5 years ago

Beta Cell Replacement in Mice Using Human Type 1 Diabetes Nuclear Transfer Embryonic Stem Cells.

Beta cells derived from stem cells hold great promise for cell replacement therapy for diabetes. Here we examine the ability of nuclear transfer embryonic stem cells (NT-ES) derived from a type 1 diabetes patient to differentiate into beta cells, and provide a source of autologous islets for cell replacement. NT-ES cells differentiate in vitro with an average efficiency of 55% into C-peptide-positive cells, expressing markers of mature beta cells, including MAFA and NKX6.1. Upon transplantation in immunodeficient mice, grafted cells form vascularized islet-like structures containing MAFA/C-peptide-positive cells. These beta cells adapt insulin secretion to ambient metabolite status and show normal insulin processing. Importantly, NT-ES-beta cells maintain normal blood glucose levels after ablation of the mouse's endogenous beta cells. Cystic structures, but no teratomas, were observed in NT-ES-beta cell grafts. Isogenic induced pluripotent stem cell lines showed greater variability in beta cell differentiation. Even though different methods of somatic cell reprogramming result in stem cell lines that are molecularly indistinguishable, full differentiation competence is more common in ES cell lines than in iPS cell lines. These results demonstrate the suitability of NT-ES-beta for cell replacement for type 1 diabetes, and provide proof of principle for therapeutic cloning combined with cell therapy.

Publisher URL: http://doi.org/10.2337/db17-0120

DOI: 10.2337/db17-0120

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