Liver: Stem Cell Updates and News
2012

2011-Archives

Top 10 stem cell predictions for 2012: Science, CIRM, ACT, trends
Each year at this time I start thinking about what the next year will bring for the stem cell field. This year is no different and I’ve been pondering what 2012 has in store for us.  You can read my predictions for 2011 here and see how I fared. Not too bad, but overly optimistic I’m afraid about trans-differentiation.

Of course in a way, calendar years are meaningless for science since it proceeds with its own rapid pacing regardless of any arbitrary indicators of the passage of time, but like most of us I still like to use years as times to mark milestones and predict what’s ahead.

In that spirit, here is my list of the top 10 predictions for the stem cell field in 2012. It’s a mixture of good news and bad news...Continue Reading Here.....

Stem Cell Awards for 2011
Now it is time for our 2011 stem cell awards. These awards reflect my opinions and those not mentioned will hopefully forgive me as there is an amazing array of great people and resources..Continue Reading....

Video - Dr. Sang-Mo Kang, UCSF transplant surgeon, discuses recent advancements in stem cell research that may lead to the regeneration of tissues and organs. Series: "UCSF Osher Mini Medical School for the Public" [11/2011] [Health and Medicine] [Show ID: 22563]
Uploaded by UCtelevision 


 What Organ Shortage? Just Make Your Own! Stem Cells and Organ Engineering

Also See; Recommended Blogs

Dec 2011

New stem cell method makes lots of liver, pancreas precursors
Dec 1 2011
Scientists in Canada have overcome a key research hurdle to developing regenerative treatments for diabetes and liver disease with a technique to produce medically useful amounts of endoderm cells from human pluripotent stem cells. The research, published in Biotechnology and Bioengineering, can be transferred to other areas of stem cell research helping scientists to navigate the route to clinical use known as the ‘valley of death’.

“One million people suffer from type 1 diabetes in the United States, while liver disease accounts for 45,000 deaths a year,” said Dr Mark Ungrin from the University of Toronto. “This makes stem cells, and the potential for regenerative treatments, hugely interesting to scientists. Laboratory techniques can produce thousands, or even millions, of these cells, but generating them in the numbers and quality needed for medicine has long been a challenge.”

The research focused on the process of using pluripotent stem cells (PSC) to generate endoderm cells, one of the three primary germ layers which form internal organs including the lungs, pancreas, and liver. The ability to differentiate, or transform, PSCs into endoderm cells is a vital step to developing regenerative treatments for these organs.

“In order to produce the amount of endoderm cells needed for treatments it is important to understand how cells behave in larger numbers, for example how many are lost during the differentiation process and if all the cells will differentiate into the desired types,” said Ungrin.

The team stained cells with fluorescent dye and as the cells divided, the dye was shared equally between the divided cells. By measuring the fluorescence of cell populations at a later stage the team were able to work out the frequency of cell division, which allowed them to predict how many cells would be present in a population at any given time.

This technique allowed the team to detect cell inefficiencies and develop a new understanding of the underlying cell biology during the differentiation of PSCs. This allowed the team to increase effective cell production 35 fold.

“Our results showed significant increases in the amount of endoderm cells generated,” said Ungrin. “This new concept allows us to scale up the production of useful cells, while ensuring PSC survival and effective differentiation.”

Overcoming this bottleneck in research will also help future stem cell researchers navigate the often long and challenging route from laboratory testing to clinical use, and accelerate the time from biomedical advance to beneficial therapy, often referred to as the bench-to-bedside process.

“Most research in this field focuses on the purity of generated cell populations; the efficiency of differentiation goes unreported,” concluded Dr Ungrin. “However our research provides an important template for future studies of pluripotent stem cells, particularly where cells will need to be produced in quantity for medical or industrial uses.”


