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"Stem cell therapy works by giving the heart a mega dose of its own repair cells"(1).

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He contacted the doctor, Roberto Bolli of the University of Louisville, and in July of that year Jones became the first person in the world to receive an infusion of his own cardiac stem cells.

"Jones was the first to have an infusion of his own cardiac cells by Roberto Bolli"(1)

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Frequently asked questions about stem cell research
Mayo Clinic

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Stem cells: What they are and what they do

Stem cells and derived products offer great promise for new medical treatments. Learn about stem cell types, current and possible uses, ethical issues, and the state of research and practice.
By Mayo Clinic Staff
You've heard about stem cells in the news, and perhaps you've wondered if they might help you or a loved one with a serious disease. You may wonder what stem cells are, how they're being used to treat disease and injury, and why they're the subject of such vigorous debate.

Here are some answers to frequently asked questions about stem cells.

What are stem cells?

Stem cells are the body's raw materials - cells from which all other cells with specialized functions are generated. Under the right conditions in the body or a laboratory, stem cells divide to form more cells called daughter cells.

These daughter cells either become new stem cells (self-renewal) or become specialized cells (differentiation) with a more specific function, such as blood cells, brain cells, heart muscle cells or bone cells. No other cell in the body has the natural ability to generate new cell types.

Why is there such an interest in stem cells?

Researchers and doctors hope stem cell studies can help to:

Increase understanding of how diseases occur. By watching stem cells mature into cells in bones, heart muscle, nerves, and other organs and tissue, researchers and doctors may better understand how diseases and conditions develop.

Generate healthy cells to replace diseased cells (regenerative medicine). Stem cells can be guided into becoming specific cells that can be used to regenerate and repair diseased or damaged tissues in people.

People who might benefit from stem cell therapies include those with spinal cord injuries, type 1 diabetes, Parkinson's disease, amyotrophic lateral sclerosis, Alzheimer's disease, heart disease, stroke, burns, cancer and osteoarthritis.

Stem cells may have the potential to be grown to become new tissue for use in transplant and regenerative medicine. Researchers continue to advance the knowledge on stem cells and their applications in transplant and regenerative medicine.

Test new drugs for safety and effectiveness. Before using investigational drugs in people, researchers can use some types of stem cells to test the drugs for safety and quality. This type of testing will most likely first have a direct impact on drug development first for cardiac toxicity testing.

New areas of study include the effectiveness of using human stem cells that have been programmed into tissue-specific cells to test new drugs. For the testing of new drugs to be accurate, the cells must be programmed to acquire properties of the type of cells targeted by the drug. Techniques to program cells into specific cells continue to be studied.

For instance, nerve cells could be generated to test a new drug for a nerve disease. Tests could show whether the new drug had any effect on the cells and whether the cells were harmed.

Where do stem cells come from?

Researchers have discovered several sources of stem cells:

Embryonic stem cells. These stem cells come from embryos that are three to five days old. At this stage, an embryo is called a blastocyst and has about 150 cells.

These are pluripotent (ploo-RIP-uh-tunt) stem cells, meaning they can divide into more stem cells or can become any type of cell in the body. This versatility allows embryonic stem cells to be used to regenerate or repair diseased tissue and organs.

Adult stem cells. These stem cells are found in small numbers in most adult tissues, such as bone marrow or fat. Compared with embryonic stem cells, adult stem cells have a more limited ability to give rise to various cells of the body.

Until recently, researchers thought adult stem cells could create only similar types of cells. For instance, researchers thought that stem cells residing in the bone marrow could give rise only to blood cells.

However, emerging evidence suggests that adult stem cells may be able to create various types of cells. For instance, bone marrow stem cells may be able to create bone or heart muscle cells.

This research has led to early-stage clinical trials to test usefulness and safety in people. For example, adult stem cells are currently being tested in people with neurological or heart disease.

Adult cells altered to have properties of embryonic stem cells (induced pluripotent stem cells). Scientists have successfully transformed regular adult cells into stem cells using genetic reprogramming. By altering the genes in the adult cells, researchers can reprogram the cells to act similarly to embryonic stem cells.

This new technique may allow researchers to use reprogrammed cells instead of embryonic stem cells and prevent immune system rejection of the new stem cells. However, scientists don't yet know whether using altered adult cells will cause adverse effects in humans.

