The use of animal models to study stem cell therapies for diabetes mellitus

The two main forms of human diabetes mellitus (DM) are characterized by an absolute (type 1) and a relative (type 2) reduction in functional insulin-producing β cell mass in the pancreas. Type 1 DM results from autoimmune assault of β cells, and type 2 from the failure of pancreatic β cells to sufficiently compensate for insulin resistance. Studies indicate that the incidence of both types is increasing rapidly to levels that constitute a global epidemic. Researchers are experimentally developing several conceptual approaches for increasing pancreatic β cell mass and testing them for feasibility in treating the disease. The main sources for derivation of insulin-producing cells are embryonic and induced pluripotent stem cells, endogenous progenitor cells (both within and outside the pancreas), stimulation of β cell proliferation, and genetic "reprogramming" of cells. Strategies to effectively address immune- and inflammationmediated assault on existing and newly formed β cells need to be refined. This review provides a description of β cell ablation methods and a discussion of various types of studies of regenerative approaches-β cell proliferation, islet cell transplantation, transdifferentiation, and the use of embryonic and induced pluripotent stem cells-to the treatment of diabetes mellitus. Although there has been much progress in this area, further research is needed to enhance understanding and improve therapeutic strategies for this widespread disease.