Oct 2011

Johns Hopkins researchers have developed a way to stimulate stem cells in rats after a liver transplant as a means of preventing rejection of the new organ without the need for immunosuppressant drugs.
A new technique for organ transplants may eliminate the need for lifelong anti-rejection drugs after surgery, according to a recent study.
Johns Hopkins researchers have developed a way to stimulate stem cells in rats after a liver transplant as a means of preventing rejection of the new organ without the need for immunosuppressant drugs.
Anti-rejection medicines carry serious side effects and are a major obstacle to long-term survival of people who require organ transplants.
The study found that a combination of two drugs lengthened survival time and prevented liver rejection in rodents. One drug was a low dose of tacrolimus, which prevented immediate rejection of the transplant, and the other was plerifaxor, which freed the recipient's stem cells from the bone marrow.
The bone marrow cells freed by plerifaxor then traveled to the damaged liver and repopulated it with the recipients’ own cells, replacing the donor cells that cause rejection. The stem cells also appeared to control immune response by increasing the amount of regulatory T-cells.
Essentially, the scientists said they transformed the donor liver from a foreign object under attack by the immune system into an organ tolerated by the body within three months of the surgery.
And – the rats only had to take the medications for one week after the transplant.
The researchers are also testing the method on other transplanted organs, including kidneys, in rats and other larger animals. They hope to begin testing in humans within a few years.
"It is the dream for all scientists in the transplant field to erase the need for lifelong immunosuppressant drugs," said Dr. Zhaoli Sun, an associate professor of surgery at the Johns Hopkins University School of Medicine.
"Currently, if a patient survives for 10 or 20 years with a new liver, that organ is still seen as foreign inside its new body because immunosuppression puts blinders on the immune system that must stay on to prevent rejection. Our idea was to find a way to turn that organ into something that 'belongs' and is never at risk of rejection."
The study was published in the American Journal of Transplantation.

Scientists turn liver cells directly into neurons with new technique
BY KRISTA CONGER
Fully mature liver cells from laboratory mice have been transformed directly into functional neurons by researchers at the Stanford University School of Medicine. The switch was accomplished with the introduction of just three genes and did not require the cells to first enter a pluripotent state. It is the first time that cells have been shown to leapfrog from one fundamentally different tissue type to another.

The accomplishment extends previous research by the same group, which showed in 2009 that it is possible to directly transform mouse fibroblasts, or skin cells, into neurons.

“These liver cells unambiguously cross tissue-type boundaries to become fully functional neural cells,” said Marius Wernig, MD, PhD assistant professor of pathology and a member of Stanford’s Institute for Stem Cell Biology and Regenerative Medicine. “Even more surprising, these cells also simultaneously silence their liver-gene expression profile. They are not hybrids; they are completely switching their identities.”

The cells make the change without first becoming a pluripotent type of stem cell — a step long thought to be required for cells to acquire new identities.

Wernig is the senior author of the research, published online Sept. 29 in Cell Stem Cell. Postdoctoral scholar Samuele Marro, PhD, is the first author of the study.

Related News

• » Scientists turn human skin cells directly into neurons, skipping iPS stage
• » Dramatic transformation: Researchers directly turn mouse skin cells into neurons, skipping IPS stage

The researchers used a technique developed by Stanford bioengineer Stephen Quake, PhD,
to analyze the gene expression profiles of individual hepatocytes (liver cells) and fibroblasts to show that both types of transformed cells not only begin looking and acting like true neurons, they also decisively shut down nearly all gene expression associated with their former, very different identities.

“This is fascinating,” said Wernig. “We can imagine ways that the three introduced factors could stimulate neural gene expression, but how do they also down-regulate two completely unrelated donor networks — those of skin and liver cells?”

Understanding how this down-regulation works will help scientists and clinicians determine whether these so-called transdifferentiated cells can be used to learn more about diseases or even be safely used in human therapy. It would not be good, for example, if newly derived neurons began to again express skin or liver proteins. It also may help researchers understand the process of development, during which cells commit to certain fates while also turning off other potential pathways.

