Scientists Develop Technique to Determine Ethnic Origin of Stem Cell Lines

(HealthDay News) The majority of embryonic stem cell research is being conducted on lines that have been established years ago from frozen in vitro fertilization embryos. Many times the ethnic origin of these cells is not known, or when it is, specific issues as to country of origin versus actual ethnicity are not clear.
Scientists at the Scripps Research Institute in La Jolla, California have reported what they believe to be a potential solution to this puzzle. The team, lead by Dr. Jeanne Loring, published a paper in the January 2010 edition of the journal Nature Methods in which they reveal a molecular technique that could be useful for answering this question.

"Ethnic origin is a critical piece of information that should come with every cell line," said Dr. Loring. "Everyone who works with stem cells should be doing this kind of analysis."

Dr. Loring was referring to numerous situations in which different ethnicities have different biological responses to drugs or medical treatments. Although in the majority of cases these differences are subtle, situations such as metabolism of specific drugs or organ rejection can have terrible consequences if ethnicity is not taken into consideration. In the study, Dr. Loring’s team analyzed a variety of human embryonic stem cell lines that are being used in laboratory research internationally. Of these cell lines, the majority originated from donors of Caucasian and East Asian descend, with no representation from Africa.

In order to address this problem, brand new stem cells were generated using the inducible pluripotent stem cell (iPS) method from a donor of West African Yoruba origin. This cell line was the first pluripotent cell line to have the genetic make-up of a person from this ethnic group. The iPS technology essentially allows for the generation of cells that resemble both functionally, and molecularly embryonic stem cells without the need for using fertilized eggs. Scientists have previously reported that introduction of certain genes into skin cells, or other types of adult cells, can be used to "de-differentiate" adult cells into a phenotype that resembles embryonic stem cells. By being able to take adult cells and generated cells that resemble embryonic stem cells, scientists such as Dr. Loring have made pluripotent stem cell lines not only from humans of different ethnicities, but also individuals with various diseases, as well as animals at risk of extinction.

"Knowing that a big push in the future is using these lines in the clinic and in drug development, there’s a need to have an ethnically diverse population of cells," added Louise Laurent, M.D., Ph.D., assistant professor at the University of California, San Diego (UCSD) and research associate at Scripps Research, who is first author of the paper with Caroline Nievergelt, Ph.D., also an assistant professor at UCSD.

The current research was based on a previously described molecular biology technology in which specific gene signatures are correlated with ancestry of individuals. On such project, the International HapMap Project, was published in the journal Nature in 2003. This effort linked single-letter alterations in the genetic code — known as single nucleotide polymorphisms, or SNPs — with people of known ethnic origins. This data provided a way to identify the ethnic heritage of a donor of any cell.
"There’s not a lot of value in making a new pluripotent stem cell line now unless it has something new to offer," said Loring. "I think that increasing ethnicity and genetic diversity is an important reason for generating new lines."

"Essentially this publication represents a shift in our thinking about stem cells. Initially the major issue in stem cell research has been how to generate different tissues, now scientists are beginning to take it for granted that tissue generation is occurring and the next issues of transplantation, matching, and scale-up are being considered".

Stem Cells Might Reverse Heart Damage From Chemo

One of the great findings of regenerative medicine was that organs previously believed to be incapable of healing themselves actually contain stem cells that in response to injury cause some degree of healing. The problem being that these "endogenous healing mechanisms" are usually too small to mediate effects that are visible at the clinical level. For example, the brain was considered to have very limited ability to heal itself after damage. Recent studies that have allowed for observation of brain cells after experimental strokes have led to the discovery of brain stem cells in the dendate gyrus and subventricular zones of the brain, stem cells that start to multiple after a stroke. Interestingly, various hormones such as human chonrionic gonadotropin, are capable of stimulating brain stem cell multiplication. This is currently being used in clinical trials for stroke by the company Stem Cell Therapeutics.

In the area of heart failure, it was also believed that once cardiac tissue is damaged, the only repair process that the body performs is production of scar tissue, which is pathological to the patient. While this scar tissue is found in the majority of the injured area, molecular studies have revealed the existence of cardiac specific stem cells, which start to multiply after injury and serve to repair, albeit in small amounts, the infarct area.

