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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Main Authors: Young-Hyun Go, Jumee Kim, Ho-Chang Jeong, Seong-Min Kim, Yun-Jeong Kim, Soon-Jung Park, Sung-Hwan Moon, Hyuk-Jin Cha
Format: Article
Language:English
Published: MDPI AG 2020-10-01
Series:Biomedicines
Subjects:
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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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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