Wernig and Marro began investigating whether hepatocytes could transform into neurons because the fibroblasts they first transformed into neurons in 2010 are a notoriously messy groups of cells. Fibroblasts can be found in almost any organ in the body and contain mixtures of cell types. This made it extremely difficult to identify a cell-of-origin for the resulting neurons and to figure out exactly how big of a developmental leap the cells were making.

In contrast, hepatocytes are fairly homogenous and well-defined. Developmentally speaking, they are also worlds away from neurons: Hepatocytes arise from one of three classes of embryonic tissue called the endoderm; neurons from the ectoderm. The remaining tissue, the mesoderm, is, for the most part, sandwiched between the two. To put it simply: Your innards mostly arise from endoderm, your nervous system and the outer layer of your skin from ectoderm, and your connective tissue and muscles from mesoderm. Transforming endodermal cells into ectodermal cells is a testament to the power of the transdifferentiation technique.

To accomplish the transformation of the hepatocytes, the researchers used a virus to introduce the same three genes that they used for the fibroblasts: Brn2, Ascl1 and Myt1l. As with the fibroblasts, the hepatocytes began to exhibit neuronal characteristics within two weeks, and express neuronal genes within three weeks. Simultaneously, the cells began to suppress the expression of liver-specific genes.

Marro and Wernig used a sophisticated cell-labeling technique to confirm that the new neurons had indeed arisen from the former liver cells, and Fluidigm dynamic polyermerase chain reaction assays to analyze gene expression patterns of individual neuronal cells. They found that even “true” neurons express low levels of liver genes in the form of transcriptional noise. However, the newly differentiated neurons did express marginally higher levels of the same genes.

“Although the donor gene program is dramatically shut down, there are some remnants of their former life, like a kind of a memory,” said Wernig. “But the vast majority of expressed genes demonstrate a clear dominance of the neuronal transcription program.” Furthermore, the fact that the newly derived neurons generate electrical signals and form junctions with other neurons, and that they exhibit no residual liver function, indicates that this memory has no functional relevance, according to Wernig.

In addition to Marro and Wernig, other Stanford researchers involved in the study include postdoctoral scholars Zhiping Pang, MD, PhD; Nan Yang, PhD; and Miao-Chih Tsai, PhD; bioinformatician Kun Qu, PhD; professor of dermatology, Howard Chang, MD, PhD; and professor of molecular and cellular physiology Thomas Sudhof, MD.

The research was supported by the New York Stem Cell Foundation, the Stinehart-Reed Foundation, the Ellison Medical Foundation, the Howard Hughes Medical Institute and the National Institutes of Health. Information about Stanford’s Department of Pathology, which also supported the work, is available at http://pathology.stanford.edu.

Oct 2011
New Stem Cell Method Makes Functioning Liver Cells
British scientists have developed a new stem cell technique for growing working liver cells which could eventually avoid the need for costly and risky liver transplants.

A team of researchers led by the Sanger Institute and the University of Cambridge used cutting-edge methods to correct a genetic mutation in stem cells derived from a patient's skin biopsy, and then grew them into fresh liver cells.

By putting the new liver cells into mice, they showed they were fully functioning.

"We have developed new systems to target genes and ... correct ... defects in patient cells," said Allan Bradley, director of the Sanger Institute.

At a briefing about the work, Bradley said the technique -- the first success of its kind -- leaves behind no trace of the genetic manipulation, except for the gene correction.

"These are early steps, but if this technology can be taken into treatment, it will offer great possible benefits for patients," he added.

Stem cells are the body's master cells, the source for all other cells. Scientists say they could transform medicine, providing treatments for blindness, spinal cord and other severe injuries, and new cells for damaged organs.

Research is focused on two main forms—embryonic stem cells, which are harvested from embryos, and reprogrammed cells, also known as induced pluripotent stem cells or iPS cells, which are reprogrammed from ordinary skin or blood cells.

