Efficient differentiation of insulin-producing cells from skin-derived stem cells

Type 1 diabetes mellitus, characterized by loss of pancreatic beta-cells, can be ameliorated by islet transplantation, but this treatment is restricted by the scarcity of islet tissue and by allograft rejection. We isolated and characterized skin-derived precursors (SKPs) - an abundant source of autologous cells - and developed an experimental strategy to convert them into insulin-producing cells (IPCs) in vitro within a short period of time, through extracellular factor modification and analyses of IPCs by reverse transcription-polymerase chain reaction, immunocytochemistry and enzyme-linked immunosorbent assay. SKPs could self-assemble to form three-dimensional islet cell-like clusters (dithizone-positive) and co-express insulin and C-peptide. In addition, they expressed multiple genes related to pancreatic beta-cell development and function (e.g. insulin 1, insulin 2, islet-1, Pdx-1, NeuroD/beta2, glut-2 and Nkx6.1), but not other pancreas-specific hormones and enzymes (e.g. glucagon, somatostatin and amylase). Moreover, when stimulated with glucose, these cells synthesized and secreted insulin in a glucose-regulated manner. The findings of this study indicate that SKPs can differentiate into functional IPCs and can provide an abundant source of autologous cells for transplantation. This study also provides strategies to derive autologous islet-replacement tissues from human skin stem cells.