Abstract: Series 104, Lecture 5
The Harvey Lectures Series 104 (2008—2009)
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Lecture #5: Thursday, March 19, 2009 — Time and Location
iPS Cells-Perspective and Challenge
Shinya Yamanaka, MD, PhD
Professor and Director Center for iPS Cell Research and Application (CIRA)
Institute for Integrated Cell-Material Sciences (iCeMS)
Kyoto University
Kyoto, Japan
Human ES cell has been expected as suitable resource for cell transplantation therapies. However, it has ethical controversy and immune rejection. Hence, we decided to generate an ideal pluripotent stem cell for innovative medicine. At first, we constructed pluripotency assay system that the candidate factors be retrovirus vector-via introduced into neonate fibroblast. As the result, the set of Oct3/4, Sox2, c-Myc, and Klf-4 gave rise to drug resistant colonies, implying potential pluripotency. The survived cells resembled ES cell on morphology and proliferation, showed ES cell markers, and formed teratoma. It was named for induced pluripotent Stem cell (iPS cell). Even from adult mouse fibroblast, iPS cell was obtained. Moreover, iPS cell based on Nanog-expression demonstrated germline transmission. Furthermore, modified protocol successfully generated iPS cell from human adult fibroblast. However, tumor formation had been observed in chimera mouse, probably due to c-Myc integrated into genome. We re-modified protocol, and successfully established iPS cell without c-Myc. Further research results will be discussed from the points of safety and induction efficiency of iPS cell for future clinical grade.