When they were first discovered in 2006, iPS cells looked like a perfect solution to the ethical debate over the use of embryonic stem cells because they are made in a lab from ordinary skin or blood cells. Embryonic stem cells are usually harvested from leftover embryos at fertility clinics and their use is opposed by many religious groups.

But in recent years, concerns have been raised that iPS cells may not be as "clean" or as capable as embryonic cells.

Last year, a group led by Robert Lanza, of the U.S. firm Advanced Cell Technology, compared batches of iPS cells with embryonic stem cells and noticed the iPS cells died more quickly and were much less able to grow and expand.

Correcting mutation

In Wednesday's study, published in the journal Nature, the British team took skin cells from a patient with a mutation in a gene called alpha1-antitrypsin, which is responsible for making a protein that protects against inflammation.

People with mutant alpha1-antitrypsin are not able to release the protein properly from the liver, so it becomes trapped there and eventually leads to liver cirrhosis and lung emphysema. This is one of the most common inherited liver and lung disorders and affects about one in 2,000 people of North European origin, the researchers said.

Having harvested the skin cells, the scientists reprogrammed them back into stem cells and then used a type of "molecular scissor" technique known as a zinc finger nuclease to snip the cells' genome at precisely the right place and insert a correct version of the gene using a DNA transporter called piggyBac.

The leftover piggyBac sequences were then removed from the cells, cleaning them up and allowing them to be converted into liver cells without any trace of residual DNA damage at the site of the genetic correction.

"We then turned those cells into human liver cells and put them in a mouse and showed that they were viable," David Lomas, a Cambridge professor of respiratory biology who also worked on the team, told reporters at the briefing.

Ludovic Vallier, also from Cambridge University, said the results were a first step toward personalized cell therapy for genetic liver disorders. "We still have major challenges to overcome...but we now have the tools necessary," he said.

The researchers said it could be another five to 10 years before full clinical trials of the technique could be run using patients with liver disease. But if they succeed, liver transplants—costly and complicated procedures where patients need a lifetime of drugs to ensure the new organ is not rejected—could become a thing of the past.

"If we can use a patient's own skins cells to produce liver cells that we can put back into the patient, we may prevent the future need for transplantation," said Lomas.


Scientists use cloning to make human stem cells
Oct 05
Reuters) - U.S. scientists for the first time have used a cloning technique to get tailor-made embryonic stem cells to grow in unfertilized human egg cells, a landmark finding and a potential new flashpoint for opponents of stem cell research.

The researchers were trying to prove it is possible to use a cloning technology called somatic cell nuclear transfer, or SCNT, to make embryonic stem cells that match a patient's DNA.

The achievement, published on Wednesday in the journal Nature, is significant because such patient-specific cells potentially can be transplanted to replace damaged cells in people with diabetes and other diseases without rejection by the immune system.

This technique could ignite new controversy because some opponents consider it to be cloning, which they fiercely oppose.

"This paper will be seen as significant both by those who are trying to use SCNT to produce human patient-specific embryonic stem cell lines and by those who oppose human 'cloning' experiments," said Professor Robin Lovell-Badge, a division head at Britain's National Institute for Medical Research.

Stem cells are the body's master cells, the source material for all other cells. Proponents of embryonic stem cells say they could transform medicine, providing treatments for blindness, juvenile diabetes or severe injuries.

Normally, SCNT involves removing genetic material from the nucleus of the host egg cell and replacing it with the nucleus from adult cells, the technique used to clone animals such as Dolly the sheep in 1996. But scientists so far have failed to get these cells to grow and divide beyond a very early stage in humans and non-human primates.

Scientists in this study, led by Dieter Egli and Scott Noggle at The New York Stem Cell Foundation Laboratory in New York, kept the genetic material from the host egg and simply added the nucleus from the adult cells.

"Rather surprisingly -- as this means that they are creating an embryo with too many copies of each chromosome -- these constructs developed well and efficiently to the blastocyst stage (the stage just before implantation, where the embryo is about 80 to 100 cells)," Lovell-Badge said in a statement.

