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Different effects of resveratrol on early and late passage mesenchymal stem cells through β-catenin regulation

 Dong Suk Yoon  ;  Yoorim Choi  ;  Seong Mi Choi  ;  Kwang Hwan Park  ;  Jin Woo Lee 
 Biochemical and Biophysical Research Communications, Vol.467(4) : 1026-1032, 2015 
Journal Title
 Biochemical and Biophysical Research Communications 
Issue Date
Adult ; Cellular Senescence/drug effects ; Humans ; Mesenchymal Stromal Cells/drug effects* ; Mesenchymal Stromal Cells/metabolism ; Stilbenes/pharmacology* ; beta Catenin/metabolism*
Cellular senescence ; Mesenchymal stem cells ; Resveratrol ; SIRT1 ; β-catenin
Resveratrol is a sirtuin 1 (SIRT1) activator and can function as an anti-inflammatory and antioxidant factor. In mesenchymal stem cells (MSCs), resveratrol enhances the proliferation and differentiation potential and has an anti-aging effect. However, contradictory effects of resveratrol on MSC cultures have been reported. In this study, we found that resveratrol had different effects on MSC cultures according to their cell passage and SIRT1 expression. Resveratrol enhanced the self-renewal potential and multipotency of early passage MSCs, but accelerated cellular senescence of late passage MSCs. In early passage MSCs expressing SIRT1, resveratrol decreased ERK and GSK-3β phosphorylation, suppressing β-catenin activity. In contrast, in late passage MSCs, which did not express SIRT1, resveratrol increased ERK and GSK-3β phosphorylation, activating β-catenin. We confirmed that SIRT1-deficient early passage MSCs treated with resveratrol lost their self-renewal potential and multipotency, and became senescent due to increased β-catenin activity. Sustained treatment with resveratrol at early passages maintained the self-renewal potential and multipotency of MSCs up to passage 10. Our findings suggest that resveratrol can be effectively applied to early passage MSC cultures, whereas parameters such as cell passage and SIRT1 expression must be taken into consideration before applying resveratrol to late passage MSCs.
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1. College of Medicine (의과대학) > Dept. of Orthopedic Surgery (정형외과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
Yonsei Authors
Park, Kwang Hwan(박광환) ORCID logo https://orcid.org/0000-0002-2110-0559
Yoon, Dong Suk(윤동석)
Lee, Jin Woo(이진우) ORCID logo https://orcid.org/0000-0002-0293-9017
Choi, Yoo Rim(최유림)
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