Researchers have been able to take regular connective tissue cells and reprogram them to become functional heart cells. In studies, animals with heart failure that were injected with new heart cells experienced improved heart function and survival time.

Perinatal stem cells. Researchers have discovered stem cells in amniotic fluid as well as umbilical cord blood. These stem cells also have the ability to change into specialized cells.

Amniotic fluid fills the sac that surrounds and protects a developing fetus in the uterus. Researchers have identified stem cells in samples of amniotic fluid drawn from pregnant women to test for abnormalities - a procedure called amniocentesis.

More study of amniotic fluid stem cells is needed to understand their potential.

Why is there a controversy about using embryonic stem cells?

Embryonic stem cells are obtained from early-stage embryos - a group of cells that forms when a woman's egg is fertilized with a man's sperm in an in vitro fertilization clinic. Because human embryonic stem cells are extracted from human embryos, several questions and issues have been raised about the ethics of embryonic stem cell research.

The National Institutes of Health created guidelines for human stem cell research in 2009. The guidelines define embryonic stem cells and how they may be used in research, and include recommendations for the donation of embryonic stem cells. Also, the guidelines state embryonic stem cells from embryos created by in vitro fertilization can be used only when the embryo is no longer needed.

Where do these embryos come from?

The embryos being used in embryonic stem cell research come from eggs that were fertilized at in vitro fertilization clinics but never implanted in a woman's uterus. The stem cells are donated with informed consent from donors. The stem cells can live and grow in special solutions in test tubes or petri dishes in laboratories.

Why can't researchers use adult stem cells instead?

Although research into adult stem cells is promising, adult stem cells may not be as versatile and durable as are embryonic stem cells. Adult stem cells may not be able to be manipulated to produce all cell types, which limits how adult stem cells can be used to treat diseases.

Adult stem cells also are more likely to contain abnormalities due to environmental hazards, such as toxins, or from errors acquired by the cells during replication. However, researchers have found that adult stem cells are more adaptable than was first thought.

What are stem cell lines and why do researchers want to use them?

A stem cell line is a group of cells that all descend from a single original stem cell and are grown in a lab. Cells in a stem cell line keep growing but don't differentiate into specialized cells. Ideally, they remain free of genetic defects and continue to create more stem cells. Clusters of cells can be taken from a stem cell line and frozen for storage or shared with other researchers.

What is stem cell therapy (regenerative medicine) and how does it work?

Stem cell therapy, also known as regenerative medicine, promotes the repair response of diseased, dysfunctional or injured tissue using stem cells or their derivatives. It is the next chapter in organ transplantation and uses cells instead of donor organs, which are limited in supply.

Researchers grow stem cells in a lab. These stem cells are manipulated to specialize into specific types of cells, such as heart muscle cells, blood cells or nerve cells.

The specialized cells can then be implanted into a person. For example, if the person has heart disease, the cells could be injected into the heart muscle. The healthy transplanted heart muscle cells could then contribute to repairing defective heart muscle.

Researchers have already shown that adult bone marrow cells guided to become heart-like cells can repair heart tissue in people, and more research is ongoing.

Have stem cells already been used to treat diseases?

Yes. Doctors have performed stem cell transplants, also known as bone marrow transplants. In stem cell transplants, stem cells replace cells damaged by chemotherapy or disease or serve as a way for the donor's immune system to fight some types of cancer and blood-related diseases, such as leukemia, lymphoma, neuroblastoma and multiple myeloma. These transplants use adult stem cells or umbilical cord blood.

Researchers are testing adult stem cells to treat other conditions, including a number of degenerative diseases such as heart failure.

What are the potential problems with using embryonic stem cells in humans?

For embryonic stem cells to be useful in people, researchers must be certain that the stem cells will differentiate into the specific cell types desired.

Researchers have discovered ways to direct stem cells to become specific types of cells, such as directing embryonic stem cells to become heart cells. Research is ongoing in this area.

Embryonic stem cells can also grow irregularly or specialize in different cell types spontaneously. Researchers are studying how to control the growth and differentiation of embryonic stem cells.

Embryonic stem cells might also trigger an immune response in which the recipient's body attacks the stem cells as foreign invaders, or the stem cells might simply fail to function normally, with unknown consequences. Researchers continue to study how to avoid these possible complications.

