospective, uncontrolled pilot study of olfactory mucosal autograft implantation in 20 patients who had sustained traumatic spinal cord injury 18 to 189 months previously (mean 49 months). The AIS scores improved in 11 of 20 patients and declined only in 1 patient.

However, as promising as these results might sound, we must be cautious, as the authors of the case report of the spinal mass suggest:

Studies involving transplantation using olfactory mucosal autografts notably carry several limitations. To date, patient enrollment is small, making the generalizability of results difficult. The studies are neither randomized nor blinded. The relative contributions of intensive postoperative rehabilitation and olfactory mucosa transplantation to recovery are unclear given the lack of large control groups. Some studies with questionable rehabilitation intensity and compliance showed no postoperative improvement in ASIA motor score. Although these studies claim that olfactory mucosal autograft transplantation is feasible and safe given the few adverse events encountered, their follow-up periods are limited.

Now, at a followup of around 17 years, this patient presented with a cervical spine mass, as seen on this MRI:

The mass is best seen in A as an irregular area against the vertebral bones. Don't worry if you can't read the MRI; I included it for those who can. The mass extends from the C4 to C7 vertebrae. You don't need to be able to read MRIs to see the the mass in this surgical photo from the exploration and resection of the mass:

The suction catheter shows very thin mucinous material that was expressed from the mass (white arrow). Solid components were adherent to and infiltrating the spinal cord, resulting in the surgeons not being able resect the entire mass. So they did a subtotal resection. This is what pathology found:

Pathologic examination of the samples found mucinous material and tissue consistent with ectopic olfactory mucosa. The sections showed tissue and small cysts lined by a pseudostratified columnar epithelium (Figure 3A). Nerve twigs and submucosa glands were seen in the underlying connective tissue, with 1 slide showing bone. Results from examination of tissue using immunohistochemistry showed neurofilaments and S100 proteins within the nerve twigs, and perineurial cells that were positive for epithelial membrane antigen and glial fibrillary acidic protein positivity in some areas, likely representing gliotic spinal tissue (Figure 3B).

Translation: This was a mass with mucus in it and tissue consistent with olfactory mucosa and thus deriving from the olfactory mucosa graft. The prognosis after surgery is basically unknown. The authors report:

Between discharge and follow-up at 6 weeks, the patient became severely deconditioned because of admissions to hospital for urinary tract infection and acute pancreatitis. His injury remained classified as ASIA D, but a physical examination found either stability or slight loss of power in the myotomes of his arms and legs. Given the subtotal resection of the mass, radiotherapy was offered after consultation with colleagues in other centres in Canada to try to sterilize any residual cells in the hope of slowing regrowth of the mass. The benefit of radiation in this setting is unknown; however, further surgical resection was not possible, and there was no role for chemotherapy. Treatment with radiotherapy and rehabilitation and surveillance are ongoing.

In other words, if the radiation doesn't work and the mass recurs, options will be very limited. Nor is this the only case of a mass following an olfactory bulb mucosa graft for spinal cord injury. The authors review several other cases of mass lesions following olfactory mucosal autografting in the medical literature, one who underwent surgery by the same medical team as the patient in this case report. Two other cases involving patients who developed similar spinal masses 5 and 7 years after autologous olfactory mucosa transplantation have been reported.

One thing that should be noted is that these patients underwent stem cell grafting procedures at a public hospital under an ethics panel-approved clinical trial protocol, and they suffered serious complications in the form of masses growing where their grafts were implanted and causing more damage to the spinal cord. Given the gap of many years between surgery and growth of the mass to the point where it caused symptoms, it's quite possible that additional masses will be detected. Even so, I saw an additional red flag that might not have been picked up on in reports of these cases. The man in the case report I discussed is a Canadian citizen, and the woman who also developed a mass after this procedure is an American:

At a hospital in Portugal, the unnamed woman, a US citizen, had tissue containing olfactory stem cells taken from her nose and implanted in her spine. The hope was that these cells would develop into neural cells and help repair the nerve damage to the woman's spine. The treatment did not work - far from it. Last year the woman, then 28, underwent surgery because of worsening pain at the implant site. The surgeons removed a 3-centimetre-long growth, which was found to be mainly nasal tissue, as well as bits of bone and tiny nerve branches that had not connected with the spinal nerves. The growth wasn't cancerous, but it was secreting a "thick copious mucus-like material", which is probably why it was pressing painfully on her spine, says Brian Dlouhy at the University of Iowa Hospitals and Clinics in Iowa City, the neurosurgeon who removed the growth. The results of the surgery have now been published.

