Luteolin Induces Selective Cell Death of Human Pluripotent Stem Cells
Despite recent advances in clinical stem cell therapy applications based on human pluripotent stem cells (hPSCs), potential teratoma formation due to the presence of residual undifferentiated hPSCs remains a serious risk factor that challenges widespread clinical application. To overcome this risk,...
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MDPI AG
2020-10-01
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Online Access: | https://www.mdpi.com/2227-9059/8/11/453 |
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author | Young-Hyun Go Jumee Kim Ho-Chang Jeong Seong-Min Kim Yun-Jeong Kim Soon-Jung Park Sung-Hwan Moon Hyuk-Jin Cha |
author_facet | Young-Hyun Go Jumee Kim Ho-Chang Jeong Seong-Min Kim Yun-Jeong Kim Soon-Jung Park Sung-Hwan Moon Hyuk-Jin Cha |
author_sort | Young-Hyun Go |
collection | DOAJ |
description | Despite recent advances in clinical stem cell therapy applications based on human pluripotent stem cells (hPSCs), potential teratoma formation due to the presence of residual undifferentiated hPSCs remains a serious risk factor that challenges widespread clinical application. To overcome this risk, a variety of approaches have been developed to eliminate the remaining undifferentiated hPSCs via selective cell death induction. Our study seeks to identify natural flavonoids that are more potent than quercetin (QC), to selectively induce hPSC death. Upon screening in-house flavonoids, luteolin (LUT) is found to be more potent than QC to eliminate hPSCs in a p53-dependent manner, but not hPSC-derived smooth muscle cells or perivascular progenitor cells. Particularly, treating human embryonic stem cell (hESC)-derived cardiomyocytes with LUT efficiently eliminates the residual hESCs and only results in marginal effects on cardiomyocyte (CM) functions, as determined by calcium influx. Considering the technical limitations of isolating CMs due to a lack of exclusive surface markers at the end of differentiation, LUT treatment is a promising approach to minimize teratoma formation risk. |
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institution | Directory Open Access Journal |
issn | 2227-9059 |
language | English |
last_indexed | 2024-03-10T15:18:07Z |
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spelling | doaj.art-b5d25e69ae8f4b0f943437fe559a091c2023-11-20T18:44:11ZengMDPI AGBiomedicines2227-90592020-10-0181145310.3390/biomedicines8110453Luteolin Induces Selective Cell Death of Human Pluripotent Stem CellsYoung-Hyun Go0Jumee Kim1Ho-Chang Jeong2Seong-Min Kim3Yun-Jeong Kim4Soon-Jung Park5Sung-Hwan Moon6Hyuk-Jin Cha7Department of Life Science, Sogang University, Seoul 04107, KoreaCollege of Pharmacy, Seoul National University, Seoul 08826, KoreaDepartment of Life Science, Sogang University, Seoul 04107, KoreaCollege of Pharmacy, Seoul National University, Seoul 08826, KoreaCollege of Pharmacy, Seoul National University, Seoul 08826, KoreaStem Cell Research Institute, T&R Biofab Co., Ltd., Siheung 15073, KoreaStem Cell Research Institute, T&R Biofab Co., Ltd., Siheung 15073, KoreaCollege of Pharmacy, Seoul National University, Seoul 08826, KoreaDespite recent advances in clinical stem cell therapy applications based on human pluripotent stem cells (hPSCs), potential teratoma formation due to the presence of residual undifferentiated hPSCs remains a serious risk factor that challenges widespread clinical application. To overcome this risk, a variety of approaches have been developed to eliminate the remaining undifferentiated hPSCs via selective cell death induction. Our study seeks to identify natural flavonoids that are more potent than quercetin (QC), to selectively induce hPSC death. Upon screening in-house flavonoids, luteolin (LUT) is found to be more potent than QC to eliminate hPSCs in a p53-dependent manner, but not hPSC-derived smooth muscle cells or perivascular progenitor cells. Particularly, treating human embryonic stem cell (hESC)-derived cardiomyocytes with LUT efficiently eliminates the residual hESCs and only results in marginal effects on cardiomyocyte (CM) functions, as determined by calcium influx. Considering the technical limitations of isolating CMs due to a lack of exclusive surface markers at the end of differentiation, LUT treatment is a promising approach to minimize teratoma formation risk.https://www.mdpi.com/2227-9059/8/11/453flavonoidquercetinteratomaluteolinhuman pluripotent stem cells |
spellingShingle | Young-Hyun Go Jumee Kim Ho-Chang Jeong Seong-Min Kim Yun-Jeong Kim Soon-Jung Park Sung-Hwan Moon Hyuk-Jin Cha Luteolin Induces Selective Cell Death of Human Pluripotent Stem Cells Biomedicines flavonoid quercetin teratoma luteolin human pluripotent stem cells |
title | Luteolin Induces Selective Cell Death of Human Pluripotent Stem Cells |
title_full | Luteolin Induces Selective Cell Death of Human Pluripotent Stem Cells |
title_fullStr | Luteolin Induces Selective Cell Death of Human Pluripotent Stem Cells |
title_full_unstemmed | Luteolin Induces Selective Cell Death of Human Pluripotent Stem Cells |
title_short | Luteolin Induces Selective Cell Death of Human Pluripotent Stem Cells |
title_sort | luteolin induces selective cell death of human pluripotent stem cells |
topic | flavonoid quercetin teratoma luteolin human pluripotent stem cells |
url | https://www.mdpi.com/2227-9059/8/11/453 |
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