Transformation of ordinary cells into insulin-makers improves symptoms of diabetes

Aug 28 2008

Scientists in the U.S. have successfully transformed ordinary cells into insulin-producing cells in a living mouse and thereby improved the symptoms of diabetes.

The team from Harvard Medical School and the Children's Hospital in Boston say the research represents a major step towards regenerative medicine.

By using a technique called direct reprogramming the scientists have been able to bypass the need for stem cells.

Stem cells are the body's master cells which have in the past been essential in efforts to grow custom-made tissue and organ transplants.

In the reprogramming process the researchers used three genes carried by an ordinary virus to transform mouse exocrine cells.

Exocrine cells make up almost 95 percent of the pancreas, and the process changed them into the far less common insulin-producing beta cells that are destroyed in type 1 or juvenile diabetes.

Lead researcher Dr. Douglas Melton says in theory the same should be possible by using abundant human cells such as liver, skin or fat cells.

Dr. Melton who is a top stem cell expert says the process was easier than first thought as the cells used are very stable and live for the duration of the life of the mouse.

Until now scientists have relied on stem cells to regenerate tissues and organs and in the case of juvenile diabetes, to regenerate the pancreatic cells that are destroyed by the body's immune system.

The cells with the most promise are embryonic stem cells, taken from days-old embryos, but U.S. federal law has place tight limits on funding for such research and the cells are difficult to create.

In 2007 scientists discovered how to reprogram ordinary skin cells by taking them back to an embryonic-like state and these induced pluripotent stem cells are able to be used to study disease and might in the future make tailor-made transplants a reality.

But Melton and his team have gone directly from one type of adult cell to another, and skipped two steps in the process.

Also interesting is that the research was carried out with live mice bred to have a lack of the insulin-producing cells needed by the pancreas to help the body turn food into energy.

The researchers had to uncover out of more than 1,000 genes, which genes are "on" as an embryo grows its pancreas and they found that just three were needed - Ngn3, Pdx1, and Mafa.

By means of the common cold virus called an adenovirus, the three genes were carried into the exocrine cells of the pancreas, which in turn converted about 20 percent of the exocrine cells into beta cells that produced insulin, lowering the soaring blood sugar levels in the mice.

Dr. Melton says the same method might work in people with severe type 2 diabetes, whose bodies no longer make insulin, but in type 1 diabetes, the problem of autoimmune attack remains and transformed cells would be destroyed by the same mistaken immune response.

The next step say the team, will be to find a way to transform cells without using a virus as using viruses to treat people, is risky.

The research is published in the journal Nature.