OK, so reputable public hospital or not, this is stem cell tourism. Now, putting it together, there are two additional observations that got my skeptical antennae twitching. Her's the first one, from the Canadian case report:

Olfactory mucosal autograft surgery costs about $50 000; with patients facing additional expenses for travel, accommodations, caregiver support and recuperation, this price can easily double. The subsequent cost for managing any complications in Canada can be the same because these patients require ongoing multidisciplinary care.

This got me thinking: Did the patients pay for the surgery? It seems rather likely that the foreign participants in this clinical trial, at the very least, paid for their surgery. Hmmm.

Now here's the second observation, from a New Scientist story about the woman who developed a mass on her spine after this procedure:

was unable to reach the Lisbon team members, but Jean Peduzzi-Nelson, a stem cell researcher at Wayne State University in Detroit, Michigan, who advised the team on their surgical technique - she had previously tested it on rodents - claims the clinic has given the therapy to about 140 people in total. Peduzzi-Nelson adds that most of the recipients of the nasal tissue who received the right kind of rehabilitation after their surgery experienced improvement. "I am saddened to learn of this adverse event, however, the incidence of this problem is less than 1 per cent," she says. "Many patients receiving this treatment have had remarkable recovery."
New Scientist

My first reaction was: "Less than one percent"? That's quite a lot, actually, given the potential morbidity and even mortality when this complication occurs. Partial paralysis could easily become complete paralysis, and pain can become unbearable.

They have? Or should I say: They had? After all, the above article is five years old. Funny, but the Canadian researchers who just published the case report I discussed did a literature review, and they didn't mention any later studies encompassing hundreds of patients. So I hit PubMed. Nope, nothing more to see there. The last clinical trial by Carlos Lima involving olfactory mucosal autografts dates back to 2010 and was the pilot trial of 20 patients. Peduzzi-Nelson appears to have suggested that Lima's group has done way more than 20 olfactory mucosa autografts than just 27 (the seven from the first pilot study and the 20 from the second). Which is true? Has Lima only done 27 under his clinical trial protocols, or has he gone beyond that and continued to treat patients? Does he charge for the procedure? You see where I'm going with this? Is he becoming, for all intents and purposes, no different than the for-profit stem cell clinics I regularly castigate for their unethical practices? If he is continuing to do the procedure, why hasn't he published further about it in nine years? Is the hospital charging patients the $50,000 or more for the procedure, even though it is, by any stretch of the imagination,

I definitely smell something fishy here.

Leaving that aside, though, the most important thing to remember from this case report, the author's conclusion:

Given the vulnerability of patients who are chronically ill, especially those with spinal cord injury or neurologic disorders who may be targets of Internet-based marketing for stem cell therapy), physicians in Canada should be aware of the rationale behind stem cell therapy as well as the reported adverse events. Both family physicians and specialists may need to counsel patients on stem cell transplantation or diagnose complications in those who have had these procedures.

Precisely. Even under the auspices of a properly designed clinical trial approved by an institutional review board, there is the potential for serious adverse reactions from stem cells. Now just imagine what could happen as a result of the unregulated sale of unproven stem cell therapies.

ADDENDUM: I just discovered that Carlos Lima died in 2012, although apparently his work still goes on. His group also claimed to have done over 120 of these procedures.

