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Diabetes Research Fuels Embryo Stem Cell Debate

Posted on: Thursday, 6 May 2004, 06:00 CDT

The scientific and political tug of war over human embryo research escalated yesterday as new research backed the controversial contention that stem cells from embryos have greater potential to cure diabetes than stem cells from adults.

Several experts, however, said the new work falls far short of settling the debate over the relative merits of the two kinds of cells for medical treatments. Indeed, some said, entirely different approaches may prove curative before any stem cell therapy emerges for diabetes, which affects 16 million Americans.

Harvard cell biologist and study leader Douglas Melton, a vocal proponent of research on embryonic stem cells, said the new experiments, done with mice, undermine previous results that had seemed to show the existence of "adult pancreatic stem cells."

Those studies, also limited to mice, had offered evidence that certain organs in adult animals harbored stem cells that could transform themselves into insulin-producing "beta cells," which are missing or not working in diabetics. If similar cells exist in human adults, some proposed, perhaps they could be coaxed in laboratory dishes to become beta cells for transplantation into diabetics.

But the new study, Melton said, "provides no evidence whatsoever for the existence of an adult pancreatic stem cell."

The findings feed into a highly politicized battle over the existence and relative therapeutic potential of various kinds of stem cells -- self-replenishing cells that can morph into other kinds of body cells.

The 1998 discovery of human embryonic stem cells, which develop within five-day-old embryos and can turn into every known kind of human tissue -- sparked a revolution in cell biology as researchers imagined using them to repair or regenerate ailing organs. But that revolution has been tempered by ethical concerns -- human embryos must be destroyed to retrieve the cells -- and by more recent revelations that other kinds of stem cells exist in adult organs and may have similar medical potential.

For diabetes researchers, the question has been whether embryonic stem cells are the only ones capable of turning into new insulin-secreting beta cells, which in about 10 percent of diabetics are destroyed by a malfunctioning immune system and in others fail for other reasons.

Previous mouse studies had offered evidence that certain cells in the adult pancreas, spleen and bone marrow can make that transformation. In one study, diabetic mice no longer needed insulin shots after getting transplants of adult pancreatic cells that tests had indicated might be adult stem cells.

In the new work, Melton used highly sophisticated genetic tracking systems to see where new beta cells come from in normal mice during recovery from surgical trauma to their pancreas. New beta cells, he showed, came only from older beta cells undergoing cell division -- not from any other kind of cell, such as a stem cell, transforming itself into beta cells.

The results highlight that "embryonic stem cells are currently the only type of stem cell that is unquestionably capable of differentiation into beta cells," Melton's team concludes in today's issue of Nature.

"It's a tightly done experiment and the results are clear," said Ronald McKay, a stem cell researcher at the National Institute of Neurological Disorders and Stroke.

But others said the experiments, which involved healthy mice, were of questionable relevance to humans (or mice) with diabetes, whose pancreases operate abnormally under the stress of disease.

"To see the effect of stem cells [making beta cells] you may need a more realistic situation like diabetes," said stem cell researcher Vijay Ramiya of the University of Florida.

Harvard researcher Denise Faustman, who has published evidence adult cells can become beta cells in diabetic mice, said the new work supports her belief the pancreas can regenerate itself in many ways.

"Now the debate is not whether it can happen but how many ways does it happen, and this is a good problem to have," Faustman said.

It may be, she and others said, that the best way to make more beta cells will not involve stem cells at all, but will use drugs that encourage beta cells to make many more of themselves, as they did in Melton's tests. Melton said he does not think beta cells can divide enough times to constitute a cure.

Even if scientists find a way to replace disappearing beta cells in diabetics, experts agreed, it will be for naught if no way is found to block the immune system reaction that destroys their insulin-producing cells.

Reported By TechNews.com, http://www.TechNews.com

(20040506/WIRES /)

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