Establishment of the cell therapy for liver failure using hepatocytes derived from induced pluripotent stem cells

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The purposes of this study are 1) to generate induced pluripotent stem (iPS) cells from the mouse tail, 2) to differentiate iPS cells to functional hepatocytes, and 3) to autograft differentiated cells into mice with liver failure. We isolated mouse fibroblast from mouse tail, transduced Oct3/4, Sox2, Klf4, c-Myc genes by using retroviral vectors established in Kyoto University, and generated mouse iPS cell lines. These mouse iPS cells were successfully differentiated into hepatocyte-like cells with supplementation of several growth factors and chemicals. We modified and improved the differentiation protocol and transplanted these cells into the portal vein of the immunodeficiency mouse, but teratomas were still formed. We conclude that further improvement of differentiation protocol for iPS cells is required to establish cell therapy for liver failure patients.