# data[].attributes.attachment_link.title
Olfactory mucosa tumors: Another complication of stem cell treatments - RESPECTFUL INSOLENCE

# data[].attributes.attachment_link.description
I've often said in my writings that I have yet to encounter a for-profit stem cell clinic that is not a predatory quack clinic selling unproven treatments for serious diseases at high prices.

# data[].attributes.headline
Intestinal epithelial cells (IECs) line the surface of intestinal epithelium, where they play important roles in the digestion of food, absorption of nutrients, and protection of the human body from microbial infections, and others.

# data[].attributes.subject
Intestinal epithelial cells (IECs) line the surface of intestinal epithelium, where they play important roles in the digestion of food, absorption of nutrients, and protection of the human body from microbial infections, and others.

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Haematopoeitic
Can become any blood cell - red, white, platelet
Can become any blood cell - red, white, platelet
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Found in peripheral blood and the bone marrow
Found in peripheral blood and the bone marrow
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Also found in umbilical cord blood
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The stem cells that form blood and immune cells are known as hematopoietic stem cells (HSCs). They are ultimately responsible for the constant renewal of blood—the production of billions of new blood cells each day.
The stem cells that form blood and immune cells are known as hematopoietic stem cells (HSCs). They are ultimately responsible for the constant renewal of blood—the production of billions of new blood cells each day.
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cells are multipotent
cells are multipotent
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Mammary stem cells are multipotent adult stem cells that reside in the mammary gland, can self-renew by dividing and can differentiate into all specialised mammary epithelial cells. Mammary stem cells drive the development of the mammary gland during puberty and are responsible for its expansion during pregnancy.
Mammary stem cells are multipotent adult stem cells that reside in the mammary gland, can self-renew by dividing and can differentiate into all specialised mammary epithelial cells. Mammary stem cells drive the development of the mammary gland during puberty and are responsible for its expansion during pregnancy.
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https://www.nature.com/subjects/mammary-stem-cells
https://www.nature.com/subjects/mammary-stem-cells
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The term 'mammary' relates to the breasts, specifically the milk glands in the breasts
The term 'mammary' relates to the breasts, specifically the milk glands in the breasts
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Mammary stem cells are found in the mammary gland in the breast
Mammary stem cells are found in the mammary gland in the breast
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https://www.verywellhealth.com/epithelial-cells-definition-430052
https://www.verywellhealth.com/epithelial-cells-definition-430052
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As with most glandul
As with most glandular tissues, the adult mammary gland is composed of multiple cell types, including epithelial, adipose, fibroblasts, immune, lymphatic and vascular cells, that work together to sculpt and maintain a functional organ. These different cell types have been demonstrated to be of importance at specific stages of mammary gland development.
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Intestinal stem cells are multipotent adult stem cells, which in mammals reside in the base of the crypts of the adult intestine. Intestinal stem cells continuously self-renew by dividing and differentiate into the specialised cells of the intestinal epithelium, which renews throughout life.
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Intestinal stem cells continuously self-renew by dividing and differentiate into the specialised cells of the intestinal epithelium, which renews throughout life.
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Are multipotent adult stem cells
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The intestinal epithelium is a single layer of cells organized into crypts and villi, known as the most rapidly self-renewing tissue in adult mammals. The cells that line the intestinal lumen perform the primary functions of digestion, water and nutrient absorption, and forms a barrier against luminal pathogens.
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Intestinal epithelial cells (IECs) line the surface of intestinal epithelium, where they play important roles in the digestion of food, absorption of nutrients, and protection of the human body from microbial infections, and others.
Intestinal epithelial cells (IECs) line the surface of intestinal epithelium, where they play important roles in the digestion of food, absorption of nutrients, and protection of the human body from microbial infections, and others.
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📎 Damaged sense of smell fixed in mice by squirting stem cells up nose
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Olfactory receptors (ORs), also known as odorant receptors, are expressed in the cell membranes of olfactory receptor neurons and are responsible for the detection of odorants (i.e., compounds that have an odor) which give rise to the sense of smell.
Olfactory receptors (ORs), also known as odorant receptors, are expressed in the cell membranes of olfactory receptor neurons and are responsible for the detection of odorants (i.e., compounds that have an odor) which give rise to the sense of smell.
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A review of more than 200 studies reveals that olfactory receptors -- proteins that bind to odors that aid the sense of smell -- perform a wide range of mostly unknown functions outside the nose. The function of extra-nasal olfactory receptors has the potential to be used in the diagnosis and treatment of health conditions such as cancer. The article is published in the July issue of Physiological Reviews.

