Hsp20-engineered mesenchymal stem cells are resistant to oxidative stress via enhanced activation of Akt and increased secretion of growth factors.
Hsp20-engineered mesenchymal stem cells are resistant to oxidative stress via enhanced activation of Akt and increased secretion of growth factors.
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DOI：
10.1002/stem.230
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发表时间：
2009-12
期刊：
影响因子：
5.2
通讯作者：
Fan, Guo-Chang
中科院分区：
文献类型：
--
作者：
Wang, Xiaohong;Zhao, Tiemin;Huang, Wei;Wang, Tao;Qian, Jiang;Xu, Meifeng;Kranias, Evangelia G.;Wang, Yigang;Fan, Guo-Chang
关键词：
尽管热休克预处理已被证明可促进细胞在氧化应激下的存活，但不同细胞的热休克反应性质是多变且复杂的。因此，尚不清楚用单个热休克蛋白（Hsp）基因修饰的间充质干细胞（MSCs）在修复受损心脏方面是否有效。在本研究中，我们用Hsp20基因对大鼠间充质干细胞进行基因工程改造（Hsp20 - MSCs），并通过心内注射在大鼠左前降支结扎（LAD）模型中检测细胞存活、血管再生和功能改善情况。我们观察到，在体外，Hsp20的过表达可保护间充质干细胞免受氧化应激引发的细胞死亡。在移植到梗死心脏后第4天，与载体 - MSCs相比，Hsp20 - MSCs的存活率提高了约两倍。此外，与载体 - MSCs相比，Hsp20 - MSCs改善了梗死心肌的心脏功能，同时伴有纤维化减少和血管密度增加。Hsp20产生有益作用的机制与Akt激活增强以及生长因子（血管内皮生长因子、成纤维细胞生长因子 - 2和胰岛素样生长因子 - 1）分泌增加有关。通过将成年大鼠心肌细胞与来自Hsp20 - MSCs的应激条件培养基共培养，在体外进一步验证了Hsp20 - MSCs的旁分泌作用。综上所述，这些数据支持在移植前对间充质干细胞进行基因修饰可能有利于治疗心肌梗死这一前提。
Although heat-shock preconditioning has been shown to promote cell survival under oxidative stress, the nature of heat-shock response from different cells is variable and complex. Therefore, it remains unclear whether mesenchymal stem cells (MSCs) modified with a single heat-shock protein (Hsp) gene are effective in the repair of a damaged heart. In this study, we genetically engineered rat MSCs with Hsp20 gene (Hsp20-MSCs) and examined cell survival, revascularization, and functional improvement in rat left anterior descending ligation (LAD) model via intracardial injection. We observed that overexpression of Hsp20 protected MSCs against cell death triggered by oxidative stress in vitro. The survival of Hsp20-MSCs was increased by approximately twofold by day 4 after transplantation into the infarcted heart, compared with that of vector-MSCs. Furthermore, Hsp20-MSCs improved cardiac function of infarcted myocardium as compared with vector-MSCs, accompanied by reduction of fibrosis and increase in the vascular density. The mechanisms contributing to the beneficial effects of Hsp20 were associated with enhanced Akt activation and increased secretion of growth factors (VEGF, FGF-2, and IGF-1). The paracrine action of Hsp20-MSCs was further validated in vitro by cocultured adult rat cardiomyocytes with a stress-conditioned medium from Hsp20-MSCs. Taken together, these data support the premise that genetic modification of MSCs before transplantation could be salutary for treating myocardial infarction.
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影响因子：
20.1
作者：
Fan GC;Zhou X;Wang X;Song G;Qian J;Nicolaou P;Chen G;Ren X;Kranias EG
通讯作者：
Kranias EG
影响因子：
5
作者：
Dai, Ying;Ashraf, Muhammad;Xu, Meifeng
通讯作者：
Xu, Meifeng
影响因子：
20.1
作者：
Fan, GC;Chu, GX;Kranias, EG
通讯作者：
Kranias, EG
DOI：
10.1073/pnas.0610024104
发表时间：
2007-01-30
影响因子：
11.1
作者：
Mirotsou, Maria;Zhang, Zhongyan;Dzau, Victor
通讯作者：
Dzau, Victor
影响因子：
4.8
作者：
Gnecchi, Massimiliano;He, Huamei;Dzau, Victor J.
通讯作者：
Dzau, Victor J.