Repair of Ischemic Injury by Pluripotent Stem Cell Based Cell Therapy without Teratoma through Selective Photosensitivity
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...
Main Authors: | , , , , , , , , , , |
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Format: | Article |
Language: | English |
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Elsevier
2015-12-01
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Series: | Stem Cell Reports |
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Online Access: | http://www.sciencedirect.com/science/article/pii/S221367111500301X |
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author | Seung-Ju Cho So-Yeon Kim Ho-Chang Jeong Hyeonsik Cheong Doseok Kim Soon-Jung Park Jong-Jin Choi Hyongbum Kim Hyung-Min Chung Sung-Hwan Moon Hyuk-Jin Cha |
author_facet | Seung-Ju Cho So-Yeon Kim Ho-Chang Jeong Hyeonsik Cheong Doseok Kim Soon-Jung Park Jong-Jin Choi Hyongbum Kim Hyung-Min Chung Sung-Hwan Moon Hyuk-Jin Cha |
author_sort | Seung-Ju Cho |
collection | DOAJ |
description | 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. |
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id | doaj.art-ca32e091591740c0b2435fffaa5cba46 |
institution | Directory Open Access Journal |
issn | 2213-6711 |
language | English |
last_indexed | 2024-12-16T14:16:08Z |
publishDate | 2015-12-01 |
publisher | Elsevier |
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series | Stem Cell Reports |
spelling | doaj.art-ca32e091591740c0b2435fffaa5cba462022-12-21T22:28:37ZengElsevierStem Cell Reports2213-67112015-12-01561067108010.1016/j.stemcr.2015.10.004Repair of Ischemic Injury by Pluripotent Stem Cell Based Cell Therapy without Teratoma through Selective PhotosensitivitySeung-Ju Cho0So-Yeon Kim1Ho-Chang Jeong2Hyeonsik Cheong3Doseok Kim4Soon-Jung Park5Jong-Jin Choi6Hyongbum Kim7Hyung-Min Chung8Sung-Hwan Moon9Hyuk-Jin Cha10Department of Life Sciences, College of Natural Sciences, Sogang University, Seoul 121-742, KoreaDepartment of Life Sciences, College of Natural Sciences, Sogang University, Seoul 121-742, KoreaDepartment of Life Sciences, College of Natural Sciences, Sogang University, Seoul 121-742, KoreaDepartment of Physics, College of Natural Sciences, Sogang University, Seoul 121-742, KoreaDepartment of Physics, College of Natural Sciences, Sogang University, Seoul 121-742, KoreaDepartment of Stem Cell Biology, School of Medicine, Konkuk University, Seoul 143-701, KoreaDepartment of Stem Cell Biology, School of Medicine, Konkuk University, Seoul 143-701, KoreaGraduate School of Biomedical Science and Engineering, College of Medicine, Hanyang University, Seoul 133-791, KoreaDepartment of Stem Cell Biology, School of Medicine, Konkuk University, Seoul 143-701, KoreaDepartment of Medicine, School of Medicine, Konkuk University, Seoul 143-701, KoreaDepartment of Life Sciences, College of Natural Sciences, Sogang University, Seoul 121-742, KoreaStem-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.http://www.sciencedirect.com/science/article/pii/S221367111500301Xpluripotent stem cellsKillerRedphototoxicityteratomaischemic injuryvasculogenesis |
spellingShingle | Seung-Ju Cho So-Yeon Kim Ho-Chang Jeong Hyeonsik Cheong Doseok Kim Soon-Jung Park Jong-Jin Choi Hyongbum Kim Hyung-Min Chung Sung-Hwan Moon Hyuk-Jin Cha Repair of Ischemic Injury by Pluripotent Stem Cell Based Cell Therapy without Teratoma through Selective Photosensitivity Stem Cell Reports pluripotent stem cells KillerRed phototoxicity teratoma ischemic injury vasculogenesis |
title | Repair of Ischemic Injury by Pluripotent Stem Cell Based Cell Therapy without Teratoma through Selective Photosensitivity |
title_full | Repair of Ischemic Injury by Pluripotent Stem Cell Based Cell Therapy without Teratoma through Selective Photosensitivity |
title_fullStr | Repair of Ischemic Injury by Pluripotent Stem Cell Based Cell Therapy without Teratoma through Selective Photosensitivity |
title_full_unstemmed | Repair of Ischemic Injury by Pluripotent Stem Cell Based Cell Therapy without Teratoma through Selective Photosensitivity |
title_short | Repair of Ischemic Injury by Pluripotent Stem Cell Based Cell Therapy without Teratoma through Selective Photosensitivity |
title_sort | repair of ischemic injury by pluripotent stem cell based cell therapy without teratoma through selective photosensitivity |
topic | pluripotent stem cells KillerRed phototoxicity teratoma ischemic injury vasculogenesis |
url | http://www.sciencedirect.com/science/article/pii/S221367111500301X |
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