What is therapeutic cloning, and what benefits might it offer?

Therapeutic cloning, also called somatic cell nuclear transfer, is a technique to create versatile stem cells independent of fertilized eggs. In this technique, the nucleus, which contains the genetic material, is removed from an unfertilized egg. The nucleus is also removed from the cell of a donor.

This donor nucleus is then injected into the egg, replacing the nucleus that was removed, in a process called nuclear transfer. The egg is allowed to divide and soon forms a blastocyst. This process creates a line of stem cells that is genetically identical to the donor's cells - in essence, a clone.

Some researchers believe that stem cells derived from therapeutic cloning may offer benefits over those from fertilized eggs because cloned cells are less likely to be rejected once transplanted back into the donor and may allow researchers to see exactly how a disease develops.

Has therapeutic cloning in people been successful?

No. Researchers haven't been able to successfully perform therapeutic cloning with humans despite success in a number of other species.

However, in recent studies, researchers have created human pluripotent stem cells by modifying the therapeutic cloning process. Researchers continue to study the potential of therapeutic cloning in people.

Show references

See more In-depth

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Frequently asked questions about stem cell research

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Stem cells and derived products offer great promise for new medical treatments. Learn about stem cell types, current and possible uses, ethical issues, and the state of research and practice. By Mayo Clinic Staff You've heard about stem cells in the news, and perhaps you've wondered if they might help you or a loved one with a serious disease.

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History of Stem Cell Use: Stem Cells: University of Nebraska Medical Center
UNMC

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Until recently, scientists primarily worked with two kinds of stem cells from animals and humans: embryonic stem cells and non-embryonic "somatic" or "adult" stem cells.

Scientists discovered ways to derive embryonic stem cells from early mouse embryos nearly 30 years ago, in 1981.

The detailed study of the biology of mouse stem cells led to the discovery, in 1998, of a method to derive stem cells from human embryos and grow the cells in the laboratory. These cells are called human embryonic stem cells. The embryos used in these studies were created for reproductive purposes through in vitro fertilization procedures. When they were no longer needed for that purpose, they were donated for research with the informed consent of the donor.

In 2006, researchers made another breakthrough by identifying conditions that would allow some specialized adult cells to be "reprogrammed" genetically to assume a stem cell-like state. This new type of stem cell is now known as induced pluripotent stem cells (iPSCs).

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History of Stem Cell Use | Stem Cells | University of Nebraska Medical Center

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Until recently, scientists primarily worked with two kinds of stem cells from animals and humans: embryonic stem cells and non-embryonic "somatic" or "adult" stem cells. Scientists discovered ways to derive embryonic stem cells from early mouse embryos nearly 30 years ago, in 1981.

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Development of New Technologies for Stem Cell Research
Journal of Biomedicine and Biotechnology

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Since the 1960s, the stem cells have been extensively studied including embryonic stem cells, neural stem cells, bone marrow hematopoietic stem cells, and mesenchymal stem cells. In the recent years, several stem cells have been initially used in the treatment of diseases, such as in bone marrow transplant. At the same time, isolation and culture experimental technologies for stem cell research have been widely developed in recent years. In addition, molecular imaging technologies including optical molecular imaging, positron emission tomography, single-photon emission computed tomography, and computed tomography have been developed rapidly in recent the 10 years and have also been used in the research on disease mechanism and evaluation of treatment of disease related with stem cells. This paper will focus on recent typical isolation, culture, and observation techniques of stem cells followed by a concise introduction. Finally, the current challenges and the future applications of the new technologies in stem cells are given according to the understanding of the authors, and the paper is then concluded.

1. Introduction

Stem cells are a kind of cells that have the ability to perpetuate themselves through self-renewal and to generate functional mature cells of a particular tissue through differentiation [ 1, 2]. So far, stem cells do not have a clear definition which can be used to distinguish them from other cells. However, most of researchers believe that, in general sense, stem cells need to meet the following criteria. First of all, stem cells are capable of continuous, repeated self-renewal divisions in order to maintain the stem cell population. Secondly, a single stem cell can differentiate into a variety of mature cells. Thirdly, stem cells can rebuild the organization when they are transplanted into its source damaged organization. Lastly, even if the tissue does not suffer, stem cells can differentiate into mature cells of the tissue.