Olfactory, or smell, receptors were originally thought to be only in the sensory nerve cells (neurons) of nasal cavity tissues. However, more recent and extensive study suggests that the receptors "occur in nearly the entire human body, [and] they appear to be substantially more functionally important than previously suggested," researchers from Ruhr-University Bochum in Germany wrote. In addition to the receptors playing a major role in the sense of smell, "several essential physiological and pathophysiological processes have been described as targeted by human [olfactory receptors], including path finding, cell growth, [cell death], migration and secretion."

The research team summarized the location and purpose of certain types of olfactory receptors, including those that may be beneficial to general health:

Receptors present in heart muscle cells may be a metabolic regulator of heart function.

Receptors activated in the immune system have been seen to promote the death of certain types of leukemia cells.

Smell receptors in the liver reduce the spread of liver cancer cells.

Receptors in the skin increase the regeneration of skin cells and help speed wound healing.

The review also reveals ways in which olfactory receptors may affect the development of disease, including:

Receptors concentrated in the prostate tissue, especially in men with prostate cancer, contribute to the reduction or progression of the disease.

Receptors in the colon may reduce the growth of colon cancer cells.

Receptors in the digestive tract may cause chronic diarrhea or constipation but may also contribute to better digestion.

The existence of olfactory receptors outside the nose -- either positive or negative -- plays an important role in disease progression and physiological function but is not yet fully understood. Their role as a possible biomarker for disease requires more research, the authors said. Study "must be expanded to develop promising clinical strategies in the future," the researchers wrote.

# data[].attributes.attachment_link.keywords[]
diseases and conditions; prostate cancer; lymphoma; colon cancer; chronic illness; stem cells; nervous system; skin cancer

# data[].attributes.attachment_link.title
Smell receptors in the body could help sniff out disease: Olfactory cells found throughout the body may help or harm depending on location

# data[].attributes.attachment_link.description
A review of more than 200 studies reveals that olfactory receptors -- proteins that bind to odors that aid the sense of smell -- perform a wide range of mostly unknown functions outside the nose. The function of extra-nasal olfactory receptors has the potential to be used in the diagnosis and treatment of health conditions such as cancer.

# data[].attributes.body
https://breast-cancer-research.biomedcentral.com/articles/10.1186/bcr1021

# data[].attributes.body
http://www.bloodjournal.org/content/131/5/479

# data[].attributes.attachment_link.readable_text
A team of researchers at Tufts University School of Medicine developed a method to grow and maintain olfactory stem cells in culture, which can then be used to restore tissue in the nose. The discovery raises hope that future therapies could be developed to restore the sense of smell in individuals where it has been damaged by injury or degeneration.

The stem cells, called horizontal basal cells (HBCs), can repopulate all olfactory epithelium (OE) cell types, including sensory neurons, when transplanted into injured tissue. Published today in the journal Stem Cell Reports, the development paves the way for further research into stem cell transplantation therapies, or pharmacological approaches that stimulate stem cells within the nose to regenerate tissue.

The nerves that confer the sense of smell are unique when compared to the rest of the nervous system, in that they can trigger a robust and nearly complete regenerative response after injury. OE tissue contains two types of stem cells -- globose basal cells (GBCs) and HBCs. The GBCs have been successfully cultured and appear to have a primary role in repopulating cells that have been lost to routine turnover. HBCs, however, remain dormant and are not activated until there is an injury. Unfortunately, studies on these cells have been limited by the fact that they could not be expanded and maintained in culture. In this study, the researchers determined the optimal conditions for expanding and maintaining healthy HBC stem cells in culture, borrowing methods and factors used to maintain respiratory stem cells.

