@article{44e45014c8e74211878ddb91f84cab4d,
title = "Pathological classification of human iPSC-derived neural stem/progenitor cells towards safety assessment of transplantation therapy for CNS diseases",
abstract = "The risk of tumorigenicity is a hurdle for regenerative medicine using induced pluripotent stem cells (iPSCs). Although teratoma formation is readily distinguishable, the malignant transformation of iPSC derivatives has not been clearly defined due to insufficient analysis of histology and phenotype. In the present study, we evaluated the histology of neural stem/progenitor cells (NSPCs) generated from integration-free human peripheral blood mononuclear cell (PBMC)-derived iPSCs (iPSC-NSPCs) following transplantation into central nervous system (CNS) of immunodeficient mice. We found that transplanted iPSC-NSPCs produced differentiation patterns resembling those in embryonic CNS development, and that the microenvironment of the final site of migration affected their maturational stage. Genomic instability of iPSCs correlated with increased proliferation of transplants, although no carcinogenesis was evident. The histological classifications presented here may provide cues for addressing potential safety issues confronting regenerative medicine involving iPSCs.",
keywords = "Carcinogenesis, Cell transplantation, Human induced pluripotent stem cells, Pathology, Regenerative medicine",
author = "Keiko Sugai and Ryuji Fukuzawa and Tomoko Shofuda and Hayato Fukusumi and Soya Kawabata and Yuichiro Nishiyama and Yuichiro Higuchi and Kenji Kawai and Miho Isoda and Daisuke Kanematsu and Tomoko Hashimoto-Tamaoki and Jun Kohyama and Akio Iwanami and Hiroshi Suemizu and Eiji Ikeda and Morio Matsumoto and Yonehiro Kanemura and Masaya Nakamura and Hideyuki Okano",
note = "Funding Information: This work was supported in part by grants from the Japan Science and Technology (JST)–California Institute for Regenerative Medicine (CIRM) Collaborative Program; Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (SPS) and the Ministry of Education, Culture, Sports, Science and Technology of Japan (MEXT); and a grant from the Research Center Network for Realization of Regenerative Medicine from JST and Japan Agency for Medical Research and Development (AMED) (to H.O., M.N. and Y.K.). We also thank the Research Center Network for Realization of Regenerative Medicine for financially supporting our work, as well as the Japan Science and Technology Agency (JST) and the Japan Agency for Medical Research and Development (AMED). Publisher Copyright: {\textcopyright} 2016 The Author(s).",
year = "2016",
month = sep,
day = "19",
doi = "10.1186/s13041-016-0265-8",
language = "English",
volume = "9",
journal = "Molecular brain",
issn = "1756-6606",
publisher = "BioMed Central",
number = "1",
}
