Open AccessSirtuin3 protects aged human mesenchymal stem cells against oxidative stress and enhances efficacy of cell therapy for ischaemic heart diseases
Author(s) -
Zhang DongYang,
Zhang ChunFeng,
Fu BiCheng,
Sun Lu,
Wang XueQing,
Chen Wei,
Liu Wei,
Liu KaiYu,
Du GuoQing,
Ma ChongYi,
Jiang ShuLin,
Li RenKe,
Tian Hai
Publication year - 2018
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.13821
Subject(s) - oxidative stress , sirt3 , mesenchymal stem cell , transplantation , superoxide dismutase , antioxidant , stem cell , catalase , cell therapy , stem cell therapy , cancer research , viability assay , transfection , medicine , pharmacology , cell , chemistry , biology , microbiology and biotechnology , endocrinology , biochemistry , enzyme , sirtuin , gene , nad+ kinase
Sirtuin3 (SIRT3) is associated with oxidative stress and lifespan. However, the possible mechanisms underlying its influence are unknown. We hypothesized that SIRT 3 increases the antioxidant capacity of aged cells and improves the efficacy of human mesenchymal stem cell (hMSC) therapy for ischaemic heart diseases in aged patients. In vitro, the antioxidant capacity of old hMSC s (O‐ hMSC s) was increased after SIRT 3 overexpression using a gene transfection technique, while the antioxidant capacity of young hMSC s (Y‐ hMSC s) was decreased by SIRT 3 silencing. The levels of forkhead box O3a (FoxO3a) in the nucleus, and antioxidant enzymes Mn‐superoxide dismutase (Mn SOD ) and catalase (CAT) increased in SIRT 3‐overexpressed O‐ hMSC s while they decreased in SIRT 3‐silenced Y‐ hMSC s after oxidative stress. Following myocardial infarction in adult rats in vivo, infarct size decreased and cardiac function was significantly enhanced after cell transplantation with SIRT 3 overexpressed O‐ hMSC s. The number of apoptotic cells decreased and the survival rate of transplanted cells increased following SIRT 3 overexpression in O‐ hMSC s. SIRT 3 protects aged hMSC s against oxidative stress by positively regulating antioxidant enzymes (Mn SOD and CAT ) via increasing the expression of FoxO3a in the nucleus. The efficacy of aged hMSC transplantation therapy for ischaemic heart diseases can be improved by SIRT3 overexpression.