"Once we determined that we could grow HBCs in the lab, and that they expressed the same identifying molecular markers found in vivo, we sought to confirm whether they would work as well as the in vivo HBCs -- can they regenerate tissue that has been injured -- and they did!" said James Schwob, M.D., Ph.D., professor of developmental molecular and chemical biology at Tufts University School of Medicine, and corresponding author for the study.

Despite a natural ability for regeneration, dysfunction in the sense of smell is still reported among 19.4 percent of the population (OLFACAT study, 2003), with 0.3 percent experiencing complete loss of smell. Causes range from aging, injury, smoking, and neurodegenerative diseases to certain medications.

Schwob and his team discovered that the lab-grown HBCs were able to fill in olfactory lesions, generating multiple cell types including Sus cells, basal cells and olfactory sensory neurons.

"The HBCs in culture remained quiescent, pretty much as they do in vivo, but we were able to trigger them into an active state to start the process of differentiation into various olfactory epithelial cells just before engrafting them into injured tissue," said Jesse Peterson, Ph.D., first author of the study and currently a post-doctoral fellow at the MRC Laboratory of Molecular Biology. Peterson conducted the study as part of his doctoral dissertation at the Sackler School of Graduate Biomedical Sciences at Tufts, advised by Schwob.

The trigger used was retinoic acid, which has the effect of lowering levels of the protein P63 in the cells, leading to stem cell activation. P63 functions as a "master control switch" and is known to decrease levels during injury, transitioning HBCs from dormancy to activation in vivo. A more thorough understanding of the role of P63 has been hampered by the slow pace of in vivo studies. With lab-grown HBCs, the mechanisms of activation can be examined more closely.

"Now that we can create a reserve of dormant stem cells, we see this as a useful tool for exploring ways to guide cell differentiation toward specific cell types, and develop new stem cell therapies for tissue and sensory regeneration -- using the patient's own stem cells for culturing and transplantation, or pharmacological interventions to activate the patient's own dormant stem cells within the nose," said Schwob.

Other authors contributing to this study are Brian Lin, Ph.D., Camila Barrios-Camacho, Daniel Herrick, M.D., Ph.D., and Julie Coleman, Ph.D., all graduates or students at Tufts, Woochan Jang, Ph.D., former research assistant professor at Tufts, and Eric Holbrook, M.D., of Massachusetts Eye and Ear, and Harvard Medical School.

This work was supported by awards from the National Institutes of Health's National Institute on Deafness and Other Communication Disorders (R01DC002167, F31DC014637, F30DC013962, F31DC014398). This content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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stem cells; prostate cancer; skin cancer; nervous system; brain injury; neuroscience; k-12 education; perception

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Cultured stem cells reconstruct sensory nerve and tissue structure in the nose: Lab-grown olfactory stem cells will enable research into therapies for recovering sense of smell after injury or degeneration

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Researchers have developed a method to grow and maintain olfactory stem cells. The work is a launch pad for developing stem cell transplantation therapies or pharmacologic activation of a patient's own dormant cells, to restore the sense of smell where it has been damaged by injury or degeneration.

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https://youtu.be/pl1sb_S78LA