One way to augment endogenous repair processes is to administer stem cells from the bone marrow, which are known to produce various growth factors that assist the tissue-specific stem cell in mediating its activity. Another way is to physically extract the tissue specific stem cells, expand them outside of the body and reimplant them into the damaged area.

In a recent publication in the journal Circulation, Piero Anversa, M.D., director, Center for Regenerative Medicine, Departments of Anesthesia and Medicine and Cardiovascular Division, Brigham and Women’s Hospital, Boston and Roberto Bolli, M.D., chief, cardiology, and director, Institute of Molecular Cardiology, University of Louisville, Kentucky, describe the use of cardiac specific stem cells in treatment of animals whose hearts of been damaged by the chemotherapeutic drug doxorubicin.
Doxorubicin is a chemotherapeutic drug that is mainly used in the treatment of breast, ovarian, lung, and thyroid cancers, as well as for neuroblastoma, lymphoma and leukemia. One of the main limiting factors to increasing the dose of doxorubicin to levels that can lead to tumor eradication is that it causes damage to the heart muscle, the myocardium.

In the published study, the investigators expanded the cardiac specific stem cells from rats, gave the rats high doses of doxorubicin and in some rats injected back cardiac specific stem cells, whereas other rats received control cells. The rats that received the cardiac specific stem cells had both preservation of cardiac function, and also regeneration of the damaged heart tissue. This is an important finding since the type of damage that doxorubicin does to the heart is different from other types of heart damage that have been studies, such as the damage that occurs after a heart attack. These data seem to suggest that stem cell therapy may be useful in a variety of injury situations.

"Theoretically, patients could be rescued using their own stem cells," said study author Dr. Piero Anversa, director of the Center for Regenerative Medicine at Brigham and Women’s Hospital in Boston. Dr. Aversa is one of the original discoverers of the cardiac specific stem cell when he published experiments in dogs demonstrating multiplication of cells in the myocardium that seem to have ability to generate new tissue after damage (Linke et al. Stem cells in the dog heart are self-renewing, clonogenic, and multipotent and regenerate infarcted myocardium, improving cardiac function. Proc Natl Acad Sci U S A. 2005 Jun 21;102(25):8966-71).

"A Phase 1 clinical trial using a similar procedure in people is already under way", said Dr. Roberto Bolli, chief of cardiology and director of the Institute of Molecular Cardiology at the University of Louisville in Kentucky, who is heading the trial. The FDA has approved a Phase I clinical trial using cardiac specific stem cells in 30 patients who have congestive heart failure due to disseminated atherosclerosis. "In the trial, participants’ cardiac tissue will be harvested, the stem cells isolated and then expanded in vitro from about 500 cells to 1 million cells over several weeks", Bolli explained. "Several months after the patient has undergone bypass surgery, the stem cells will be re-injected." A similar clinical trial is being performed at Cedars Sinai in Los Angeles.

While the problems of tissue extraction (which is performed by an invasive procedure requiring biopsy of heart tissue) and cost of expansion are still formidable hurdles to widespread implementation, it is believed that the clinical evidence of a therapeutic response will open the door to other avenues of expanding tissue specific stem cells, such as administration of growth factors that can accomplish this without need for cell extraction outside of the body.

Stem Cell as Anti-Aging “Medicine”

Medistem Inc issued a press release describing a collaborative publication between the University of California San Diego, Indiana University, University of Utah, the Dove Clinic for Integrative Medicine, Biotheryx, NovoMedix, The Bio-Communications Research Institute, The Center for Improvement of Human Functioning International and Aidan Products, discussing the contribution of circulating endothelial cells to prevention of aging. The publication also provided data showing that healthy volunteers who have been administered the food supplement Stem-Kine had a doubling of circulating endothelial progenitor cells.

The paper "Circulating endothelial progenitor cells: a new approach to anti-aging medicine?" is freely accessible. "Numerous experiments and clinical trials have been published describing the importance of these repair cells that the body possesses to heal internal organs," stated Dr. Doru Alexandrescu from Georgetown Dermatology, a co-author of the publication. "However, to our knowledge, this is the first comprehensive blueprint in the peer-reviewed literature of how this knowledge may be applied to the question of aging."

The paper summarizes publications describing correlations between decline of circulating endothelial cells and aging/deterioration of several organ systems. The main hypothesis of the publication is that the bone marrow generates a basal number of circulating endothelial cells that serve to continually regenerate the cells that line the blood vessels. Many diseases that are prevalent in aging such as Alzheimer’s are associated with dysfunction of the blood vessel’s ability to respond to various stimuli. This dysfunction is believed to be caused by diminished numbers of circulating endothelial progenitor cells.

