Shinya Yamanaka：特定因子诱导的多能性

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Induction of pluripotency by defined factors
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4 E3 ?/ W: w0 E: e0 bShinya Yamanaka
0 m" C: C2 }6 w(Kyoto University, Japan)& _+ L& T7 W7 C6 H- y6 m+ d1 m% }2 V

5 ?( K' {5 B- z% aHuman ES cells have been expected as suitable resources for cell transplantation therapies. However, it has sparked ethical controversy and causes immune rejection. Hence, we decided to generate an ideal pluripotent stem cell for innovative medicine.
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5 v: }3 K+ R# M6 i! [7 Q% CAt first, we constructed a pluripotency assay system that the candidate factors are introduced into neonate fibroblasts via retrovirus vectors. 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 cells in terms of morphology and proliferation showed ES cell markers and formed teratoma. It was named as induced pluripotent stem cell (iPS cell). iPS cells were created even from adult mouse fi broblasts. Moreover, iPS cells based on Nanog-expression demonstrated germline transmission. Furthermore, we successfully generated iPS cells from human adult fi broblasts, using a modifi ed protocol.; B3 _9 i6 C1 s# K2 B3 V

, t+ x% k4 i9 @However, tumor formation was observed in chimera mouse, probably due to c-Myc retrovirus integrated into genome. We re-modified the protocol and successfully established iPS cells without using c-Myc. As further effort to lower a risk of tumorigenesis, we recently succeeded in developing a virus-free method - using a pair of plasmid vectors, instead of retrovirus vectors, to introduce the four genes into mouse fi broblasts.% c( m3 ?, e$ V

9 B8 _8 P/ T3 M2 B1 n  y8 e6 t( }Further research results are discussed from the points of safety and induction efficiency of iPS cells for future clinical grade.

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