Fail-Safe System against Potential Tumorigenicity after Transplantation of iPSC Derivatives

Go Itakura, Soya Kawabata, Miki Ando, Yuichiro Nishiyama, Keiko Sugai, Masahiro Ozaki, Tsuyoshi Iida, Toshiki Ookubo, Kota Kojima, Rei Kashiwagi, Kaori Yasutake, Hiromitsu Nakauchi, Hiroyuki Miyoshi, Narihito Nagoshi, Jun Kohyama, Akio Iwanami, Morio Matsumoto, Masaya Nakamura, Hideyuki Okano

研究成果: Article査読

46 被引用数 (Scopus)

抄録

Human induced pluripotent stem cells (iPSCs) are promising in regenerative medicine. However, the risks of teratoma formation and the overgrowth of the transplanted cells continue to be major hurdles that must be overcome. Here, we examined the efficacy of the inducible caspase-9 (iCaspase9) gene as a fail-safe against undesired tumorigenic transformation of iPSC-derived somatic cells. We used a lentiviral vector to transduce iCaspase9 into two iPSC lines and assessed its efficacy in vitro and in vivo. In vitro, the iCaspase9 system induced apoptosis in approximately 95% of both iPSCs and iPSC-derived neural stem/progenitor cells (iPSC-NS/PCs). To determine in vivo function, we transplanted iPSC-NS/PCs into the injured spinal cord of NOD/SCID mice. All transplanted cells whose mass effect was hindering motor function recovery were ablated upon transduction of iCaspase9. Our results suggest that the iCaspase9 system may serve as an important countermeasure against post-transplantation adverse events in stem cell transplant therapies.

本文言語English
ページ(範囲)673-684
ページ数12
ジャーナルStem Cell Reports
8
3
DOI
出版ステータスPublished - 14-03-2017
外部発表はい

All Science Journal Classification (ASJC) codes

  • 生化学
  • 遺伝学
  • 発生生物学
  • 細胞生物学

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