In recent years, tumor stem cells increasingly attracted much more attention of researchers. Many researchers found that malignant tumor growth, recurrence, and metastasis were similar to the corresponding characteristics of stem cells [ 1- 3]. With the deepening of research on stem cell and tumor biology, tumor stem cells are initially found in acute myeloid leukemia (AML) [ 4- 8]. Park and his partners had proved that only a small part of the cell subsets of leukemia and multiple myeloma cells have unlimited proliferative capacity, accounting for 1%-4% and 0.001%-1% of the total number of tumor cells, respectively [ 4]. Salmon's group had successfully identified and separated the tumor stem cells with CD34 (+)/CD 38 (−) phenotype from the human acute myeloid leukemia tumor cells for the first time [ 5]. Afterwards, Morrison's and Licht's groups had done some researches on the targets of the AML and this work would surely promote the development of clinical treatment of AML [ 6- 8].

For stem cell research, some technologies are frequently used including stem cell culture, separation, and identification techniques. At present, fluorescence activated cell sorting (FACS) and magnetic activated cell sorting (MACS) are the common separation methods for stem cells. Among them, FACS is the most widely used method. Researchers had obtained the cancer stem cells from breast cancer, brain gliomas, prostate cancer [ 9], gastric cancer [ 10], lung cancer [ 11], liver cancer [ 12], and pancreatic cancer [ 13, 14] using this method. In addition, some cell labeling technique had also been applied in stem cell research. Perrimon's group had labeled the cell using site-specific recombinant technique to randomly activate the lacZ gene in cell population [ 15]. Through labeling some specific gene, function of the stem cell could be detected and identified [ 16]. Lastly, with the advances in microscopy, confocal microscopy techniques have been developed and used to observe the stem cells and their surroundings.

In 1999, Weissleder and his partners proposed the concept of molecular imaging at Harvard University [ 17]. Through 10 years of development, this technology has been widely applied to many aspects of the life sciences. The goal of molecular imaging is to depict noninvasively in vivo cellular and molecular processes sensitively and specifically, such as monitoring multiple molecular events, cell trafficking and targeting [ 18- 20]. In recent years, some new algorithms especially in optical molecular imaging area have been developed, such as multilevel adaptive finite element method [ 18], Bayesian approach [ 21], and graph cuts [ 22]. At the same time, with the advances of hardware and machine technique, some new molecular imaging systems had been developed, such as Spectrum CT of Cold Spring Biotech Corporation with three-dimensional imaging functional. In addition, Cerenkov luminescence imaging (CLI) using Cerenkov theory had been developed to capture the signals derived from ¹⁸ F-FDG probe. Compared to the traditional imaging method, all these imaging technologies had shown its advantage in tumor mechanism and antitumor evaluation research and had been initially applied in the stem cell research.

In this review paper, we will focus on the following three aspects. Firstly, we will introduce some new isolation and culture technology and review its application in stem cell research. Secondly, we will introduce several molecular imaging techniques and review some researchers' work on stem cells using these techniques. Finally, we will predict the future prospects to conclude the paper.

2. New Isolation and Culture Technology and Its Application in Stem Cells Research

Traditional culture methods typically involve reprogramming somatic cells to pluripotency by serial passage under adherent culture conditions on feeder cells or on extracellular matrix compounds [ 25]. The stem cells using these approaches likely to be contaminated by pathogens; these approaches are require separation of feeder cells from the cell type of interest which increase costs and are prone to differentiate variability. In recent years, many new isolation and culture technologies have been developed to obtain stem cells for their wide application prospects in disease mechanism and its treatment including suspension technology [ 23] and SB431542 inhibitor differentiation method [ 24].

2.1. Suspension Technology

Induced pluripotent stem cells (iPSCs) draw more and more attention because of their therapeutic advantages in enabling the generation of high-quality disease models, derivation of individual-specific iPSC lines, improving the predictability of drug action, and as a source of cells for regenerative medicine [ 23]. Zandstra's group had developed a way to obtain induced pluripotent stem cells in continuous adherence- and matrix-free suspension culture system, which has the potential to accelerate and standardize iPSCs research. The gene expression analysis showed high correlation between the two processes including reprogramming in suspension culture and that in routine adherent culture with regard to hallmark reprogramming genes.

