Researchers Transform Ordinary Cells Into Insulin-Producing Cells In Living Mouse

In a technique called direct reprogramming, researchers have changed ordinary mouse pancreas tissue into insulin producing cells. Considered as a major step towards regenerative medicine, this technique undermines the importance of stem cells which are the body’s master cells and have been indispensable to try to make-to-order tissue and organ transplants.

The study led by Qiao Zhou of the Harvard Stem Cell Institute opens the door for treatments for diabetes, as well as heart and brain ailments. Three genes carried by an ordinary virus were used to transform mouse exocrine cells into the insulin providing beta cells that are destroyed in type 1 or juvenile diabetes. The exocrine cells make up about 95 % of the pancreas and in juvenile diabetes and some adult diabetes or type 2 diabetes; patients suffer from a lack of beta cells. If ordinary pancreas cells could be changed into beta cells not only would it make treatment possible for these patients, a similar approach might be able to make replacement heart or brain tissue. Doctors would though still need to work on preventing the patient’s immune system from mistakenly destroying the new cells like they destroyed the original ones.  

Dr. Douglas Melton and colleagues at Harvard Medical School and Children's Hospital in Boston said, "It was easier than one might have thought. We 'flipped' the cells from one state to another.” He said theoretically it was possible to get the same results using abundant human cells such as liver, skin or fat cells and scientists have long hoped that stem cells would show them the way to regenerate tissues and organs.

Melton, a Howard Hughes Medical Institute researcher and one of the top stem cell experts, further added, "These cells are very stable and live for the life of the mouse."
Cell biologist Alex Meissner of the Broad Institute in Cambridge, Mass. called the study "a very elegant and important contribution to the reprogramming field," and said "It would indeed be very nice if we could convert any one cell type into a different one."

The most promising stem cells have been embryonic stem cells taken from just days old embryos. These are the master cells from which specialized tissue comes but it is controversial and U.S. law limits funding for such research as harvesting these involves destruction of embryos.

In earlier studies done researchers had discovered how to reprogram ordinary skin cells by taking them back to an embryonic stage. Melton and his team have used earlier studies to give them a basis but have skipped both the steps and they used living mice not lab dishes. "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 worked with diabetic mice that did not have the insulin producing cells needed by the pancreas to convert food into energy. Melton felt the method might work for people who had severe type 2 diabetes and whose bodies don’t make insulin. "For type 1 diabetes we are still faced with the annoying problem of autoimmune attack," he said.

In type 1 diabetes any transformed cells would be destroyed under the same mistaken immune response that destroyed the original cells and caused the disease. Melton, whose two children have type 1 diabetes says, "I wake up every day thinking about how to make beta cells." He however warns that treatments with these reprogrammed cells have to first be tested in human cells, and before that a way to transform these cells without using a virus is needed. Using viruses can be risky and this might take years.