Chemical and metabolic control of pluripotent stem cell differentiation into pancreatic β cells

Abstract
ES cells and iPS cells are considered to be potential alternative cell sources for the transplantation therapy as well as cell models for biological studies. Up to date, studies to generate the pancreatic beta cells from pluripotent stem cells have achieved remarkable progresses. However, it still remain elusive whether the derived pancreatic beta cells resemble the human beta cells and could be used in clinical settings.

We have been trying to improve the efficiency of differentiation and the maturation of the derived insulin-producing beta cells from human ES/iPS cells, through screening for novel small molecular compounds that promote differentiation and/or proliferation of pancreatic beta-cells. We identified molecules that function in regulating pancreatic beta cell differentiation and dedifferentiation.

Besides chemical screening, we also analyzed the importance of amino acids in the media. We found that methionine metabolism is crucial for the maintenance of pluripotency in human pluripotent cells. Deprival of methionine rendered the cells at a poised state for differentiation, and thus increased the efficiency for differentiation.

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