She said the result falls short because the scientists did not obtain useful cell lines, but they may help explain why other techniques have failed.

"This study shows that the conventional approach to somatic cell nuclear transfer is inefficient in humans," said Professor Mary Herbert of Newcastle University and Newcastle Fertility Center.

"While this approach does not in itself provide a solution, it takes us a step closer to understanding where the problems lie," Herbert said.

PAID DONORS

He said the latest study offers a new approach that may allow scientists to compare different techniques of creating these important and powerful cells.

Embryonic stem cells are made from embryos that are just a few days old, but have been a point of controversy for some religious conservatives, who believe the destruction of any human embryo is wrong.

Scientists typically harvest embryonic stem cells from embryos leftover at fertility clinics, but the eggs in this study came from women who were paid around $8,000, roughly the same rate women are paid for egg donations for in-vitro fertilization.

Scientists have debated whether researchers should pay women for eggs used in stem cell research for fear the payments would act as an inducement to women to donate their eggs, a procedure and can take weeks, can cause discomfort and has some risk.

The goal of these studies is to work out the best ways to create cells that are "pluripotent" -- meaning they can be used to form any other kind of cell in the body.

Embryonic stem cells have this capability, but these cells cannot be tailored to match a specific patient's DNA, and treatments made from these cells might face rejection from the body, much like transplanted organs.

In 2006, scientists discovered a new way creating embryonic-like stem cells in the lab using patients' own skin cells and a potent mix of genes or "factors" that can turn back the clock on the adult cells, restoring them to a pluripotent state.

"The goal is to create customized or personalized stem cells that match a particular patient," said Dr. George Daley of the Harvard Stem Cell Institute and Harvard Medical School in a telephone interview.

But recently, several groups of scientists, including Daley's lab, have found that these iPS cells are not exactly the same as embryonic stem cells.

"We are just beginning to learn about this kind of iPS cell. It turns out they harbor a number of genetic problems," Daley said.

He said the latest study offers a new approach that may allow scientists to compare different techniques of creating these important and powerful cells.

Professor Chris Mason, Chair of Regenerative Medicine Bioprocessing, University College London, said the study adds to the growing number of options for future cell therapies.

"Which approach is the best? Only time will tell, but multiple routes forward may eventually speed the delivery of cell therapies for a broad range of unmet clinical needs."

The study was backed solely by private funding and followed ethical guidelines adopted by the American Society for Reproductive Medicine and the International Society for Stem Cell Research.

The research was done in the New York Stem Cell Foundation Laboratory in New York in collaboration with doctors and researchers at Columbia University Medical Center, whose institutional review board and stem cell committees reviewed and approved the study protocols.

Seeking superior stem cells
Researchers from the Wellcome Trust Sanger Institute announce a new technique to reprogram human cells into stem cells. Their process increases the efficiency of reprogramming by 100-fold and generates cells of a higher quality at a faster rate. By adding two protein factors to the current mix of four, Liu and coworkers brought about dramatic improvement in the efficiency of reprogramming and the robustness of stem cell development.


Sept

"Application of stem cells must be driven by firm evidence"
Ramya Kannan
It is imperative that any application of stem cells in people is driven by firm scientific evidence. Any activity without such evidence must be strictly condoned and prevented, says Sanjeev Gupta, who holds the Eleazar and Feige Reicher Chair in Translational Medicine, Albert Einstein College of Medicine, US.


