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

• Main Authors: 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
• Format: Article
• Language: English
• Published: Elsevier 2017-03-01
• Series: Stem Cell Reports
• Subjects: induced pluripotent stem cells (iPSCs); iCaspase9; iPSC-derived neural stem/progenitor cells (iPSC-NS/PCs); spinal cord injury
• Online Access: http://www.sciencedirect.com/science/article/pii/S2213671117300474

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.