Other conditions such as peripheral artery disease are also associated with reduction in this stem cell population, however, when agents are given that increase the numbers of these cells, the degree of atherosclerosis-mediated pathology is decreased. This was demonstrated in a study that administered the drug GM-CSF, which causes an increase in circulating endothelial progenitor cells in a manner similar to Stem-Kine. Unfortunately, drugs currently on the market that have this ability are very expensive and possess the possibility of numerous side effects. The Stem-Kine food supplement is sold as a neutraceutical and is made of natural ingredients that have already been in the food supply.

Another interesting point made by the paper was that the body modulates the number of circulating endothelial progenitor cells based on need. In stroke, the number of circulating endothelial progenitor cells markedly increases in response to the brain damage. Patients in which a higher increase is observed are noted to have a higher chance of recovery. Therapeutic interventions that contain endothelial progenitor cells such as administration of bone marrow cells after a heart attack, are believed to work, at least in part, through providing a cellular basis for creation of new blood vessels, a process called angiogenesis.

Patients with inflammatory conditions ranging from chronic heart failure, to type 2 diabetes, to Crohn’s disease are noted to have a reduction in these cells. The reduction seems to be mediated by the inflammatory signal TNF-alpha. Studies reviewed in the paper describe how administration of antibodies to TNF-alpha in patients with inflammatory conditions results in a restoration of circulating endothelial progenitor cells.

In addition to the possible use of Stem-Kine for restoration/maintenance of circulating endothelial progenitor cells, the publication discusses the possibility of using such cells from sources outside of the body, for example cord blood. Although it was previously thought that cord blood can be used only after strict HLA matching, recent work supports the idea that for regenerative medicine uses, in which prior destruction of the recipient immune system is not required, cord blood may be used without immune suppression or strict tissue matching. This is discussed in the following paper: Cord blood in regenerative medicine: do we need immune
suppression?
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Adenosine inhibits chemotaxis and induces hepatocyte-specific genes in bone marrow mesenchymal stem cells

Bone marrow cells contain several populations that are useful for regenerating injured/aged tissue. These cells include hematopoietic stem cells, mesenchymal stem cells, endothelial progenitor cells, and some argue, progenitor cells left over from embryonic periods that are still capable of differentiating into numerous injured tissue. It has been known for some time that bone marrow cells are capable of treating liver failure both in vitro and in early clinical trials, as can be seen on this video: Stem Cell Therapy for Liver Failure. Other types of stem cells useful for treatment of liver failure, such as cord blood stem cells, may be seen on this video: Cord Blood and Bone Marrow Stem Cells for Liver Failure.

One of the major questions with adult stem cell therapy is how do the stem cells go to where they are needed? Some people have made the argument that stem cells administered intravenously do not cause systemic effect because the majority get stuck in the lung and liver. Although cell sequestration is an issue, numerous studies have demonstrated therapeutic effects after intravenous administration of stem cells. Perhaps the most well-known stem cell homing molecule is stromal derived factor (SDF-1), which is made by injured and/or hypoxic tissue and causes stem cell mobilization and migration through activation of the CXCR4 receptor. The SDF-1/CXCR4 axis has been found in numerous conditions of tissue injury such as: stroke, heart attack, acoustic injured ear, liver failure, and post-transplant reconstitution of bone marrow. To understand how this “chemokine” works, the following video will describe it as relevant to stem cell repopulation post-irradiation: Homing of Stem Cells to Target Tissue

In a study published today scientists examined another signal made by injured tissue in order to assess whether it may act like SDF-1 and “call in” stem cells. The signal chosen was the amino acid adenosine, which is released from injured/necrotic cells. They found that adenosine did not by itself induce chemotaxis of mesenchymal stem cells (MSC) but dramatically inhibited MSC chemotaxis in response to the chemoattractant hepatocyte growth factor (HGF). Inhibition of HGF-induced chemotaxis by adenosine requires the A2a receptor and is mediated via up-regulation of the cyclic adenosine monophosphate (AMP)/protein kinase A pathway. Additionally, the investigators found that adenosine induces the expression of some key endodermal and hepatocyte-specific genes in mouse and human MSCs in vitro.

