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Is there a future for stem cell therapies that don’t use embryonic stem cells? An international study involving EPFL has raised doubts, by showing that “reprogramming” adult stem cells leads to genetic 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.

from http://goo.gl/elaDN

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Discovery sheds new light on the process of stem cell generation, and will help promote safer stem-cell based studies and future clinical trials.

Dr. Andras Nagy’s laboratory at the Samuel Lunenfeld Research Institute of Mount Sinai Hospital and Dr. Timo Otonkoski’s laboratory at Biomedicum Stem Cell Center (University of Helsinki), as well as collaborators in Europe and Canada have identified genetic abnormalities associated with reprogramming adult cells to induced pluripotent stem (iPS) cells. The findings give researchers new insights into the reprogramming process, and will help make future applications of stem cell creation and subsequent use safer. The study was published online today in Nature.

The team showed that the reprogramming process for generating iPS cells (i.e., cells that can then be ‘coaxed’ to become a variety of cell types for use in regenerative medicine) is associated with inherent DNA damage. This damage is detected in the form of genetic rearrangements and ‘copy number variations,’ which are alterations of DNA in which a region of the genome is either deleted or amplified on certain chromosomes. The variability may either be inherited, or caused by de novo mutation.

“Our analysis shows that these genetic changes are a result of the reprogramming process itself, which raises the concern that the resultant cell lines are mutant or defective,” said Dr. Nagy, a Senior Investigator at the Lunenfeld. “These mutations could alter the properties of the stem cells, affecting their applications in studying degenerative conditions and screening for drugs to treat diseases. In the longer term, this discovery has important implications in the use of these cells for replacement therapies in regenerative medicine.”

“Our study also highlights the need for rigorous characterization of generated iPS lines, especially since several groups are currently trying to enhance reprogramming efficiency,” said Dr. Samer Hussein, a McEwen post-doctoral scientist who initiated these studies with Dr. Otonkoski, before completing them with Dr. Nagy. “For example, increasing the efficiency of reprogramming may actually reduce the quality of the cells in the long run, if genomic integrity is not accurately assessed.”

A new research has suggested that cardiac stem cells - even in elderly and sick patients – could generate new heart muscle and vessel tissue and be used to treat heart failure.

Scientists surgically removed tissue from the muscular wall of the heart’s chambers in 21 patients.

They then isolated and multiplied the cardiac stem cells (CSCs) found there.

Most of the patients had ischemic cardiomyopathy (enlarged and weakened muscle due to coronary artery disease). Eleven also had diabetes. The average age of patients was about 65.

“Regardless of the gender or age of the patient, or of diabetes, we were able to isolate in all of them a pool of functional cardiac stem cells that we can potentially use to rescue the decompensated human heart,” said Domenico D’Amario, author of the study and a postdoctoral fellow at the Center for Regenerative Medicine at Harvard, Boston, Mass.

The study has been presented at the American Heart Association‘s Scientific Sessions 2010. (ANI)

“The tracheal team at Great Ormond Street Hospital is delighted that Ciaran is going home after his tracheal transplant. He is a wonderful boy who has become a great friend to us all, and he and his infinitely patient family have charmed us all. Ciaran has become our local iPad expert, and we will miss his advice. His recovery has been complicated, as one might expect for a new procedure, and we have kept him under close surveillance, hence the length of time he has been here. It is wonderful to see him active, smiling and breathing normally. We are very proud of him!

“Ciaran will continue to need regular follow up by us. This is so we can both make sure he is ok, and also learn what to expect for the next patient who needs this innovative therapy. The treatment offers hope to many whose major airways were previously considered untreatable or irreplaceable. We will continue to work with our colleagues in regenerative medicine throughout the world to ensure we can continue to improve both the science and treatment options.”

from http://www.ich.ucl.ac.uk/pressoffice/pressrelease_00852

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Dozens of people who were blinded or otherwise suffered severe eye damage when they were splashed with caustic chemicals had their sight restored with transplants of their own stem cells — a stunning success for the burgeoning cell-therapy field, Italian researchers reported Wednesday.

The treatment worked completely in 82 of 107 eyes and partially in 14 others, with benefits lasting up to a decade so far. One man whose eyes were severely damaged more than 60 years ago now has near-normal vision.

“This is a roaring success,” said ophthalmologist Dr. Ivan Schwab of the University of California, Davis, who had no role in the study — the longest and largest of its kind.

Stem cell transplants offer hope to the thousands of people worldwide every year who suffer chemical burns on their corneas from heavy-duty cleansers or other substances at work or at home.

The approach would not help people with damage to the optic nerve or macular degeneration, which involves the retina. Nor would it work in people who are completely blind in both eyes, because doctors need at least some healthy tissue that they can transplant.

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Chinese researchers have become the world’s fifth most prolific contributors to peer-reviewed scientific literature on Regenerative Medicine (RM), according to an international study published on Friday (…)
Regenerative Medicine is an emerging interdisciplinary field of research and clinical applications focused on the repair, replacement or regeneration of cells, tissues, or organs, which uses a combination of approaches including gene therapy, stem cell transplantation, tissue engineering, and the reprogramming of cell and tissue types.

But as the stem cell research develops fast in recent years, RM becomes more and more dependent on this side, and shared some ethic criticism against stem cell research since it involves the usage of human embryos.