Recent advance in induced pluripotent stem cells

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  • Okita Keisuke
    Center for iPS Cell Research and Application (CiRA), Institute for Integrated Cell-Material Sciences, KyotoUniversity, Kyoto, Japan
  • Yamanaka Shinya
    Center for iPS Cell Research and Application (CiRA), Institute for Integrated Cell-Material Sciences, KyotoUniversity, Kyoto, Japan Department of Stem Cell Biology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto, Japan CREST and Yamanaka iPS Cell Project, Japan Science and Technology Agency, Kawaguchi, Japan Gladstone Institute of Cardiovascular Disease, San Francisco, CA 94158

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We have previously shown that embryonic stem (ES)-like cells can be induced from mouse fibroblasts, hepatocytes and stomach epithelial cells by introducing four factors (Oct3/4, Sox2, c-Myc, and Klf4). The cells are similar in morphology, proliferation and gene expression profile to those of ES cells, and are called induced pluripotent stem (iPS) cells. When the iPS cells are transferred into blastocyst, they can contribute to adult chimeric mice and transmit through germline to the next generation. Therefore iPS cells have almost same differentiation potential as ES cells. In 2007, we and others reported the establishment of iPS cells from human somatic cells and showed their pluripotency.<BR>These iPS cells would supply patient-specific pluripotent stem cells for cell transplantation therapies. However, iPS cells still have several problems to be overcome, especially tumorigenicity owing to the use of oncogenes and retrovirus. Recent studies revealed that c-Myc is not a crucial factor for iPS induction, albeit it greatly increases the efficiency. The improvement of reprogramming efficiency was reported with soluble factor, Wnt3a, and several small molecules that influence epigenetic modification, such as BIX-01294 and VPA. Induction of mouse iPS cells without virus vector has been reported. Through the basic researches on iPS and ES cells, molecular mechanisms underlying the reprogramming process were gradually being uncovered. Here we try to summarize current studies on iPS cells. The iPS cells will contribute to the fields ofelucidation of pathogenesis, drug discovery, toxicology study, and cell transplantation therapy in the future.

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