Pluripotent stem cells and diabetes : basic science to clinical applications

Type 1 diabetes is caused by the loss of insulin-producing (β) cells in pancreas. A significant advance in cell therapy for diabetes has been the development of a protocol for islet transplantation from Dr. James Shapiro and colleagues at the University of Alberta in Edmonton, Canada (the Edmonton protocol). However, lack of suitable organ donors for transplantation is a critical factor that limits this therapy from majority of individuals suffering from diabetes. Research in the last decade has therefore been largely focused on generating insulin-producing cells that can be easily obtained (derived) and used in transplantation setting for replacement therapy in diabetes. Although insulinproducing cells have been obtained from various sources including human ES cells, bone marrowderived mesenchymal cells, umbilical cord-blood derived mesenchymal cells, transdifferentiation of liver / gallbladder cells, pancreatic duct cells, exocrine cells as well as islet-derived mesenchymal cells, the amount of insulin produced by most of these cell types is significantly less as compared to the amount of insulin produced by a normal adult pancreas. Present research is therefore focused on understanding signalling molecules and processes that would enhance differentiation of these cells. Although embryonic pluripotent/stem cells may be limited due to ethical issues, adult tissue-derived progenitor cells are believed to possess inherent traits that result in "commitment" to a particular phenotype, demonstrated by their relatively restricted differentiation capacity. In this chapter, we discuss the cell types that have been studied for replacement therapy in diabetes with specific reference to their possibility for use in a clinical setting.