earticle

영어

While subcutaneous tissue has been proposed as an optimal site for pancreatic islet transplantation, concern remains that the microvasculature of subcutaneous tissue is too poor to support transplanted islets. In an effort to overcome this limitation, we evaluated whether fibrin gel with human adipose-derived stem cells (hADSCs) and pancreatic islet cells could cure diabetes mellitus if transplanted into the subcutaneous space of diabetic mice. The fibrin gel with islet cells and hADSCs was subcutaneously implanted into diabetic mice resulting in normalization of the recipient’s blood glucose levels. These results were enhanced by co-treatment of fibroblast growth factor-2 (FGF2) in the fibrin gel. The hADSCs induced formation of new microvasculature via overexpression of vascular endothelial growth factor (VEGF), reducing apoptosis of the co-transplanted islet cells (enhancement of Bcl-2 expression in islets). The new microvasculature was likely secondary to induction by hypoxia-induced factor-1a (HIF-1a) in hADSCs, but may also be derived from recipient endothelial cells. Secondary to insulin contained within the co-transplanted islets, the hADSCs did not directly differentiate into endothelial cells (no detection of biomarkers of human endothelial cells), but instead into insulin-secreting cells (detection of human insulin). Mice receiving islet cell transplantation alone did not become normoglycemic. Collectively, cotransplantation of fibrin gel with islet cells and hADSCs will expand the indications for islet cell transplant therapy and the potential clinical application of cell-based therapy.