title: Repair of Ischemic Injury by Pluripotent Stem Cell Based Cell Therapy without Teratoma through Selective Photosensitivity.
abstract: Stem-toxic small molecules have been developed to induce selective cell death of pluripotent stem cells (PSCs) to lower the risk of teratoma formation. However, despite their high efficacies, chemical-based approaches may carry unexpected toxicities on specific differentiated cell types. Herein, we took advantage of KillerRed (KR) as a suicide gene, to selectively induce phototoxicity using visible light via the production of reactive oxygen species. PSCs in an undifferentiated state that exclusively expressed KR (KR-PSCs) were eliminated by a single exposure to visible light. This highly selective cell death in KR-PSCs was exploited to successfully inhibit teratoma formation. In particular, endothelial cells from KR-mPSCs remained fully functional in vitro and sufficient to repair ischemic injury in vivo regardless of light exposure, suggesting that a genetic approach in which KR is expressed in a tightly controlled manner would be a viable strategy to inhibit teratoma formation for future safe PSC-based therapies.
authors.affiliation: Department of Life Sciences, College of Natural Sciences, Sogang University, Seoul 121-742, Korea.
authors.forename: Seung-Ju
authors.initials: SJ
authors.lastname: Cho
authors.affiliation: Department of Life Sciences, College of Natural Sciences, Sogang University, Seoul 121-742, Korea.
authors.forename: So-Yeon
authors.initials: SY
authors.lastname: Kim
authors.affiliation: Department of Life Sciences, College of Natural Sciences, Sogang University, Seoul 121-742, Korea.
authors.forename: Ho-Chang
authors.initials: HC
authors.lastname: Jeong
authors.affiliation: Department of Physics, College of Natural Sciences, Sogang University, Seoul 121-742, Korea.
authors.forename: Hyeonsik
authors.initials: H
authors.lastname: Cheong
authors.affiliation: Department of Physics, College of Natural Sciences, Sogang University, Seoul 121-742, Korea.
authors.forename: Doseok
authors.initials: D
authors.lastname: Kim
authors.affiliation: Department of Stem Cell Biology, School of Medicine, Konkuk University, Seoul 143-701, Korea.
authors.forename: Soon-Jung
authors.initials: SJ
authors.lastname: Park
authors.affiliation: Department of Stem Cell Biology, School of Medicine, Konkuk University, Seoul 143-701, Korea.
authors.forename: Jong-Jin
authors.initials: JJ
authors.lastname: Choi
authors.affiliation: Graduate School of Biomedical Science and Engineering, College of Medicine, Hanyang University, Seoul 133-791, Korea.
authors.forename: Hyongbum
authors.initials: H
authors.lastname: Kim
authors.affiliation: Department of Stem Cell Biology, School of Medicine, Konkuk University, Seoul 143-701, Korea.
authors.forename: Hyung-Min
authors.initials: HM
authors.lastname: Chung
authors.affiliation: Department of Medicine, School of Medicine, Konkuk University, Seoul 143-701, Korea. Electronic address: sunghwanmoon@kku.ac.kr.
authors.forename: Sung-Hwan
authors.initials: SH
authors.lastname: Moon
authors.affiliation: Department of Life Sciences, College of Natural Sciences, Sogang University, Seoul 121-742, Korea. Electronic address: hjcha@sogang.ac.kr.
authors.forename: Hyuk-Jin
authors.initials: HJ
authors.lastname: Cha
mesh_terms: D000818:Animals; D016923:Cell Death / Q000528:radiation effects; D002454:Cell Differentiation; D064987:Cell- and Tissue-Based Therapy; D042783:Endothelial Cells / Q000166:cytology / Q000637:transplantation*; D005260:Female; D006614:Hindlimb / Q000098:blood supply; D007511:Ischemia / Q000628:therapy*; D008027:Light; D051379:Mice; D008819:Mice, Nude; D039904:Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism / Q000528:radiation effects*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013724:Teratoma / Q000517:prevention & control*
chemical_list: D017382:Reactive Oxygen Species
keywords: KillerRed; ischemic injury; phototoxicity; pluripotent stem cells; teratoma; vasculogenesis