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SAM ODGEN VIA THE WHITEHEAD INSTITUTE / AP
Researchers have bred mice that have reprogrammed cells, which could eventually ease transplants.

Toronto Star
Stem cell breakthrough heralded
Researchers were able to create stem cells in mice from adult skin cells, a process considered `ethical'
Jun 07, 2007 04:30 AM
Joseph Hall
health reporter

Scientists have developed a new way to produce embryonic stem cells that could lead to an endless supply of the body's basic building blocks and avoid ethical controversies that have dogged their use in cutting-edge medical research.

Researchers from UCLA and Harvard University say they were able to transform skin cells from adult mice into embryonic stem cells, a process that holds promise for organ and tissue transplantation.

If it could be duplicated in humans, the reprogrammed stem cells – which can grow into any type of tissue in the body – could be used to create individualized replacements for diseased organs and tissues that wouldn't be rejected by the immune system, the paper says.

"It's super exciting," says Kathrin Plath, a biological chemist at UCLA's Institute for Stem Cell Biology and Medicine and a co-author of the study. "It's opened up an entire field of research. There will be so many who will find this interesting who can (work with) it."

The study, published today in the inaugural issue of the peer-reviewed journal Cell Stem Cell, is being heralded as a major discovery in the burgeoning field of stem-cell research.

In the short term, the procedure could provide an ample supply of embryonic stem cells for research into potential life-saving therapies, skirting ethical issues associated with cloning technology or the use of discarded embryos from fertility clinics.

"If this holds up I think it's quite an amazing advance," says Dr. Alan Bernstein, president of the Canadian Institutes of Health Research and one of the country's top stem-cell researchers. "It's a real important piece of work, absolutely."

Plath's team used fully developed mouse "fibroblast" cells, which form the connective tissue of the skin, because they were the easiest cells to access.

In the lab they used a virus to transport four specific "transcription factors" – genes used to switch on or off other genes – directly into the DNA strands within the nuclei of the rodent skin cells.

The transcription factors reprogrammed the skin cells into embryonic stem cells, which were then inserted into mice embryos and went on to develop into cartilage, liver, heart, lung and blood tissues.

Transcription factors are orchestrating genes that direct the rest of the DNA "blueprint" within our cells to create the various tissues and functions in humans.

In the case of the California research, the four transcription factors directed the DNA to create the "pluripotent" embryonic stem cells that can grow into any tissue or organ.

Working from an earlier Japanese study that identified the four transcription factors, the new research also shows they were "indistinguishable" from normal embryonic stem cells in their chromosomal structure.

Plath cautions it might be months or years before they know if it works in human cells and then they would have to determine which ones are best for reprogramming.

But both she and Bernstein say the same four transcription factors that worked in mice should theoretically work in human cells.

The research has the potential to lead to organ or cell generation that could cure illnesses without the risk of immune rejection, a big complication for such patients.

If cells from a transplant patient could be transformed into embryonic stems cells, they might be coaxed to grow into blood, heart or lung tissue, for example.

The process could be used to create immune-proof embryonic stem cells that could be injected directly into ailing organs to repair damage. The use of stem cells to treat Alzheimer's disease, for example, has been anticipated for several years.

Bernstein says there would be few ethical questions arising from the technique, as it would use adult cells to create a stem-cell supply.

Up till now, researchers had to rely on discarded embryos from fertility clinics to get the embryonic stem cells.

In the U.S., the Bush government has denied federal funding to researchers who use them.

And therapeutic cloning – a technique that replaces the DNA of a fertilized human egg with adult cell DNA – has been banned in Canada and other western countries. Although the technique has never been successfully performed with human cells, it requires the creation of embryos and has the potential to lead to a human clone.

http://www.thestar.com/sciencetech/article/222722