The ability of adenosine to modulate migration/differentiation processes implies that numerous paracrine/autocrine interactions are occurring during tissue injury. It will be critical to identify how to manipulate such factors to obtain maximal therapeutic responses.

Athersys May Get Up To $111M from Pfizer In Stem-Cell Deal

Classically Big Pharma has been focused on development small molecule drugs that can be readily made en masse, and whose chemistry is well understood. Biologics such as antibodies have also been gaining popularity, albeit at a slower rate. Stem cells are more difficult than biologics in terms of manufacturing, however, despite this, there has been some increasing interest by Big Pharma in this area in the last couple years. For example, in June 24th, 2008 Pfizer provided Series A funding for EyeCyte, a San Diego company dedicated to generating cell based treatments for diabetic retinopathy. A mega-deal between Osiris Therapeutics and Genzyme worth over a billion dollars was signed on Nov 4, 2008 for the rest of world rights for the mesenchymal stem cell products Prochymal and Chondrogen.

On August 7, 2009 Opexa and Novartis signed a $50 million deal involving a $4 million upfront payment for a pre-clinical stem cell technology. More recently, Pfizer signed a deal worth $111 million with Athersys involving development of the MultiStem product in the area of inflammatory bowel disease.

"Pfizer is committed to the development of new medicines that have the potential to fundamentally improve the quality of clinical care in areas of need. We are delighted to work with Athersys to develop MultiStem for inflammatory bowel disease," said Dr. Ruth McKernan, Head of Pfizer Regenerative Medicine. "This is an innovative new area and our collaboration with Athersys represents a cornerstone of Pfizer’s stem cell and regenerative medicine strategy."

Athersys is a clinical stage biopharmaceutical company that is developing both stem cell and non-stem cell based drugs. Its Regenerative medicine pipeline includes the use of MultiStem for acute myocardial infarction, bone marrow transplant support, and ischemic stroke. Its small molecule drug pipeline contains novel pharmaceuticals to treat indications such as obesity, as well as certain conditions that affect cognition, attention and wakefulness.

The MultiStem product is a mesenchymal-like stem cell that is capable of becoming numerous types of tissues including heart, brain, muscle, and blood vessels. As found for mesenchymal stem cells derived from other sources, the MultiStem product does not require matching with the recipient. This allows for cells to be used as "universal donor" or a "one size fits all" approach.

"We have been systematically evaluating potential partnering opportunities in multiple areas, and we believe that Pfizer represents the ideal partner for this program," said Dr. Gil Van Bokkelen, Chairman and Chief Executive Officer at Athersys. "Their longstanding global leadership in development and commercialization of new medicines, focus on best-in-class therapies, and their growing commitment to regenerative medicine provide a great foundation for working together."

Stem-Cell Activators Switch Function, Repress Mature Cells

One of the mysteries of stem cell biology is how these cells can on the one hand make copies of themselves (called self-renewal), and depending on the needs of the body, become different cells, a process called differentiation. It is known that the process of differentiation is dependent on various chemical signals. For example, if one climbs on a mountain, the lack of oxygen stimulates cells within the kidney to make the hormone erythropoietin which increases the number of bone marrow stem cells that differentiate into red blood cells. While some of the signaling proteins are known, the effector proteins inside the stem cell that dictate its activity are still not very well understood.

In two recent back-to-back publications in the Dec 17 issue of Nature, some progress was reported in the understanding of stem-cell growth and differentiation. It was demonstrated that there exist three critical proteins which first stimulate stem cells to proliferate. Then, as the cells differentiate into their final cell type, these proteins switch function and arrest the cells from dividing any more. Because of their central role, the proteins could offer a safe and novel therapeutic target in many cancers. The proteins that arrest the multiplication of the cell may be considered as "tumor suppressor" proteins.

The published study, which was led by researchers at the Ohio State University Comprehensive Cancer Center-Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, demonstrated that three proteins, called E2f1, E2f2 and E2f3, play a fundamental role in the differentiation steps that stem cells undergo as they lose their self-renewal activity. One of the interesting findings of the studies was the importance of the Rb tumor suppressor protein in blocking self-renewal of stem cells that are differentiating.

