Development of Methods to Inhibit Tumorigenesis after Transplantation of Differentiated iPS Cells

Abstract

There are problems that tumor-like cells appear in transplantation therapy using iPS cells (iPSCs). Contamination and proliferation of undifferentiated cells that do not respond to differentiation induction cause tumorigenesis. The iPSCs grafts require completely differentiated cells and/or tissues in vitro unlike the mesenchymal stem cells. In this report, we survey recent topics in prevention of tumorigenesis risks of iPSCs with referring the knowledge from our experiments. Undifferentiated iPSCs extremely resemble to ES cells by transmission electron microscope analysis. The resistant undifferentiated cells after induction were detected by fluorescent microscope and flow cytometer. These cells were selectively eliminated by fluorescent labeling plus laser and radiation exposures. By irradiation to differentiated cells, GFP positive cells, those are undifferentiated iPS cells, were decreased without disorder in myocardial beats. Irradiated iPS cells were also injected into the testis of SCID mouse to examine teratoma formations. Although non-irradiated cells formed teratomas in all the mice examined, irradiated cells formed no teratoma and localized in the testis. Thus, it was suggested that irradiation before the transplantation selectively eliminates residual undifferentiated cells and inhibits post transplantation tumorigenesis in mouse iPSCs. Irradiation will be possible to cell / tissues before transplantation of human iPSCs. It is necessary to perform analysis of the cellular safety included the influence of gene functions in differentiated normal cells by irradiation.