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Strategies Toward Beta-Cell Replacement

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Trends in Stem Cell Biology and Technology

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Abstract

Embryonic and adult stem cells are considered to be potential sources of insulin-secreting cells to be transplanted into type 1 and advanced stages of type 2 diabetic patients. After years of study, the key determinants necessary for the differentiation process are beginning to be fully characterised, and several protocols have been published. However, investigators still have to face several problems before finding a therapeutic application, such as to increase the amount of insulin produced by the final cell product, to examine the processing of the hormone in these protocols, and to confirm the existence of a stimulus-coupled secretory process. Concerning transplantation, we must also pay attention to implant survival, tumour formation, and immune rejection. Mimicking endocrine pancreas development in vitro seems to yield the best results in terms of obtaining insulin-secreting cells from embryonic stem cells. To this end, definitive endoderm precursors have been generated. The final cell product contained amounts of insulin and phenotypic traits similar to mature β cells. However, these cells seemed to be immature, since they did not respond to stimulatory concentrations of extracellular glucose and coexpressed two hormones in the same cell (insulin glucagon, insulin somatostatin). Therefore, further improvements are required. Concerning adult stem cells, the possibility of identifying pancreatic precursors or of reprogramming extrapancreatic-derived cells are key possibilities that may circumvent some of the problems that appear when using embryonic stem cells. However, current protocols are not capable of obtaining a functional cell product useful for therapeutic purposes. The identification of signals that operate in vivo in the different niches could help in the design of more adequate strategies.

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  1. Instituto de Bioingenieria, Universidad Miguel Hernandez, Alicante, Spain

    Enrique Roche, Nestor Vicente-Salar, Maribel Arribas & Beatriz Paredes

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  1. Enrique Roche
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    Roche, E., Vicente-Salar, N., Arribas, M., Paredes, B. (2009). Strategies Toward Beta-Cell Replacement. In: Baharvand, H. (eds) Trends in Stem Cell Biology and Technology. Humana Press. https://doi.org/10.1007/978-1-60327-905-5_17

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