Transplantation of SIRT1-engineered aged mesenchymal stem cells improves cardiac function in a rat myocardial infarction model

被引：36

作者：

Liu, Xianbao ^{[1
,2
]}

Chen, Huiqiang ^{[1
,2
]}

Zhu, Wei ^{[2
]}

Chen, Han ^{[1
,2
]}

Hu, Xinyang ^{[1
,2
]}

Jiang, Zhi ^{[1
,2
]}

Xu, Yinchuan ^{[1
,2
]}

Zhou, Yu ^{[1
,2
]}

Wang, Kan ^{[1
,2
]}

Wang, Lihan ^{[1
,2
]}

Chen, Panpan ^{[1
,2
]}

Hu, Hengxun ^{[1
,2
]}

Wang, Chen ^{[1
,2
]}

Zhang, Na ^{[1
,2
]}

Ma, Qunchao ^{[1
,2
]}

Huang, Mingyuan ^{[1
,2
]}

Hu, Dexing ^{[1
,2
]}

Zhang, Ling ^{[2
]}

Wu, Rongrong ^{[2
]}

Wang, Yaping ^{[1
,2
]}

Xu, Qiyuan ^{[1
,2
]}

Yu, Hong ^{[2
]}

Wang, Jian'an ^{[1
,2
]}

机构：

[1] Zhejiang Univ, Affiliated Hosp 2, Sch Med, Dept Cardiol,Key Div Minist Hlth, Hangzhou 310009, Zhejiang, Peoples R China

[2] Zhejiang Univ, Affiliated Hosp 2, Sch Med, Prov Key Lab Cardiovasc Res, Hangzhou 310009, Zhejiang, Peoples R China

来源：

JOURNAL OF HEART AND LUNG TRANSPLANTATION | 2014年 / 33卷 / 10期

基金：

中国国家自然科学基金;

关键词：

SIRT1; mesenchymal stem cells; aging; myocardial infarction; stem cell therapy; OXIDATIVE STRESS; BONE; DIFFERENTIATION; ACTIVATION; SENESCENCE; SECRETION; RESISTANT; SURVIVAL; DEATH;

D O I：

10.1016/j.healun.2014.05.008

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

BACKGROUND: Previous studies have demonstrated that biological aging has a negative influence on the therapeutic effects of mesenchymal stem cells (MSCs)-based therapy. Using a rat myocardial infarction (MI) model, we tested the hypothesis that silent mating type information regulation 2 homolog 1 (SIRT1) may ameliorate the phenotype and improve the function of aged MSCs and thus enhance the efficacy of aged MSCs-based therapy. METHODS: Sixty female rats underwent left anterior descending coronary artery ligation and were randomly assigned to receiving: intramyocardial injection of cell culture medium (DMEM group); SIRT1 overexpression vector-treated aged MSCs (SIRT1-aged MSCs group) obtained from aged male SD rats or empty vector-treated aged MSCs (vector-aged MSCs group). Another 20 sham-operated rats that underwent open-chest surgery without coronary ligation or any other intervention served as controls. RESULTS: SIRT1-aged MSC group exhibited enhanced blood vessel density in the border zone of MI hearts, which was associated with reduced cardiac remodeling, leading to improved cardiac performance. Consistent with the in vivo data, our in vitro experiments also demonstrated that SIRT1 overexpression ameliorated aged MSCs senescent phenotype and recapitulated the pro-angiogenesis property of MSCs and conferred the anti-stress response capabilities, as indicated by increases in pro-angiogenic factors, angiopoietin 1 (Ang1) and basic fibroblast growth factor (bFGF), expressions and a decrease in anti-angiogenic factor thrombospondin-1 (TBS1) at mRNA levels, and increases in Bcl-2/Bax ratio at protein level. CONCLUSIONS: Up-regulating SIRT1 expression could enhance the efficacy of aged MSCs-based therapy for MI as it relates to the amelioration of senescent phenotype and hence improved biological function of aged MSCs. (C) 2014 International Society for Heart and Lung Transplantation. All rights reserved.

引用

页码：1083 / 1092

页数：10

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