Stem cell therapy for type 1 diabetes mellitus

Abstract

The use of stem cells in regenerative medicine holds great promise for the cure of many diseases, including type 1 diabetes mellitus (T1DM). Any potential stem-cell-based cure for T1DM should address the need for beta-cell replacement, as well as control of the autoimmune response to cells which express insulin. The ex vivo generation of beta cells suitable for transplantation to reconstitute a functional beta-cell mass has used pluripotent cells from diverse sources, as well as organ-specific facultative progenitor cells from the liver and the pancreas. The most effective protocols to date have produced cells that express insulin and have molecular characteristics that closely resemble bona fide insulin-secreting cells; however, these cells are often unresponsive to glucose, a characteristic that should be addressed in future protocols. The use of mesenchymal stromal cells or umbilical cord blood to modulate the immune response is already in clinical trials; however, definitive results are still pending. This Review focuses on current strategies to obtain cells which express insulin from different progenitor sources and highlights the main pathways and genes involved, as well as the different approaches for the modulation of the immune response in patients with T1DM.