@article{676940c756c8447a9c31c3c8acb0353b,
title = "Pretreatment with a γ-Secretase Inhibitor Prevents Tumor-like Overgrowth in Human iPSC-Derived Transplants for Spinal Cord Injury",
abstract = "Neural stem/progenitor cells (NS/PCs) derived from human induced pluripotent stem cells (hiPSCs) are considered to be a promising cell source for cell-based interventions that target CNS disorders. We previously reported that transplanting certain hiPSC-NS/PCs in the spinal cord results in tumor-like overgrowth of hiPSC-NS/PCs and subsequent deterioration of motor function. Remnant immature cells should be removed or induced into more mature cell types to avoid adverse effects of hiPSC-NS/PC transplantation. Because Notch signaling plays a role in maintaining NS/PCs, we evaluated the effects of γ-secretase inhibitor (GSI) and found that pretreating hiPSC-NS/PCs with GSI promoted neuronal differentiation and maturation in vitro, and GSI pretreatment also reduced the overgrowth of transplanted hiPSC-NS/PCs and inhibited the deterioration of motor function in vivo. These results indicate that pretreatment with hiPSC-NS/PCs decreases the proliferative capacity of transplanted hiPSC-NS/PCs, triggers neuronal commitment, and improves the safety of hiPSC-based approaches in regenerative medicine.",
author = "Toshiki Okubo and Akio Iwanami and Jun Kohyama and Go Itakura and Soya Kawabata and Yuichiro Nishiyama and Keiko Sugai and Masahiro Ozaki and Tsuyoshi Iida and Kohei Matsubayashi and Morio Matsumoto and Masaya Nakamura and Hideyuki Okano",
note = "Funding Information: We appreciate the assistance of Drs. N. Nagoshi, K. Kojima, and S. Ito, who are all members of the spinal cord research team in the Department of Orthopedic Surgery, Keio University School of Medicine, Tokyo, Japan. We also thank Ms. T. Harada, Ms. R. Kashiwagi, and Ms. K. Yasutake for their assistance with the experiments and animal care. We thank Prof. Douglass Sipp (Keio University) for providing invaluable comments on the manuscript. This work was supported by Research Center Network for Realization of Regenerative Medicine from the Japan Science and Technology Agency (JST), the Japan Agency for Medical Research and Development (AMED) (grant no. 15bm0204001h0003 to H.O. and M.N.), and in part by a medical research grant on traffic accidents from The General Insurance Association of Japan (grant no. 15-1-42 ). H.O. is a compensated scientific consultant of San Bio, Co., Ltd. Publisher Copyright: {\textcopyright} 2016 The Authors Copyright: Copyright 2017 Elsevier B.V., All rights reserved.",
year = "2016",
month = oct,
day = "11",
doi = "10.1016/j.stemcr.2016.08.015",
language = "English",
volume = "7",
pages = "649--663",
journal = "Stem cell reports",
issn = "2213-6711",
publisher = "Cell Press",
number = "4",
}