Aug
Efficient Differentiation of Embryonic Stem Cells into Hepatic Cells In Vitro Using a Feeder-Free Basement Membrane
Substratum

July 2011;
Use of hepatocyte and stem cells for treatment of post-resectional liver failure: are we there yet?
Post-operative liver failure following extensive resections for liver tumours is a rare but significant complication. The only effective treatment is liver transplantation (LT); however, there is a debate about its use given the high mortality compared with the outcomes of LT for chronic liver diseases. Cell therapy has emerged as a possible alternative to LT especially as endogenous hepatocyte proliferation is likely inhibited in the setting of prior chemo/radiotherapy. Both hepatocyte and stem cell transplantations have shown promising results in the experimental setting; however, there are few reports on their clinical application. This review identifies the potential stem cell sources in the body, and highlights the triggering factors that lead to their mobilization and integration in liver regeneration following major liver resections... Continue On To Full Text

Paul Knoepfler at UC Davis
New Podcast; Listen Here

From The Knoepfler Lab Stem Cell Blog  
.
5 Topics
–Stem Cell Tourism in the U.S.
–CIRM
–Article in the Hill by stem cell opponent
–Stem cell hype on aging
..

June 2011;
Nature has an article written by Heidi Ledford discussing the worldwide rapid increase of stem-cell clinics and the dangers of these unproven treatments.

Scope has a nice write up on the article by Eva Valenti, she writes;

Regenerative medicine such as stem cell therapy has cast a ray of hope into many patients’ lives. Stem cell clinics, however, do not always offer patients the most effective treatments. According to a recent Nature article: Many of the treatments such clinics offer — injecting a patient’s own stem cells back into his or her body in a bid to treat conditions ranging from Parkinson’s disease to spinal-cord injuries — are at best a waste of money, and at worst dangerous. “There’s real potential to damage the legitimacy of the field,” says Timothy Caulfield, who studies health law and policy at the University of Alberta in Edmonton, Canada.The potential danger of these clinics is clear: In May, Europe’s largest stem-cell clinic was shut down after its treatments were linked to a child’s death....Please do go read the more at Scope and the original article from Nature.

Related ; Stem Cells; Searching For A Cure " When It Becomes Dangerous"

May 2011

Adult Stem Cells Take Root In Livers And Repair Damage
Ma7 11 2011
Johns Hopkins researchers have demonstrated that human liver cells derived from adult cells coaxed into an embryonic state can engraft and begin regenerating liver tissue in mice with chronic liver damage.
The work, published in the May 11 issue of the journal Science Translational Medicine, suggests that liver cells derived from so-called "induced-pluripotent stem cells (iPSCs)" could one day be used as an alternative to liver transplant in patients with serious liver diseases, bypassing long waiting lists for organs and concerns about immune system rejection of donated tissue.
"Our findings provide a foundation for producing functional liver cells for patients who suffer liver diseases and are in need of transplantation," says Yoon-Young Jang, M.D., Ph.D., assistant professor of oncology at the Johns Hopkins Kimmel Cancer Center. "iPSC-derived liver cells not only can be generated in large amounts, but also can be tailored to each patient, preventing immune-rejection problems associated with liver transplants from unmatched donors or embryonic stem cells." iPSCs are made from adult cells that have been genetically reprogrammed to revert to an embryonic stem cell-like state, with the ability to transform into different cell types. Human iPSCs can be generated from various tissues, including skin, blood and liver cells.

Although the liver can regenerate in the body, end-stage liver failure caused by diseases like cirrhosis and cancers eventually destroy the liver's regenerative ability, Jang says. Currently, the only option for those patients is to receive a liver organ or liver cell transplant, a supply problem given the severe shortage of donor liver tissue for transplantation. In addition, mature liver cells and adult liver stem cells are difficult to isolate or grow in the laboratory, she says. By contrast, iPSCs can be made from a tiny amount of many kinds of tissue; and the embryonic stem-like iPSCs can grow in laboratory cultures indefinitely.
For the study, Jang and colleagues generated human iPSCs from a variety of adult human cells, including liver cells, fibroblasts (connective tissue cells), bone marrow stem cells and skin cells. They found that though the iPSCs overall were molecularly similar to each other and to embryonic stem cells, they retained a distinct molecular "signature" inherited from the cell of origin.

Next, they chemically induced the iPSCs to differentiate first into immature and then more mature liver cell types. Regardless of their origin, the different iPSC lines all showed the same ability to develop into liver cells.

