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

Stem Cell Reports

So-Yeon Kim¹  Ho-Chang Jeong¹  Hyuk-Jin Cha¹  Seung-Ju Cho¹  Sung-Hwan Moon²  Hyeonsik Cheong³  Doseok Kim³  Jong-Jin Choi⁴  Hyung-Min Chung⁴  Soon-Jung Park⁴  Hyongbum Kim⁵ 

[1] Department of Life Sciences, College of Natural Sciences, Sogang University, Seoul 121-742, Korea;Department of Medicine, School of Medicine, Konkuk University, Seoul 143-701, Korea;Department of Physics, College of Natural Sciences, Sogang University, Seoul 121-742, Korea;Department of Stem Cell Biology, School of Medicine, Konkuk University, Seoul 143-701, Korea;Graduate School of Biomedical Science and Engineering, College of Medicine, Hanyang University, Seoul 133-791, Korea;

关键词: pluripotent stem cells;    KillerRed;    phototoxicity;    teratoma;    ischemic injury;    vasculogenesis;   

DOI  :  10.1016/j.stemcr.2015.10.004

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown