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Researchers turn living cells into insulin-makers
Wed Aug 27, 2008 1:36pm EDT

By Maggie Fox, Health and Science Editor

WASHINGTON (Reuters) - Researchers have transformed ordinary cells into 
insulin-producing cells in a living mouse, improving symptoms of diabetes in a 
major step towards regenerative medicine.

The technique, called direct reprogramming, bypasses the need for stem cells -- 
the body's master cells which, until now, have been indispensable to efforts to 
custom-make tissue and organ transplants.

The researchers used three genes carried by an ordinary virus to transform 
mouse exocrine cells, which make up about 95 percent of the pancreas, into the 
scarce insulin-producing beta cells that are destroyed in type 1 or juvenile 
diabetes.

In theory, the same is possible using abundant human cells such as liver, skin 
or fat cells, Dr. Douglas Melton and colleagues at Harvard Medical School and 
Children's Hospital in Boston reported.

"It was easier than one might have thought," Melton, a Howard Hughes Medical 
Institute researcher and one of the world's top stem cell experts, said in a 
telephone interview.

"These cells are very stable and live for the life of the mouse."

Scientists had been counting on stem cells to show them how to regenerate 
tissues and organs -- in the case of juvenile diabetes, to regenerate the 
pancreatic cells that are mistakenly destroyed by the body's immune system.

"I wake up every day thinking about how to make beta cells," said Melton, whose 
two children have type 1 diabetes.

The most malleable and promising stem cells have been embryonic stem cells, 
taken from days-old embryos. But U.S. federal law strictly limits funding for 
such research and they are not easy to create.

CELL REPROGRAMMING

Last year, researchers discovered how to reprogram ordinary skin cells by 
taking them back to an embryonic-like state. These induced pluripotent stem 
cells can be used to study disease and might one day make tailor-made 
transplants.

But now Melton and his team -- using knowledge gained from these earlier 
studies -- have skipped both steps.

"What this shows is that you can go directly from one type of adult cell to 
another, without going back to the beginning," said Melton.

Reporting in the journal Nature, the team said they did it in living mice, not 
in lab dishes.

They worked with diabetic mice that do not have the insulin-producing cells 
needed by the pancreas to help the body turn food into energy.

Melton's team had to find which genes were needed to make cells function as the 
precious beta-cells. While every cell carries the full genetic code, only 
certain genes in any cell are working at any given time.

The researchers had to find out which genes are "on" as an embryo grows its 
pancreas.

Out of more than 1,000 genes, they found just three were needed -- Ngn3, Pdx1, 
and Mafa. Then an ordinary cold virus called an adenovirus carried these three 
genes into the digestive-juice-making exocrine cells of the pancreas.

This converted about 20 percent of the exocrine cells to beta cells that 
produced insulin, in turn lowering the soaring blood sugar levels in the mice.

The method might work first in people with severe type 2 diabetes, whose bodies 
no longer make insulin, Melton said.

"For type 1 diabetes we are still faced with the annoying problem of autoimmune 
attack," he said.

Any transformed cells in type 1 diabetes would be destroyed by the same 
mistaken immune response that caused the disease in the first place.

Before experiments begin in people, Melton wants to find a way to transform 
cells without using a virus. Using viruses to treat people, he noted, is risky 
and makes Food and Drug Administration experts nervous.

(Editing by John O'Callaghan)

© Thomson Reuters 2008. All rights reserved. Users may download and print 
extracts of content from this website for their own personal and non-commercial 
use only. Republication or redistribution of Thomson Reuters content, including 
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consent of Thomson Reuters. Thomson Reuters and its logo are registered 
trademarks or trademarks of the Thomson Reuters group of companies around the 
world.
Thomson Reuters journalists are subject to an Editorial Handbook which requires 
fair presentation and disclosure of relevant interests.


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