Paracrine action of HO‐1‐modified mesenchymal stem cells mediates cardiac protection and functional improvement

作者：Bin Zeng, Xiaofeng Ren, Guosheng Lin, Chengang Zhu, Honglei Chen, Jiechao Yin, Hong Jiang, Bo Yang, Danhua Ding · 发表于：Cell Biology International · 年份：2008 · DOI：10.1016/j.cellbi.2008.07.010 · 被引用次数：47 · 研究领域：Mesenchymal stem cell research、Heme Oxygenase-1 and Carbon Monoxide、Cardiac Arrest and Resuscitation

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-beta, VEGF and IL-1beta, 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.