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

Abstract

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.