Lysine-specific demethylase 1 inhibitors prevent teratoma development from human induced pluripotent stem cells
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Naoki Osada1, Jiro Kikuchi1, Takashi Umehara2, Shin Sato2, Masashi Urabe3, Tomoyuki Abe4, Nakanobu Hayashi5, Masahiko Sugitani6, Yutaka Hanazono4 and Yusuke Furukawa1
1Division of Stem Cell Regulation, Center for Molecular Medicine, Jichi Medical University, Shimotsuke, Tochigi 329-0498, Japan
2Epigenetic Drug Discovery Unit, RIKEN Center for Life Science Technologies, Yokohama, Kanagawa 230-0045, Japan
3Division of Cell and Gene Therapy, Center for Molecular Medicine, Jichi Medical University, Shimotsuke, Tochigi, 329-0498, Japan
4Division of Regenerative Medicine, Center for Molecular Medicine, Jichi Medical University, Shimotsuke, Tochigi 329-0498, Japan
5Gene Try Company, Itabashi, Tokyo 173-8610, Japan
6Department of Pathology, Nihon University School of Medicine, Itabashi, Tokyo 173-8610, Japan
Jiro Kikuchi, email: [email protected]
Keywords: LSD1; small molecule inhibitor; teratoma; iPS; regenerative medicine
Received: November 01, 2017 Accepted: January 02, 2018 Published: January 08, 2018
Human induced pluripotent stem cells (hiPSCs) are creating great expectations for regenerative medicine. However, safety strategies must be put in place to guard against teratoma formation after transplantation of hiPSC-derived cells into patients. Recent studies indicate that epigenetic regulators act at the initial step of tumorigenesis. Using gain-of-function and loss-of-function approaches, we show here that the expression and function of lysine-specific demethylase 1 (LSD1) are tightly regulated in hiPSCs, and their deregulation underlies the development of teratomas. Consistent with these results, we demonstrate that an LSD1 inhibitor, S2157, prevented teratoma formation from hiPSCs transplanted into immunodeficient mice. This novel action of LSD1 and the effects of its inhibition potentially allow for the development of new clinical applications and therapeutic strategies using hiPSCs.
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