A simple, robust and scalable method of directed differentiation of human pluripotent stem cells, including embryonic stem (hES) cells and induced pluripotent stem (iPS) cells, generates insulin-producing cells in vitro that have reversed diabetes in vivo and in diabetic mice. A simple, broadly applicable four-step process demonstrates that hES and human iPS cells from dermal fibroblast cells generate insulin-producing cells. Insulin expression and secretion was detected from iPS-derived cells in vitro and in vivo by qPCR, and c-peptide release was confirmed by immunostaining. These results suggest that the method is robust enough to work with a range of cell types, meaning that iPS cells derived from diabetic patient somatic cells are not only a potential, but a highly attractive, source of cells for transplantation. The technology may also work using individual donor cell lines, making both autologous and allogeneic transplantation therapies possible.
Previous attempts at deriving insulin-secreting cells are not optimal: They are complex, complicated, multiple-step processes involving many added cytokines and growth factors as well as the toxic chemical cyclopamine. These methods also lack significant expansion of cell numbers. Islet replacement therapy is promising but suffers from limited availability of donor tissues. This method requires only four steps, uses a limited number of growth factors, and achieves similar results using a monoclonal antibody instead of toxic chemicals. Furthermore, it achieves expansion of cells during the process.
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multiple-step processes involving
islet replacement therapy
induced pluripotent stem
toxic chemical cyclopamine
lack significant expansion