Thymosin β4 promotes the survival and angiogenesis of transplanted endothelial progenitor cells in the infarcted myocardium

The survival of transplanted stem cells in ischemic tissue is poor. In the present study, the effects of thymosin beta 4 (T beta 4) on the survival and angiogenesis of endothelial progenitor cells (EPCs) and improvement in cardiac functions after transplantation of T beta 4-treated EPCs in the infarcted myocardium were investigated. EPCs were isolated from bone marrow of adult male rats and incubated in Endothelial Basal Medium-2. Then the cells were treated with T beta 4 at different concentrations (0.05, 0.1 and 0.2 mu M), and cells incubated with DMEM were set as controls. MTT assay, Transwell assay and tube formation in Matrigel were used to detect cell viability, migration and angiogenesis, respectively. For examining the protective effect of T beta 4 on EPCs, the cells were also incubated in the condition of hypoxia and serum deprivation. p-Akt expression was also examined using western blot analysis. Rat models of myocardial infarction (MI) were established by ligation of the anterior descending branch of the left coronary artery. At four weeks after intramyocardial injection of T beta 4-treated EPCs, the changes in cardiac functions, size of the scar tissue and density of microvessels were examined by echocardiography, Masson's trichrome staining, immunohistochemistry and fluorescence in situ hybridization (FISH) for the Y-chromosome. T beta 4 enhanced EPC viability, protected the cells from apoptosis in hypoxia and serum deprivation, and promoted the proliferation and migration of the cells and formation of capillary-like structures in the cells. Moreover, T beta 4 increased p-Akt expression in the cells. The cytoprotective and proangiogenic effects of T beta 4 were in a dose-dependent manner. T beta 4-treated EPCs improved cardiac function, enhanced the repair of the infarcted myocardium, and promoted angiogenesis after transplantation in the infarcted myocardium. In conclusion, pretreatment of EPCs with T beta 4 is a novel strategy for the repair of ischemic tissue after transplantation in MI.