Neogenesis of pancreatic endocrine cells in copper-deprived rat models.

Transplantation of progenitor cells for regeneration of islet cells could prove invaluable in the treatment of diabetes mellitus. This study provides evidence that in rats maintained on a copper-deficient diet containing the copper-chelating agent tetraethylenepentamine pentahydrochloride, regeneration of single alpha and beta endocrine cells in the ductules and acinar tissue of the adult rat pancreata occurred. These regenerated cells both in the ductules and acinar tissue stained positive for glucagon and insulin similar to cells within the islets and in addition to being reactive to proliferative cellular nuclear antigen, an intracellular marker of active proliferation. In contrast, the control group pancreata did not show any evidence of islet regeneration, proliferation, or proliferative cellular nuclear antigen reactivity pre- or posttransplantation. Transplantation of digested pancreatic tissues from the copper-deficient group into the spleen of syngeneic diabetic rats reversed diabetes, and this was confirmed histologically by demonstrating cells within ductules that stained positively for insulin. This study concludes that copper deprivation contributes to the neogenesis of pancreatic alpha and beta cells in the ductules and acinar tissue of adult pancreas in rat model and that transplanted stem cells maintain their functional capacity in the recipient after transplantation.