Paracrine action of HO-1-modified mesenchymal stem cells mediates cardiac protection and functional improvement
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- 作者：Bin Zeng ; Xiaofeng Ren ; Guosheng Lin ; Chengang Zhu ; Honglei Chen ; Jiechao Yin ; Hong Jiang ; Bo Yang ; Danhua Ding
- 关键词：Mesenchymal stem cells ; Human heme oxygenase-1 ; Gene therapy ; Myocardial cell injury
- 刊名：Cell Biology International
- 出版年：2008
- 出版时间：October 2008
- 年：2008
- 卷：32
- 期：10
- 页码：1256-1264
- 全文大小：488 K
文摘
The aim has been to determine whether the supernatants of mesenchymal stem cells (MSCs) transfected with adenovirus carrying human heme oxygenase-1 (hHO-1) gene protect cardiomyocytes from ischemic injury. We have found that hHO-1 infected MSCs (hHO-1-MSCs) increased expression of hHO-1 protein. Apoptosis of cultured hHO-1-MSCs exposed to hypoxia was suppressed. Several cytokines, including HGF, bFGF, TGF-β, VEGF and IL-1β, were produced by hHO-1-MSCs, some being significantly enhanced under hypoxia stimulation. Meanwhile, those cytokines reduced caspase-3 level and activity in cultured adult rat ventricular cardiomyocytes (ARVCs) exposed to hypoxia. Supernatants obtained from hHO-1-MSCs improved left ventricular function, limited myocardial infarct size, increased microvessel density, and inhibited apoptosis of cardiomyocytes in rat myocardial infarction. It can be concluded hHO-1-modified MSCs prevent myocardial cell injury via secretion of paracrine-acting mediators.