Using mice with humanlike liver cirrhosis, the researchers then injected the animals with either 2 million human iPSC-derived liver cells or with normal human liver cells. They discovered that the iPSC-derived liver cells engrafted to the mouse liver with an efficiency of eight to 15 percent, a rate similar to the engraftment rate for adult human liver cells at 11 percent.

Researchers also found the engrafted iPSCs worked well. The scientists detected proteins normally secreted by adult human liver cells, including albumin, alpha-1-antitrypsin, transferrin and fibrinogen, in the blood of mice transplanted with human iPSC-derived liver cells.

Additional studies will need to be completed before clinical trials can begin, Jang says. One concern has been the potential for embryonic stem cells or iPSCs to cause tumors, though no tumors formed in any of the transplanted mice during the seven months they were studied (equating to more than 30 years in a human life). The scientists also plan to evaluate the impact of molecular memory that may linger in iPSCs for other type of cellular fate changes.

Source: Johns Hopkins Medicine

Contact: Emmanuel Barraud
emmanuel.barraud@epfl.ch
41-216-932-190
Ecole Polytechnique Fédérale de Lausanne


Feb 21 2011

Reprogrammed stem cells hit a roadblock
An international study shows that reprogramming cells leads to genomic aberrations It's a discordant note in the symphony of good news that usually accompanies stem cell research announcements. Stem cells hold enormous promise in regenerative medicine, thanks to their ability to regenerate diseased or damaged tissues. They have made it possible to markedly improve the effectiveness of many medical treatments – muscle regeneration in cases of dystrophy, skin grafts for treating burn victims, and the treatment of leukemia via bone marrow transplants.

The problem is obtaining them. Those that are the true source of life, in the first days of embryonic development, are of course the most highly sought after; still undifferentiated, they are "pluripotent," meaning they can evolve into liver, muscle, eye – any kind of cell. But the issue of how to obtain them clearly raises insurmountable ethical questions.

"In this regard, the recent discovery of the "reprogramming" phenomenon, by which somatic cells can be induced to convert to a pluripotent state simply by forcing the expression of a few genes, opens a phenomenal number of possibilities in regenerative medicine," says Didier Trono, Dean of the EPFL School of Life Sciences. "Imagine, for example, collecting a few cells from the hair follicle of a hemophiliac patient, reprogramming them to the pluripotentiality of their embryonic precursor, correcting the mutation responsible for the coagulation disorder that plagues the patient, and then re-administering them, genetically "cured," after having orchestrated a differentiation into fully functional progeny."

Increased risks for cancer?

But a study that has just been published in the journal Cell Death and Differentiation, to be followed by two articles in the journal Nature, is dampening those hopes. Conducted by the Department of Biochemistry at the University of Geneva and the European Institute of Oncology in Milan, with the participation of Trono's laboratory, it concludes that these reprogrammed cells exhibit a "genomic instability" that appears to be caused by the process used to return the cells to their embryonic state. Even more serious, the genetic mutations observed resemble mutations that are found in cancer cells. The scientists draw the conclusion that reprogrammed stem cells need to be extensively investigated before they can even be considered for use in regenerative medicine.

The experiments were done using mouse mammary and fibroblast cells. The researchers used three different processes for reprogramming the cells to a "stem," or embryonic, state. The first method was developed expressly for this study, and the others have already been well documented.

Yet all the processes led to the same, implacable conclusion: the genetic anomalies multiplied, in a manner that seems to indicate that they are inherent to the reprogramming process itself, which typically makes use of oncogenes. "Interestingly, oncogenes have the potential to induce genomic instability," the authors explain.

These results underline the necessity of conducting further studies. First, to see if the genetic anomalies are serious enough to compromise the function and stability of cells regenerated using the reprogrammed cells; and second, to "refine the methods used for generating induced pluripotent cells, in order to avoid this problem. These results will thus motivate scientists to come up with a solution," concludes Trono.