2.2. SB431542 Inhibitor Differentiation Method

Mesenchymal stem cells are one kind of adult stem cells, which mainly derived from bone marrow stromal cells. Because of their ability to differentiate into a wide range of mesenchymal-lineage tissues, mesenchymal stem/stromal cells (MSCs) are under intense investigation for applications in cardiac, renal, neural, joint, and bone repair, as well as in inflammatory conditions and hemopoietic cotransplantation [ 24]. MSCs are typically harvested from adult bone marrow or fat, but these methods not only require painful invasive procedures, but also are low-frequency sources, with MSCs making up only 0.001% of bone marrow cells and 0.05% in fat tissues [ 26, 27].

Traditional fetal MSCs isolation method was described in Guillot's paper [ 28]. Briefly, first-trimester fetal bone marrow MSCs were obtained by flushing the bone marrow cells out of humeri and femurs using a syringe and a 22-gauge needle. The resultant cells were allowed to adhere to a standard tissue culture flask for 72 hours in MSC medium. Afterwards, they were washed and passaged with Tryple-Select upon confluence, cultured under humidified conditions in 5% CO ₂, and routinely cryopreserved in 90% FCS and 10% dimethyl sulfoxide (DMSO). Fisk's group had developed a new method to obtain MSCs and this research result would influence deeply a number of patients suffering from serious disease. In their studies, firstly, to develop a feeder cell-free method to produce MSCs from ESCs or iPSCs, they used a widely used commercially available defined medium, mTeSR1(Stem Cell Technologies), which in combination with the cell attachment matrix Matrigel, maintains pluripotency of ESCs/iPSCs without the need for feeder cells or additional basic fibroblast growth factor (bFGF) [ 29]. Then cells were seeded as large colonies at high confluence, and some cell lines required a one-passage adaptation to mTeSR/Matrigel conditions prior to MSC differentiation. When cells were confluent, the medium was changed to inhibitor differentiation medium including knockout serum replacement (KOSR) medium without bFGF, supplemented with 10  μM SB431542(SB) (a kind of transforming growth factor- β) in DMSO. The MSCs could be obtained using this new method in about 10 days, which was more quickly than traditional methods.

In addition to the two new methods developed recently, many researchers had done much work on the isolation and culture technology of stem cells in order to apply it in the treatment of disease more extensively. Fan's group had observed [ 30] that the embryonic stem cells possessed a relatively loose, open chromatin structure, and the differentiated cells possessed a tight chromatin structure. This research demonstrated for the first time that the state of chromatin compaction was not only the result of cell differentiation, but also the cell differentiation needed. Fischbach's group had showed that adipose-derived stem cell could trigger the tumor growth [ 31]. Yamanaka's group had induced pluripotent stem cells from mouse embryonic [ 32] and adult human fibroblasts using defined factors [ 33]. All these studies had promoted the stem cells' application in the treatment of disease including tumor and regenerative medicine.

3. Molecular Imaging Techniques and Their Application in Stem Cell Research

Molecular imaging, including bioluminescence imaging (BLI), fluorescence molecular imaging (FMI), positron emission tomography (PET), single photon emission computed tomography (SPECT), and magnetic resonance imaging (MRI) can characterize and quantify biological process at the cellular and molecular level in intact living subjects. It usually exploits specific molecular probes as the source of image contrast to detect the disease and evaluate drug efficacy [ 34]. In recent years, with the development of molecular imaging including imaging systems and imaging algorithms, molecular imaging has been widely applied in many areas, such as tumor research, drug development, and stem cell research and so on. Take the bioluminescence imaging system as an example, it has been developed from two-dimensional system to three-dimensional systems. Fluorescence imaging system has also been greatly improved in imaging acquisition speed and stability. Meanwhile, many algorithms had been developed to improve the speed and accuracy of image reconstruction, such as Tikhonov regularization method [ 18], a Born-type approximation BLT method [ 35], the Bayesian approach [ 21]. The development in system and algorithm enables molecular imaging to become an important means of stem cell research. Then we will review some researches of molecular imaging on tracking stem cell therapy of cardiovascular and neurological diseases.

