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Stem Cell Reports. 2015 Dec 8;5(6):1067-1080. doi: 10.1016/j.stemcr.2015.10.004. Epub 2015 Nov 12.

Repair of Ischemic Injury by Pluripotent Stem Cell Based Cell Therapy without Teratoma through Selective Photosensitivity.

Author information

1
Department of Life Sciences, College of Natural Sciences, Sogang University, Seoul 121-742, Korea.
2
Department of Physics, College of Natural Sciences, Sogang University, Seoul 121-742, Korea.
3
Department of Stem Cell Biology, School of Medicine, Konkuk University, Seoul 143-701, Korea.
4
Graduate School of Biomedical Science and Engineering, College of Medicine, Hanyang University, Seoul 133-791, Korea.
5
Department of Medicine, School of Medicine, Konkuk University, Seoul 143-701, Korea. Electronic address: sunghwanmoon@kku.ac.kr.
6
Department of Life Sciences, College of Natural Sciences, Sogang University, Seoul 121-742, Korea. Electronic address: hjcha@sogang.ac.kr.

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.

KEYWORDS:

KillerRed; ischemic injury; phototoxicity; pluripotent stem cells; teratoma; vasculogenesis

PMID:
26584542
PMCID:
PMC4682089
DOI:
10.1016/j.stemcr.2015.10.004
[Indexed for MEDLINE]
Free PMC Article

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