Here, the scientists highlight prominent tumorigenic risks of iPSC products, especially when reprogrammed with integrating vectors. Two major underlying mechanisms in iPSC tumorigenicity are residual pluripotent cells and cMYC overload by vector integration.They demonstrate that combined transgene-free (TGF) reprogramming using nonintegrating Sendai viral vectors and enzymatic dissociation allow teratoma-free transplantation of iPSC progeny in the most rigorous mouse model in testing the tumorigenicity of iPSC products.Further long-term safety assessment and improvement in TGF-iPSC specification into a mature b-cell phenotype would lead to customized safe islet replacement therapy for type 1 diabetes.
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Here, the scientists highlight prominent tumorigenic risks of iPSC products, especially when reprogrammed with integrating vectors. Two major underlying mechanisms in iPSC tumorigenicity are residual pluripotent cells and cMYC overload by vector integration.They demonstrate that combined transgene-free (TGF) reprogramming using nonintegrating Sendai viral vectors and enzymatic dissociation allow teratoma-free transplantation of iPSC progeny in the most rigorous mouse model in testing the tumorigenicity of iPSC products.Further long-term safety assessment and improvement in TGF-iPSC specification into a mature b-cell phenotype would lead to customized safe islet replacement therapy for type 1 diabetes.