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Islet Cell Transplants Cure Diabetes Without Immunosuppression

Jun 22, 2004

A new way to transplant insulin-producing beta cells.

Intraperitoneal transplantation of rudimentary pancreatic cells from rat embryos into adult diabetic rats normalizes glucose levels and does not require immunosuppression, a Washington University School of Medicine research team reports.

Dr. Marc R. Hammerman stated that they followed the animals for about a year and they maintain normal glucose tolerance. That’s about half the life-span of a rat, so this is definitely for keeps.

As they report in the American Society for Artificial Internal Organs Journal for September/October, Dr. Hammerman and colleagues removed pancreatic anlagen from day 12.5 rat embryos, which is within 1 day of organ formation. They implanted the tissue into a fold of peritoneum adjacent to a branch of the superior mesenteric artery.

Two weeks later, the cell had grown and undergone differentiation and stained positive for insulin, the St. Louis-based team indicates. By day 35 after transplantation, transplanted animals’ blood glucose levels had normalized.

Electron microscopy performed at 15 weeks demonstrated beta cells within islets, with cytoplasm "packed with neurosecretory granules containing dense cores that represent crystallized insulin," they write. Glucose tolerance test results of transplanted animals at week 18 did not differ from those of control rats.

"The key to this is to obtain the tissue as early as possible after the pancreatic anlagen form," before the formation of mature antigen-producing cells. At this stage, only the endocrine component grows and differentiates. The exocrine component of the pancreas does not develop.

Since submitting this research, he and his colleagues have refined the procedure and successfully transplanted pancreatic anlagen from pigs into rodents, without needing costimulatory blockade or other immunosuppressive treatments. "The next step is to go from pigs into primates."

Advantages over current treatment with adult kidney-pancreas transplants include unlimited tissue availability and freedom from the requirement for immunosuppressive agents. It is likely to be better than stem cell transplantation, Dr. Hammerman added, because anlagen can differentiate, grow and produce insulin without manipulation of cells in culture or addition of specific growth factors.
ASAIO J 2003;49:00-00.


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