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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 β-cell replacement, as well as control of the autoimmune response to cells which express insulin. The ex vivo generation of β cells suitable for transplantation to reconstitute a functional β-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.

Key Points

  • A definitive cure for type 1 diabetes mellitus (T1DM) will address both the β-cell deficit and the autoimmune response to cells that express insulin

  • Cells that express insulin have been obtained through differentiation of stem cells of either embryonic or adult origin, as well as genetically reprogrammed and transdifferentiated cells

  • The most effective differentiation protocols for the derivation of cells that express insulin recapitulate normal embryonic development

  • Knowledge of the transcription factors that regulate development of the embryonic pancreas has aided the evaluation of different strategies used to obtain β cells

  • Clinical trials have used bone marrow-derived mesenchymal stromal cells and umbilical cord blood cells to suppress the immune response in patients with T1DM

  • Even though challenges remain, the possibility of an effective stem-cell therapy for T1DM is a realistic goal for the foreseeable future

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Figure 1: Generation of insulin-expressing cells from pluripotent cells.
Figure 2: Strategies to obtain β cells from organ-specific stem or progenitor cells.

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Aguayo-Mazzucato, C., Bonner-Weir, S. Stem cell therapy for type 1 diabetes mellitus. Nat Rev Endocrinol 6, 139–148 (2010). https://doi.org/10.1038/nrendo.2009.274

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