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The olfactory epithelium (OE) of vertebrates is a highly regenerative neuroepithelium that is maintained under normal conditions by a population of stem and progenitor cells, globose basal cells (GBCs), which also contribute to epithelial reconstitution after injury. However, aging of the OE often leads to neurogenic exhaustion, the disappearance of both GBCs and olfactory sensory neurons (OSNs). Aneuronal tissue may remain as olfactory, with an uninterrupted sheet of apically arrayed microvillar-capped sustentacular cell, or may undergo respiratory metaplasia. We have generated a transgenic mouse model for neurogenic exhaustion using olfactory marker protein-driven Tet-off regulation of the A subunit of Diphtheria toxin such that the death of mature OSNs is accelerated. At as early as 2 months of age, the epithelium of transgenic mice, regardless of sex, recapitulates what is seen in the aged OE of humans and rodents. Areas of the epithelium completely lack neurons and GBCs; whereas the horizontal basal cells, a reserve stem cell population, show no evidence of activation. Surprisingly, other areas that were olfactory undergo respiratory metaplasia. The impact of accelerated neuronal death and reduced innervation on the olfactory bulb (OB) was also examined. Constant neuronal turnover leaves glomeruli shrunken and affects the dopaminergic interneurons in the periglomerular layer. Moreover, the acceleration of OSN death can be reversed in those areas where some GBCs persist. However, the projection onto the OB recovers incompletely and the reinnervated glomeruli are markedly altered. Therefore, the capacity for OE regeneration is tempered when GBCs disappear.SIGNIFICANCE STATEMENT A large percentage of humans lose or suffer a significant decline in olfactory function as they age. Therefore, quality of life suffers and safety and nutritional status are put at risk. With age, the OE apparently becomes incapable of fully maintaining the neuronal population of the epithelium despite its well known capacity for recovering from most forms of injury when younger. Efforts to identify the mechanism by which olfactory neurogenesis becomes exhausted with age require a powerful model for accelerating age-related tissue pathology. The current OMP-tTA;TetO-DTA transgenic mouse model, in which olfactory neurons die when they reach maturity and accelerated death can be aborted to assess the capacity for structural recovery, satisfies that need.

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http://cdn.sci-news.com/images/enlarge4/image_5981e-Stem-Cell-Regeneration.jpg

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https://jcs.biologists.org/content/118/16/3585

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There are two types of hematopoietic cell transplantation, autologous and allogeneic. An autologous hematopoietic cell transplant uses a patient's own bone marrow or blood.

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https://swissmedica.startstemcells.com/lp4/?utm_source=GoogleAdsEN&utm_medium=Search_Stemcells_Artilleria&utm_campaign=stem-cells&utm_content=168744658041&utm_term=%2Bstem%20%2Bcell

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Intestinal epithelial cells (IECs) line the surface of intestinal epithelium, where they play important roles in the digestion of food, absorption of nutrients, and protection of the human body from microbial infections, and others.

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https://www.embopress.org/doi/10.15252/embj.201798791

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Cognitive problems are a significant, persistent concern for patients undergoing hematopoietic stem cell

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April 27, 2018

Mayo Clinic is enrolling patients in a phase 1 clinical trial of adipose stem cell treatment for spinal cord injury caused by trauma. The researchers already have approval from the Food and Drug Administration for subsequent phase 2A and 2B randomized control crossover trials.

Participants in the phase 1 clinical trial must have experienced a trauma-related spinal cord injury from two weeks to one year prior to enrollment. They will receive intrathecal injections of adipose-derived mesenchymal stem cells. No surgery or implantable medical device is required.

"That is the most encouraging part of this study," says Mohamad Bydon, M.D., a consultant in Neurosurgery specializing in spinal surgery at Mayo Clinic in Rochester, Minnesota, and the study's director. "Intrathecal injection is a well-tolerated and common procedure. Stem cells can be delivered with an implantable device, but that would require surgery for implantation and additional surgeries to maintain the device. If intrathecal treatment is successful, it could impact patients' lives without having them undergo additional surgery or maintain permanently implantable devices for the rest of their lives."

To qualify for the trial, patients must have a spinal cord injury of grade A or B on the American Spinal Injury Association (ASIA) Impairment Scale. After evaluation at Mayo Clinic, eligible patients who enroll will have adipose tissue extracted from their abdomens or thighs. The tissue will be processed in the Human Cellular Therapies Laboratories, which are co-directed by Allan B. Dietz, Ph.D., to isolate and expand stem cells.

Four to six weeks after the tissue extraction, patients will return to Mayo Clinic for intrathecal injection of the stem cells. The trial participants will then be evaluated periodically for 96 weeks.

