Rat-grown, genetically matched pancreases reverse diabetes in mice

Stanford University and University of Tokyo researchers transplanted mouse pancreatic cells, grown in rats, into diabetic mice. The method reversed the mice’s disease and could lead to a similar approach in humans with diabetes.

The scientists implanted mouse pluripotent stem cells into rat embryos that were genetically modified so they would not develop their own pancreases. They grew the pancreases in rats so that the organs would be large enough and contain enough insulin-producing cells to reverse diabetes in mice.

Then they transplanted 100 islets—groups of insulin-secreting pancreatic cells—into mice with drug-induced diabetes. Because the transplanted cells contained some stray rat cells, the mice were given immunosuppressive drugs for five days after transplant. But they didn’t need lifelong immunosuppression because each mouse received islets that were a genetic match.

At the 10-month mark, the team removed the islets from some mice.

"We examined them closely for the presence of any rat cells, but we found that the mouse's immune system had eliminated them," said Dr. Hiromitsu Nakauchi, a professor of genetics at Stanford. "This is very promising for our hope to transplant human organs grown in animals because it suggests that any contaminating animal cells could be eliminated by the patient's immune system after transplant."

If it proves possible to grow human organs in large animals, this method, which the researchers reported in Nature, could represent a new treatment for diabetes. Scientists have already shown that transplanting functional islets from healthy pancreases is a viable option to treat diabetes in humans, provided rejection can be avoided, the scientists said in the statement.

The Stanford technique could also lead to the growth of genetically matched human organs other than pancreases in large animals, which could put a dent in the shortage of donor organs and eliminate the need for lifelong immunosuppression by transplant recipients.

The fight against diabetes has included many different approaches for replacing the insulin-secreting role of the pancreas. For example, Medtronic’s MiniMed 670G is often called an “artificial pancreas,” because it comprises a glucose sensor, insulin pump and infusion patch. It’s officially a “hybrid closed-loop system” that regulates basal insulin. But it still requires patients to manually deliver bolus insulin after meals.

That's why research teams across the world are still looking for more effective ways to restore the body's own insulin production. The Stanford team admits that while their work is promising, they'll have to carefully consider the ethics behind transplanting human cells into animals. They continue their research, however, and are currently working on animal-to-animal transplants of kidneys, livers and lungs.