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...

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Main Authors: 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
Format: Article
Language:English
Published: Elsevier 2015-12-01
Series:Stem Cell Reports
Subjects:
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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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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