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

Quan,Zhe; Wang,Qiang-Li; Zhou,Pei; Wang,Guo-Dong; Tan,Yu-Zhen; Wang,Hai-Jie

doi:10.3892/ijmm.2017.2950

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

Authors:
- Zhe Quan
- Qiang-Li Wang
- Pei Zhou
- Guo-Dong Wang
- Yu-Zhen Tan
- Hai-Jie Wang
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Affiliations: Department of Anatomy, Histology and Embryology, Shanghai Medical School, Fudan University, Shanghai 200032, P.R. China, School of Basic Medical Sciences, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, P.R. China
Published online on: April 11, 2017 https://doi.org/10.3892/ijmm.2017.2950
Pages: 1347-1356
Copyright: © Quan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The survival of transplanted stem cells in ischemic tissue is poor. In the present study, the effects of thymosin β4 (Tβ4) on the survival and angiogenesis of endothelial progenitor cells (EPCs) and improvement in cardiac functions after transplantation of Tβ4-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 Tβ4 at different concentrations (0.05, 0.1 and 0.2 µM), 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 Tβ4 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 Tβ4-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. Tβ4 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, Tβ4 increased p-Akt expression in the cells. The cytoprotective and proangiogenic effects of Tβ4 were in a dose-dependent manner. Tβ4-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 Tβ4 is a novel strategy for the repair of ischemic tissue after transplantation in MI.

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