@article{a02c0c93503d443f944378d63676a0bf,
title = "Fail-Safe System against Potential Tumorigenicity after Transplantation of iPSC Derivatives",
abstract = "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.",
keywords = "iCaspase9, iPSC-derived neural stem/progenitor cells (iPSC-NS/PCs), induced pluripotent stem cells (iPSCs), spinal cord injury",
author = "Go Itakura and Soya Kawabata and Miki Ando and Yuichiro Nishiyama and Keiko Sugai and Masahiro Ozaki and Tsuyoshi Iida and Toshiki Ookubo and Kota Kojima and Rei Kashiwagi and Kaori Yasutake and Hiromitsu Nakauchi and Hiroyuki Miyoshi and Narihito Nagoshi and Jun Kohyama and Akio Iwanami and Morio Matsumoto and Masaya Nakamura and Hideyuki Okano",
note = "Funding Information: We appreciate the help of Dr. S. Shibata, Dr. F. Renault-Mihara, Dr. M. Shinozaki, Dr. S. Tashiro, Dr. K. Matsubayashi, Dr. K. Ito, Dr. Y. Tanimoto, Dr. Y. Hoshino, Dr. Y. Fukushima, and Ms. M. Isoda who are all members of the spinal cord research team at the Department of Physiology, Orthopedic Surgery and Rehabilitation Medicine, Keio University School of Medicine, Tokyo, Japan. We also thank Prof. Douglass Sipp (Keio University) for invaluable comments on the manuscript and Ms. T. Harada for assistance with animal care. We also thank Dr. S. Yamanaka and M. Ando for the human iPSC clones (253G1 and TKDA3-4). This work was supported by the Research Center Network for Realization of Regenerative Medicine by the Japan Science and Technology Agency (JST) and the Japan Agency for Medical Research and Development (AMED) (grant no. 16bm0204001h0004 to H.O. and M.N.), a Grant-in-Aid for Scientific Research by Japan Society for the Promotion of Science (grant no. 15K10422 to A.I.), and a grant by The General Insurance Association of Japan (grant no. 15-2B-13 to A.I.). H.O. is a founding scientist and a paid SAB of San Bio, Co., Ltd. Publisher Copyright: {\textcopyright} 2017 The Authors",
year = "2017",
month = mar,
day = "14",
doi = "10.1016/j.stemcr.2017.02.003",
language = "English",
volume = "8",
pages = "673--684",
journal = "Stem Cell Reports",
issn = "2213-6711",
publisher = "Cell Press",
number = "3",
}