3.1. Molecular Imaging for Tracking Stem Cell Therapy in Cardiovascular

Cardiovascular disease is the second cause of morbidity and mortality in China, and the leading cause of morbidity and mortality in the United States [ 38]. One major reason for the high morbidity and mortality is that the heart has an inadequate regenerative response following ischemia caused by myocardial infarction or other chronic cardiovascular diseases [ 39, 40]. Novel regenerative therapies like stem cell therapy can promote neovascularization and neomyogenesis, which need to be evaluated using molecular imaging [ 41, 42].

For cardiac stem cell therapy, Bulte's group monitored the trafficking of ¹¹¹In labeled mesenchymal stem cells after intravenous administration in a porcine myocardial infarction model using SPECT imaging [ 43]. Cao's group demonstrated the utility of BLI by tracking survival and proliferation of mouse ESCs following cardiac injection in rats in 2006 [ 44]. Then Li's group made a head-to-head comparison of BLI and MRI using human ESCs in immunodeficient mouse hind limb models and found that MR images showed stable and similar signals in both undifferentiated ESCs and differentiated endothelial cells for 4 weeks, whereas BLI showed divergent survival profiles for the two groups [ 36]. The result was shown in Figure 1. In addition, Schrepfer's group has used GFP to histologicaly verify the presence of transduced bone marrow mononuclear cells following transplantation into myocardium [ 45]. All these imaging technologies including BLI, FMI, PET, SPECT, and MRI have been used in tracking stem cell therapy in cardiovascular, which will promote the development of stem cell therapy.

3.2. Molecular Imaging for Stem Cell Therapy in Neurological Diseases

The nervous system is a delicate and complex system, composed of neurons, glial cells, microglia, and cells and blood vessels of the meninges. Human neurological diseases such as Alzheimer's disease, Parkinson's disease, Huntington's disease, spinal cord injury, and multiple sclerosis are caused by loss of different types of neurons and glial cells in the brain and spinal cord [ 46]. Discovery of the therapeutic potential of stem cells offers new methods for the treatment of neurological diseases. Advances in imaging equipment and technique offer powerful methods for evaluating therapeutic efficacy of neurological diseases [ 47, 48].

For PET imaging, as a common imaging probe, ¹⁸F-FDG has been used to label porcine circulation progenitor cells with the labeling efficiency % [ 49]. Furthermore, Kang's group has evaluated the efficacy of stem cell therapy in human heart using PET in clinical studies [ 50, 51]. Bjorklund's group has used PET and ¹¹C-labeled 2 β-carbomethoxy-3 β-(4-fluorophenyl) tropane ([ ¹¹C]CFT) to obtain parallel evidence of dopaminergic (DA, associated with Parkinson's disease) cell differentiation in vivo [ 37]. Behavioral recovery of rotational asymmetry at 9 weeks after implantation of ESCs in animal models implicated that ESCs could become a donor source for cell therapy in Parkinson's disease (PD), and the results were shown in Figure 2. Bradbury's group has monitored the long-term viability and proliferation of hESC-derived neural precursor grafts in the brains of immunodeficient and immunocompetent mice using BLI [ 52]. Their studies demonstrated that there was no significant alteration in the viability of transduced hESC-derived neural precursors in immunodeficient models over a 2-month period, but there were variations in proliferative activity among grafted animals. These studies indicate the broad application prospects of molecular imaging techniques in stem cell therapy for nervous disease.

4. Conclusions and Future Prospects

As we know, stem cells have the following features. First, self-renewal is the hallmark property of stem cells in normal and diseased tissues. Second, the cells that continue to divide over long periods of time are much more likely to accumulate mutations that cause neoplasia and other diseases. Third, in normal tissues that contain self-renewing stem cells, such as the epithelia, the genetic changes which may cause tumorigenesis probably also occur in the stem cells or in progeny that acquire the potential for self-renewal [ 1]. Finally, self-renewing of stem cell is controlled by distinct signaling pathways in different tissues. All the characters of stem cells promote the researches on culture, isolation, clinical application, and other related technologies.