"We show that these E2fs are gene activators in stem cells but then switch to gene repressors when stem cells begin differentiating," says Gustavo Leone, associate professor of molecular virology, immunology and medical genetics at Ohio State’s James Cancer Hospital and Solove Research Institute. Leone headed the first of the two Nature studies and is a co-author on the second.

"This is a very important step in the process of differentiation," Leone says. "As organs form during development, there comes a time when their growth must stop because an organ needs only a certain number of cells and no more. The switch by these proteins from activators to repressors is essential for that to happen. Before this, there was no suspicion that these regulatory proteins had any role in differentiated cells," says Leone. "It was thought they were important only in proliferating cells like stem cells. But that’s not true."

Another interesting finding was that the E2f1, E2f2 and E2f3 proteins, while being inhibited in differentiated cells, can actually be re-activated in the presence of mutated tumor suppressor genes and lead to unrestricted cell growth. This provides another method of generating cancer cells in vitro for testing.

Stem Cell Therapy Aids the Return of Lava Man

Lava Man is a race horse that has had quite a career: he has earned more than $5.2 million and was considered one of the top racehorses in North America. Unfortunately, the recent past has not been to kind to him. Last year he finished last in the 2008 Eddie Read Handicap at Del Mar, and previous to that he has lost a series of six races in a row. Lava Man had arthritis in the joints in his ankles and a small fracture in his left front leg, Being 7 years old at that time, his owners decided it was time for Lava Man to retire.

However it seems like Lava Man’s fortunes may have changed. 17 months after his last race, he is scheduled to make a come-back this Saturday at Hollywood Park in the Native Diver Handicap. The horse was treated with his own fat derived stem cells by Dr. Doug Herthel, who stated:

"The trainer is the only one who can tell you how he’s going to run Saturday, but as far as the way he looks and based on our experience with other horses, theoretically, he should be much better than he was," said Dr. Doug Herthel, who treated Lava Man at the Alamo Pintado Equine Medical Center in Los Olivos, Calif.

"We think of those stem cells as little paramedics," Herthel said. "They go in and they help; they enhance the health of the cartilage." Dr. Herthel stated that significant improvements have occurred in Lava Man following stem cell therapy. He also stated that if Lava Man makes a triumphant return due to stem cells, this would not be the first case of this occurring. He cited the example of Ever A Friend , a 6-year-old horse, who was injured in May 2008, received the same type of fat derived stem cells as Lava Man and returned to win an allowance race and finish second in the Grade I Citation Handicap.

The fat derived stem cells that are being used in the treated of horses appear to work through several mechanisms. On the one hand they can become new cartilage and bone tissue directly, while on the other hand the stem cells producing various growth factors that accelerate the process of healing. Another method, that is more debated amongst scientists, is that the stem cells can actually produce enzymes that degrade scar tissue and allow replacement with functional tissue.

Human use of fat stem cells has been performed for multiple sclerosis (Riordan et al. Non-expanded adipose stromal vascular fraction cell therapy for multiple sclerosis. J Transl Med. 2009 Apr 24;7:29) and is currently being investigated for other conditions such as heart failure and rheumatoid arthritis.

Effort to Regenerate Injured Spinal Cords Turns to a New Model

The salamander has incredible regenerative ability. In addition to ability to grow back severed limbs, salamanders have profound plasticity of neurons and can regrow severed nerve endings at a much higher efficiency than mammals. Given that we live in an age where every gene of the body is known (genomics), almost every major protein is sequenced (proteomics), and more recently the majority of small molecules have been elucidated (metabolomics), one of the major pushes in research is to use this knowledge to understand old mysteries such as the regenerative ability of salamanders.

A multi-institutional scientific team in cooperation with the University of Florida McKnight Brain Institute’s Regeneration Project received a $2.4 million National Institutes of Health Grand Opportunity grant to study regenerative process of the Mexican axolotl salamander with the aim of applying biological lessons learned to spinal cord injury.

Dr. Edward Scott principal investigator for the collaborative grant and director of the McKnight Brain Institute’s Program in Stem Cell Biology and Regenerative Medicine stated "The axolotl is the champion of vertebrate regeneration, with the ability to replace whole limbs and even parts of its central nervous system. These salamanders use many of the same body systems and genes that we do, but they have superior ability to regenerate after major injuries. We think that studying them will tell us a lot about a patient’s natural regenerative capacities after spinal cord injury and nerve cell damage."