Mayo Clinic has already demonstrated the safety of intrathecal autologous adipose-derived stem cells for neurodegenerative disease. In a previous phase 1 clinical trial, with results published in the Nov. 22, 2016, issue of Neurology, Mayo Clinic researchers found that therapy was safe for people with amyotrophic lateral sclerosis (ALS). The therapy, developed in the Regenerative Neurobiology Laboratory under the direction of Anthony J. Windebank, M.D., is moving into phase 2 clinical trials.

Dr. Windebank is also involved in the new clinical trial for people with traumatic spinal cord injuries. "We have demonstrated that stem cell therapy is safe in people with ALS. That allows us to study this novel therapy in a different population of patients," he says. "Spinal cord injury is devastating, and it generally affects people in their 20s or 30s. We hope eventually that this novel therapy will reduce inflammation and also promote some regeneration of nerve fibers in the spinal cord to improve function."

Mayo Clinic's extensive experience with stem cell research provides important guidance for the new trial. "We know from prior studies that stem cell treatment can be effective in aiding with regeneration after spinal cord injury, but many questions remain unanswered," Dr. Bydon says. "Timing of treatment, frequency of treatment, mode of delivery, and number and type of stem cells are all open questions. Our hope is that this study can help answer some of these questions."

In addition to experience, Mayo Clinic brings to this clinical trial the strength of its multidisciplinary focus. The principal investigator, Wenchun Qu, M.D., M.S., Ph.D., is a consultant in Physical Medicine and Rehabilitation at Mayo Clinic's Minnesota campus, as is another of the trial's investigators, Ronald K. Reeves, M.D. Dr. Dietz, the study's sponsor, is a transfusion medicine specialist. Also involved is Nicolas N. Madigan, M.B., B.Ch., BAO, Ph.D., a consultant in Neurology at Mayo Clinic's Minnesota campus.

The study team is in discussions with U.S. military medical centers to enroll patients, and discussing additional collaboration with international sites, potentially in Israel or Europe, for future phases of the study.

"At Mayo Clinic, we have a high-volume, patient-centered multidisciplinary practice," Dr. Bydon says. "That allows us to do the most rigorous scientific trial that is in the best interests of our patients."

For more information

Mayo Clinic. Adipose Stem Cells for Traumatic Spinal Cord Injury (CELLTOP). ClinicalTrials.gov.

Staff NP, et al. Safety of intrathecal autologous adipose-derived mesenchymal stromal cells in patients with ALS. Neurology. 2016;87:2230.

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Clinical trial of stem cell therapy for traumatic spinal cord injury

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April 27, 2018 Mayo Clinic is enrolling patients in a phase 1 clinical trial of adipose stem cell treatment for spinal cord injury caused by trauma. The researchers already have approval from the Food and Drug Administration for subsequent phase 2A and 2B randomized control crossover trials.

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Thomas' research strongly supported the existence of hematopoietic stem cells as well. Thomas and his team discovered through work in dogs that there were specific cells in bone marrow that could restore hematopoiesis after lethal irradiation.

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Hematopoietic stem cell transplants are now routinely used to treat patients with cancers and other disorders of the blood and immune systems. Recently, researchers have observed in animal studies that hematopoietic stem cells appear to be able to form other kinds of cells, such as muscle, blood vessels, and bone.

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Scroll down the website for stem cells specifically

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Scroll down the website for stem cells specifically

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http://genesdev.cshlp.org/content/22/14/1856.full

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Many animals taste and smell their environment through the same part of their body, but can the same be true about humans? New research suggests that this might indeed be the case and that we may have smell receptors on our tongues.

A new study suggests that the human tongue may be able to do much more than taste.
Unlike humans and other mammals, not all animals have noses with smell receptors, but this does not mean that they have no sense of smell.

For instance, crabs capture smells through the sensory bristles on their antennae, while snakes, although they do have nostrils, actually smell better through their mouths, "fishing" for scents with their forked tongues.