In recent years, many isolation and culture technologies have been proposed, which are reviewed in the above sections. These technologies have promoted the application of the stem cells on research of disease mechanism and clinical therapy. However, most types of stem cells have their own disadvantages for therapeutic applications, such as lack of availability, risk of immune rejection, directional regulation, and ethical controversy. The recent discovery of iPSCs holds the potential to solve these problems. However, the low efficiency of iPSCs generation and their therapeutic safety need to be further studied before initiation of human clinical trials [ 53, 54]. The speed and efficiency of iPSCs generation from both mouse and human somatic cells can be enhanced by adding vitamin C to the culture medium [ 55] and the safety of iPSCs may be improved by using nonintegrating viral vectors [ 56, 57]. Therefore, we expect that clinical application of iPSCs will be achieved in the near future, which will be a historical leap in the medicine area.

To monitor the efficacy of stem cell therapy and develop new isolation and culture technology, it is necessary to improve molecular imaging techniques. For example, new reporter gene systems under development for PET imaging was reported as a new in vivo reporter gene imaging system to monitor transduced ESCs in mice [ 58, 59]. Meanwhile, Cerenkov imaging technology is under development for its equivalence with PET [ 60, 61]. Optical molecular imaging systems are also being improved from both reconstruction accuracy and speed. Furthermore, "Opti-PET" instrumentation that will combine advantages of optical imaging with high resolution, low cost, and quantitation ability of PET is also under development [ 62, 63]. Although none of these imaging technologies fulfill all of the requirements needed for stem cell therapy research at present, their improvement and the development of multimodality molecular imaging system will promote more effectively the understanding of stem cell therapy biology and its mechanisms.

Acknowledgments

This research is supported by the National Basic Research Program of China (973 Program) under Grant no. 2011CB707700, the Knowledge Innovation Project of the Chinese Academy of Sciences under Grant no. KGCX2-YW-907, the National Natural Science Foundation of China under Grant nos. 81071205, 81101095, and 81027002, the Beijing Natural Science Foundation under Grant no. 4111004, the Youth Innovation Promotion Association of CAS, the Fellowship for Young International Scientists of the Chinese Academy of Sciences under Grant no. 2010Y2GA03, and the Chinese Academy of Sciences Visiting Professorship for Senior International Scientists under Grant no. 2010T2G36.

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Development of New Technologies for Stem Cell Research

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Since the 1960s, the stem cells have been extensively studied including embryonic stem cells, neural stem cells, bone marrow hematopoietic stem cells, and mesenchymal stem cells. In the recent years, several stem cells have been initially used in the treatment of diseases, such as in bone marrow transplant.

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Jabr, Ferris. “A Change of Heart.” Scientific American, vol. 308, no. 4, Apr. 2013, pp. 50–52. EBSCOhost, doi:10.1038/scientificamerican0413-50.

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Ohio's PreK-12 Digital Library. Optimized by the Management Council.

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Harvesting semispecialized stem cells from an ailing heart, helping them to make millions of copies of themselves and injecting those cells into the heart enable the organ to break down scar tissue and grow new muscle.

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"Optical molecular imaging, positron emission tomography, single-photon emission computed tomography, and computed tomography have been developed rapidly in recent the 10 years and have also been used in the research on disease mechanism and evaluation of treatment of disease related with stem cells"(1)

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A1
"Stem cells are the body's raw materials — cells from which all other cells with specialized functions are generated"(1).

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"If used directly from the ESC undifferentiated culture prep for tissue transplants, they can cause tumors (teratomas) or cancer development"(3).

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" By watching stem cells mature into cells in bones, heart muscle, nerves, and other organs and tissue, researchers and doctors may better understand how diseases and conditions develop."

"Doctors and researchers watch stem cells as they mature so they can see how diseases might be caused"(1).

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"People who might benefit from stem cell therapies include those with spinal cord injuries, type 1 diabetes, Parkinson's disease, amyotrophic lateral sclerosis, Alzheimer's disease, heart disease, stroke, burns, cancer and osteoarthritis."

Others that can benefit from stem cells are people with irreversible diseases and physical illnesses.

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"Scientists discovered ways to derive embryonic stem cells from early mouse embryos nearly 30 years ago, in 1981"(1).

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"In the 3- to 5-day-old embryo, called a blastocyst, the inner cells give rise to the entire body of the organism, including all of the many specialized cell types and organs such as the heart, lung, skin, sperm, eggs and other tissues."

"In the 3- to 5-day-old embryo, called a blastocyst, the inner cells give rise to the entire body of the organism"(2).