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Transplanted pancreatic stem cells can reverse diabetes in mice

Abi Berger , BMJ

People with diabetes could one day undergo transplantation of pancreatic stem cells to provide them with a permanent source of insulin, according to a study in Nature Medicine (2000;6:278-82).

Ammon Peck, professor of pathology and laboratory medicine at the University of Florida, and his colleagues have successfully cultured pancreatic stem cells harvested from mice, transplanted them back into diabetic mice, and then shown that the diabetic state was reversed.

The researchers, together with a team from Ixion Biotechnology, harvested pluripotential ductal structures from adult non-obese diabetic mice (NOD mice) that had not yet developed diabetes; pancreatic stem cells were extracted from these structures. The extracted tissue was then grown in culture, and cells were obtained that had, over several months, differentiated into mature, fully functioning islets of Langerhans, capable of producing insulin.

To confirm that the cells worked appropriately, the researchers added increasing concentrations of nicotinamide (which stimulates insulin secretion) and glucose, and the cells produced insulin in response to this challenge.

The next stage was to find out if the cultured cells could reverse diabetes. "We took a sample of differentiated cells and transplanted them just below the kidney capsule in frankly diabetic female NOD mice," explained Desmond Schatz, one of the team. "Despite being subsequently weaned off their insulin injections, these mice remained healthy," he said.

The transplant recipient mice were killed at various stages, but throughout the observation period, which lasted 55 days, the team found that the transplanted cells continued to secrete insulin.

The control mice, which had not received transplanted pancreatic cells, died rapidly after the insulin injections were stopped. "Our preliminary experiments show that transplantations of pancreatic islet cells, derived from stem cells, are capable of reversing diabetes in NOD mice," said Dr Schatz.

The team is now investigating whether similar results can be achieved using cells derived from pancreatic tissue taken from human cadavers. Early results suggest that ductal tissue taken from human cadavers can be grown in culture to form functioning islet cells.

Such a source of tissue, said Dr Schatz, could prove better than relying on fetal tissue, and may even lead eventually to autologous pancreatic transplants. "It might be possible to harvest pancreatic tissue from diabetic patients who still have some surviving functioning islet cells, grow them up, and then transplant them back," he said.

This would not only avoid some of the risks associated with the rejection of foreign tissue but could also potentially end the need for daily injections of insulin.