However, smell and taste usually work together in allowing animals to navigate the world. This collaboration is obvious in snails, for instance, whose lower tentacles allow them to smell and taste their environment.

Taste and smell also work as complementary senses in humans. Olfactory (smell) inputs from the nostrils and gustatory (taste) inputs from the tongue interact in the brain to create a complete picture of what, for example, a person is preparing to eat or drink.

Nevertheless, so far, researchers have tended to believe that the senses of taste and smell operate individually in humans and other mammals.

However, a study that Current Biology published earlier this year found that when scientists removed the taste cortex from the brains of rats, this affected not only the animals' ability to perceive taste but also their sense of smell.

Similar research has now led Dr. Mehmet Hakan Ozdener and colleagues from the Monell Center in Philadelphia, PA, to investigate whether mammals - including humans - can also smell with their tongues.

Taste cells could both taste and smell
First, the researchers found that mouse taste papilla cells actually contained olfactory receptors and that the same was true of the cultured human taste cells.
In the new study, the results of which appear in the journal Chemical Senses, Dr. Ozdener and team used both genetic and biochemical techniques to determine whether the taste buds of mice, called mouse taste papilla cells, might be able to respond to odor molecules. They then tested laboratory cultures of human fungiform taste papilla cells.

Following this, the team used a scientific technique called calcium imaging to assess how the cultured taste cells responded to odor molecules, which revealed that the taste cells interacted with them in a very similar way to regular smell receptor cells.

Further experiments then also showed, for the first time, that one taste cell can contain receptors for both smell and taste. This discovery could help shed new light on just how closely taste and smell work together to alert us to the desirability of a particular food, for instance.

"The presence of olfactory receptors and taste receptors in the same cell will provide us with exciting opportunities to study interactions between odor and taste stimuli on the tongue."

Dr. Mehmet Hakan Ozdener

"Our research may help explain how odor molecules modulate taste perception," Dr. Ozdener also notes, adding that it "may lead to the development of odor-based taste modifiers that can help combat the excess salt, sugar, and fat intake associated with diet-related diseases, such as obesity and diabetes."

In the future, the research team hopes to find out whether only certain taste cells contain smell receptors and to what extent the odor molecules that taste cells capture can change how an individual perceives specific tastes.

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Many animals taste and smell their environment through the same part of their body, but can the same be true about humans? New research suggests that this might indeed be the case and that we may have smell receptors on our tongues.

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https://www.thermofisher.com/uk/en/home/life-science/stem-cell-research/hematopoietic-stem-cells.html?ef_id=EAIaIQobChMIufLn_Nvf5AIVhbHtCh1arg4kEAAYASAAEgIaSvD_BwE:G:s&s_kwcid=AL!3652!3!367765480926!e!!g!!hematopoietic%20cells&gclid=EAIaIQobChMIufLn_Nvf5AIVhbHtCh1arg4kEAAYASAAEgIaSvD_BwE

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Intestinal stem cells (ISCs) are the only dividing cells in the intestinal epithelium that can give rise to at least two differentiated intestinal cell types: enteroendocrine cells and enterocytes.

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Intestinal stem cells (ISCs) are the only dividing cells in the intestinal epithelium that can give rise to at least two differentiated intestinal cell types: enteroendocrine cells and enterocytes.

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https://www.nature.com/subjects/intestinal-stem-cells

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The intestinal epithelium is a rapidly renewing cellular compartment. This constant regeneration is a hallmark of intestinal homeostasis and requires a tightly regulated balance between intestinal stem cell (ISC) proliferation and differentiation. The intestine also meets pathogenic environmental factors that means it must actively repair  constantly

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Is a teratoma a baby?

Sacrococcygeal teratoma (SCT) is a tumor that develops before birth and grows from a baby's coccyx — more commonly known as the tailbone. It is the most common tumor found in newborns, occurring in 1 out of every 35,000 to 40,000 live births.

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Mammary stem cells role in helping suppress teratomas

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Mammary stem cells role in helping suppress teratomas

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https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5223207/