Discoveries in other species have been a critical part of biomedical research. For example, the process of RNA interference, which won the Noble Prize in Medicine for 2006 was actually discovered as a phenomena in Petunia Flowers. The toll-like receptors, which revolutionized medical knowledge of how the immune system works were originally identified in fruit flies. The current project seeks to find molecules associated with regeneration and to attempt to replicate them first in animals and subsequently in humans.

The multidisciplinary "Regeneration Project" team is also supported by private foundations such as the Thomas H. Maren Foundation and the Jon L. and Beverly A. Thompson Research Endowment, the UF Office of the Vice President for Research, and an anonymous donor.

Sickle-cell disease can be cured with stem-cell transplant procedure

Sickle cell anemia is a genetic disorder that affects approximately 80,000 Americans, primarily of African-American origin. It is characterized by defective production of red blood cells which makes them extremely fragile and not capable of fully transporting oxygen.

In the December 10th issue of the New England Journal of Medicine a report describing a clinical trial performed at the Clinical Center of the National Institutes of Health in Bethesda, was published that described successful treatment of 9 out of 10 adults suffering from this condition.

"This trial represents a major milestone in developing a therapy aimed at curing sickle cell disease," said NIDDK Director Griffin P. Rodgers M.D. "Our modified transplant regimen changes the equation for treating adult patients with severe disease in a safer, more effective way."

The use of stem cell transplantation for genetic conditions is now becoming increasingly commonplace. For example, cord blood stem cells have been used to treat conditions such as Krabbe Disease, which is a lethal metabolic abnormality. The reason that the current study is so important was that it used a type of "conditioning regimen" that was substantially less toxic than previously performed.

In an older study about 200 children with severe sickle cell disease were cured with bone marrow transplants after receiving high doses of chemotherapy. That protocol was too toxic for adults, whose organs are damaged from the prolonged exposure to abnormal red blood cells and their breakdown products. The current treatment method is applicable to adults.

Stem cell transplantation for conditions like leukemias require the recipient bone marrow to be destroyed prior to administration of the new stem cells. In conditions such as sickle cell, one does not need to completely destroy the recipient bone marrow but merely to replace it with enough healthy stem cells so as to produce sufficient quantities of healthy red blood cells. Although this has theoretically been discussed in sickle cell anemia, to date, the current study is the first one to actually demonstrate this. It is anticipated that future studies of this sort will be conducted to attempt treatment of other metabolic abnormalities.

Brain tumor radiation resistance defeated

One of the biggest challenges to the treatment of cancer is overcoming the ability of cancer cells to become resistant to drugs or radiation. The problem of resistance is particularly relevant in brain cancers called gliomas. Research published in the Journal Stem Cells reports one method of overcoming this problem.

Scientists at Duke University and the Cleveland Clinic claim to have identified molecules associated with the ability of certain cells within a glioma, called tumor stem cells, to resist radiation. Specifically, they have identified a protein called "Notch", which is normally involved in embryonic development, that seems to be selectively found in resistant cells. Using genetic engineering methods they have made cells that were previously sensitive to radiation to become resistant by inducing expression of Notch.

Dr. Jialiang Wang of Duke University, who is the lead author of the study. said the finding marked the first report that Notch signaling in tumor tissue is related to the failure of radiation treatments.

"This makes the Notch pathway an attractive drug target," Wang said. "The right drug may be able to stop the real bad guys, the glioma stem cells."
The authors have also demonstrated that by inhibiting activity of the Notch protein, through administration of chemicals known as gamma-secretase inhibitors, can result in making resistant cells sensitive to radiation.

These findings are interesting in light of another very recent publication (Zhen et al. Arsenic trioxide-mediated Notch pathway inhibition depletes the cancer stem-like cell population in gliomas. Cancer Lett. 2009 Dec 3) in which the anti-leukemic drug Arsenic Trioxide was also demonstrated to alter glioma stem cells through manipulation of the Notch pathway. Notch has been found in numerous other types of tumor stem cells such as breast, colon, lung, and prostate cancer. The expression of a protein in cancer cells that is supposed to be only expressed during embryonic development supports the theory that during formation of cancer, mature cells tend to revert to an embryonic-like phenotype. This is also exemplified by the fact that adding cancer genes (oncogenes) in combination with some specific proteins can take an adult skin cell and transform it into a cell that resembles the embryonic stem cell, called an "iPS" cell. This is described in the following video:

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