MSC-based VEGF gene therapy in rat myocardial infarction model using facial amphipathic bile acid-conjugated polyethyleneimine

Title
MSC-based VEGF gene therapy in rat myocardial infarction model using facial amphipathic bile acid-conjugated polyethyleneimine
Authors
문형호주민경목혜정이민형황기철김성완정지훈최동훈김선화
Keywords
Facial amphipathic bile acid; Mesenchymal stem cells; Cell-based gene therapy; Vascular endothelial growth factor; Myocardial infarction
Issue Date
2014-02
Publisher
Biomaterials
Citation
VOL 35, NO 5, 1744-1754
Abstract
Mesenchymal stem cells (MSCs) have attracted much attention in regenerative medicine owing to their apparent usefulness as multi-potent replacement cells. The potential of MSC therapy can be further improved by transforming MSCs with therapeutic genes that maximize the efficacy of gene therapy and their own therapeutic ability. Since most conventional transfection methodologies have shown marginal success in delivering exogenous genes into primary cultured cells, efficient gene transfer into primary MSCs is a prerequisite for the development of MSC-based gene therapy strategies to achieve repair and regeneration of damaged tissues. Herein, facially amphipathic bile acid-modified polyethyleneimine (BAPEI) conjugates were synthesized and used to transfer hypoxia-inducible vascular endothelial growth factor gene (pHI-VEGF) in MSCs for the treatment of rat myocardial infarction. Under the optimized transfection conditions, the BA-PEI conjugates significantly increased the VEGF protein expression levels in rat MSCs, compared with traditional transfection methods such as Lipofectamine and branched-PEI (25 kDa). Furthermore, the prepared pHI-VEGF-engineered MSCs (VEGF-MSCs) resulted in improved cell viability, particularly during severe hypoxic exposure in vitro. The transplantation of MSCs genetically modified to overexpress VEGF by BA-PEI enhanced the capillary formation in the infarction region and eventually attenuated left ventricular remodeling after myocardial infarction in rats. This study demonstrates the applicability of the BA-PEI conjugates for the efficient transfection of therapeutic genes into MSCs and the feasibility of using the genetically engineered MSCs in regenerative medicine for myocardial infarction.
URI
http://pubs.kist.re.kr/handle/201004/48685
ISSN
01429612
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KIST Publication > Article
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