Cell transplants combat diabetes in mice

By providing ailing mice with cells grown from the pancreatic tissue of genetically identical healthy animals, scientists have reversed a mouse version of diabetes, according to a new study. Their findings suggest a new route for treatment of diabetic patients.

Although tissue or organ transplants would seem to present an ideal weapon against diabetes, this approach had been disappointing. Transplants of pancreatic tissue had poor success rates in people, says study coauthor Ammon B. Peck of the University of Florida College of Medicine in Gainesville.

If transplant surgery was to succeed, the diabetes patient would be swapping a life-long regimen of insulin for immune-suppressant drugs that keep the body from rejecting the new tissues. In rare cases where patients could be weaned from immune suppressors, there would remain the nagging concern that the autoimmune onslaught that killed off the person’s original insulin-producing cells could reawaken and destroy the transplanted cells.

No autoimmune backlash occurred in the mouse study. Peck and his colleagues worked with mice that have a disease that simulates juvenile onset, or type I, diabetes. They obtained cells from mice that had not yet shown symptoms.

The insulin-producing beta cells of the pancreas normally grow in clusters called islets of Langerhans. The team derived islet stem cells from ducts of a mouse pancreas and then grew the cells in culture before transplanting them into a kidney of a genetically identical diabetic mouse.

Using identical mice avoided the transplant-rejection problem, but the researchers say they don’t know why the mouse immune systems didn’t attack these reimplanted cells as they had the original islets.

These new islet cells were still somewhat immature, Peck says, and when grown in the laboratory, they don’t produce much insulin when they encounter glucose. The study doesn’t elucidate how such poor insulin producers can reverse diabetes in the mice, says Lawrence Rosenberg of McGill University Health Centre in Montreal.

Peck says these cells may see a boost in their insulin-producing capabilities when placed in a living mouse. In his experiment, eight untreated diabetic mice taken off insulin injections reverted to diabetes and died, whereas eight diabetic mice getting transplants remained healthy when taken off insulin.

The new islet cells reformed into clusters and grew in the kidneys, he says. Also, in two out of three other mice, a web of essential tiny blood vessels grew around islet cells transplanted under the skin, the researchers report in the March Nature Medicine.

Still, to prove that the transplants caused the diabetes reversal, the researchers need to remove islets from the mice hosting transplants to see whether they then revert to diabetes, says Henry Lau of Johns Hopkins Medical Institutions in Baltimore.

Despite the lingering questions, the study “is tremendous,” says Bernhard J. Hering of the University of Minnesota in Minneapolis. “The whole field of islet-cell transplants is about to explode.”