[Adult stem cells regenerate the endocrine pankreas and normalize hyperglycaemia and insulin production in diabetic mice].

Aims: The potential role of adult stem cells in the regeneration of beta cells in diabetes is still controversial. Although islet cell transplantation is currently the most pursued field of research, we have investigated the capacity of multipotent adult stem cells to correct hyperglycaemia in an experimental murine diabetes model.

Methods: Cloned stem cells were labelled with eGFP or transfected with a pTie2-RFP construct to show endothelial differentiation in vivo. The beta cell toxin alloxan was injected intravenously and all mice became hyperglycaemic (> 400 mg/dl) within two days and lost more than 90 % of their beta cell mass. Stem cells were then injected either directly into the pancreas or given systemically.

Results: Mice that received stem cell transplantation reached normal blood glucose levels within 14 days and the beta cell mass fully recovered within one month after treatment, regaining normal body weight soon after stem cell infusion. The host pancreas then dissociated and further analysed. The eGFP+ donor cells did not express insulin and other endocrine markers, but showed a red fluorescence (RFP+) and CD31 expression instead, characteristics of endothelial cells after pTie2 activation. It was further shown that remaining (eGFP-) beta cells showed increased cell cycle activity.

Conclusions: Endothelial differentiation from transplanted stem cells, induced by the environment of an injured pancreas, allows the regeneration of insulin production either through proliferation of still existing and residual beta cells in the islet or the recruitment and differentiation of beta cell progenitors mostly from the duct region via enhanced vasculogenesis and microcirculation.