Scientists Turn Human Skin Cells Into Stem Cells

TUESDAY Nov. 20, 2007 -- Two separate groups of scientists have succeeded in turning human skin cells into cells that are very similar -- but not identical -- to embryonic stem cells.

The two teams, one based in Japan and the other in Wisconsin, used slightly different methods to achieve essentially identical goals, researchers said.

"Embryonic stem cells can divide forever, and there has never been good evidence for such cells in adults, but this new paper shows a method to make cells essentially identical to embryonic stem cells," said James Thomson, senior author of the Wisconsin study and a professor in the departments of medicine and public health at the University of Wisconsin-Madison. "This will change the ethical debate," he said at a teleconference held Tuesday.

"We are now in a position to be able to generate patient- and disease-specific stem cells, without using human eggs or embryos," added Dr. Shinya Yamanaka, senior author of the first paper, who is affiliated with Kyoto University in Japan and the Gladstone Institute of Cardiovascular Disease in San Francisco. "These cells should be useful in understanding disease mechanisms, searching for effective and safe drugs, and treating patients with cell therapy," he said.

One outside exert agreed the achievement could shift research away from embryonic stem cells.

"Here's verification of another source of multipotent cells that could be useful for treating disease and would get around some of the ethical issues related to embryonic sources," Paul Sanberg, distinguished professor of neurosurgery and director of the University of South Florida Center for Aging and Brain Repair in Tampa, told HealthDay. "It also demonstrates that there are many cells that can be reprogrammed in the body, and this is not going to be the last time we hear of other types of cells and other ways we can make multipotent."

Multipotency or pluripotency refers to the ability of stem cells to grow into a variety of cell types.

However, the journey from laboratory to patient therapy is still a long one, experts said.

"This is a proof of principle, but, in terms of application, there are many steps in between," said Dr. Robert Tsai, assistant professor in the Center for Cancer and Stem Cell Biology at Texas A&M Health Science Center Institute of Biosciences and Technology in Houston.

The achievements followed closely on the heels of another breakthrough: Last week, U.S. scientists announced that they had created dozens of cloned embryos from a 10-year-old male macaque, a primate. This puts science one step closer to human cloning, those authors stated.

Embryonic stem cells are pluripotent, meaning they have the ability to develop into virtually any cell type in the body. The hope is that such cells may one day yield treatments or cures for diseases such as diabetes, liver failure, spinal injury, stroke, Alzheimer's disease and heart disease.

However, harvesting embryonic stem cells involves destroying a viable embryo, stirring much political debate. In the United States, embryonic stem cell research has been severely limited since August 2001, when President George W. Bush placed limits on federal funding of the field and restricted the number of embryonic stem cell lines that could be used.

Since that time, researchers have been racing to find other sources of viable stem cells. The approach documented in these two studies would circumvent the need for embryos and, thus, would bypass any controversy. The findings of Yamanaka's team are detailed in the Nov. 30 print issue of Cell, and the Wisconsin group's work was released online Tuesday by Science.

Last year, Yamanaka's team transformed mouse skin cells into pluripotent stem cells.

This year, the researchers tried the same method in humans: using a retrovirus to activate specific transcription genes in the skin cells. Transcription genes regulate gene expression, explained Yamanaka.

Using this method, his group generated about 10 cell clones from 50,000 human facial skin cells.

The new "induced pluripotent stem" (iPS) cells were identical to embryonic stem cells in terms of appearance and behavior in cell culture. They also expressed genetic markers that were the same as those observed in embryonic stem cells.

The iPS cells could also differentiate into other tissue types, the team found.

However, a screen of more than 30,000 genes showed that the iPS cells were not actually indistinguishable from embryonic stem cells. In fact, roughly 1,000 genes were expressed differently.

"Human iPS cells are similar, but not identical, to human embryonic stem cells, Yamanaka said. "DNA microarray analyses identified differentially expressed genes between the two stem cell lines. Further studies are required to determine whether human iPS cells can replace human ES cells."

The team at the University of Wisconsin-Madison also used human skin cells, then added two of the same genes as Yamanaka's team and two different genes in their approach. The outcome was essentially the same.

"The actual combination of the factors they put in are different, the rationale is the same," Tsai explained. "There are some tiny differences between the two different combinations."

The advent of the new cells does not render embryonic stem cells unnecessary, however.

"This does not mean that it is the end of embryonic stem cell research, if only that we need a gold standard to compare to," the University of Wisconsin's Thomson told reporters. "Over time, I believe embryonic stem cells will be used by fewer and fewer labs. These new stem cells would not have been derived if it had not been for the last 10 years of research on embryonic stem cell lines. I do, nonetheless, think that the world has changed."

Can the newly designed cells be used to clone humans? "Any cell in the body can do that," Thomson said. "It's probably true of these cells, if you manipulate them enough, but not if you put them in the body as they are."

It's not clear in either of the two new studies if the cells are completely pluripotent or if one line is more efficient than the other. "Will they have the ability to fully differentiate?" Tsai asked. "There's some evidence that they can move from a differentiated state to an undifferentiated state, but will they be able to reverse back?"

"We have to be sure the cells are safe," Yamanaka said. "One of the difficulties about human embryonic stem cells is their tumorigenicity [propensity to develop tumors]. Because of the usage of retroviruses, iPS cells may be more tumorigenic than human embryonic stem cells. We will have to find a way to avoid retroviruses."

But for the more immediate purposes of drug discovery and toxicology, the use of retroviruses is not a big problem, Yamanaka added.

iPS may present their own ethical concerns, however, if they are used to generate sperm and egg cells. "This might help people with infertility problems, but it will be essential to have proper regulation regarding the generation and usage of human iPS cells to avoid misusages of this technology," Yamanaka said.

More information

Learn more about stem cells at the International Society for Stem Cell Research.

Posted: November 2007


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