Lentiviral vector-mediated co-overexpression of VEGF and Bcl-2 improves mesenchymal stem cell survival and enhances paracrine effects in vitro

Mesenchymal stem cell (MSC) transplantation has emerged as a promising therapy for ischemic heart disease; however, the low survival rate of transplanted cells limits their therapeutic efficacy. The aim of this study was to investigate whether the dual genetic modification of vascular endothelial gr...

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Bibliographic Details
Published in:International journal of molecular medicine 2017-08, Vol.40 (2), p.418-426
Main Authors: Ni, Xiaobin, Ou, Caiwen, Guo, Jingbin, Liu, Bei, Zhang, Jianwu, Wu, Zhiye, Li, Hekai, Chen, Minsheng
Format: Article
Language:English
Subjects:
Apoptosis
Autophagy
B-cell lymphoma-2
Cardiovascular disease
Cell culture
Deoxyribonucleic acid
DNA
Gene expression
Genes
Genetic aspects
Health aspects
mesenchymal stem cell
paracrine effect
Plasmids
Rodents
Stem cells
Studies
Vascular endothelial growth factor
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Summary:Mesenchymal stem cell (MSC) transplantation has emerged as a promising therapy for ischemic heart disease; however, the low survival rate of transplanted cells limits their therapeutic efficacy. The aim of this study was to investigate whether the dual genetic modification of vascular endothelial growth factor (VEGF) and B-cell lymphoma-2 (Bcl-2) confers a higher expression level of the target genes, better survival and a stronger paracrine effect in MSCs in an adverse environment than the modification of the individual genes. For this purpse, a lentiviral vector was constructed by using a self-cleaving T2A peptide sequence to link and achieve the co-overexpression of VEGF and Bcl-2. Rat MSCs were transfected to obtain cell lines that exhibited a stable overexpression. An in vitro model of oxygen glucose deprivation (OGD) was applied to mimic the ischemic microenvironment, and cell apoptosis, autophagy and the paracrine effects were then determined. Compared with the MSCs in which individual genes were modified and the control MSCs, the MSCs which were subjected to dual genetic modification had a higher expression level of the target genes, a more rapid proliferation, reduced apoptosis, decreased autophagy and an enhanced paracrine effect. Furthermore, the suppression of autophagy was found to contribute to the inhibition of apoptosis in this in vitro OGD model. On the whole, these data indicate that the co-overexpression of VEGF and Bcl-2 protects MSCs in an ischemic environment by inhibiting apoptosis, suppressing autophagy and enhancing the paracrine effects.
ISSN:1107-3756
1791-244X
DOI:10.3892/ijmm.2017.3019