Journal
BIOMATERIALS
Volume 29, Issue 13, Pages 2125-2137Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2008.01.014
Keywords
liposome; VEGF(165); skeletal myoblast; cardiac repair
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We aim to investigate the feasibility and efficacy of cholesterol (Chol) + DOTAP liposome (CD liposome) based human vascular endothelial growth factor-165 (hVEGF(165)) gene transfer into human skeletal myoblasts (hSkM) for cardiac repair. The feasibility and efficacy of CD liposome for gene transfer with hSkM was characterized using plasmid carrying enhanced green fluorescent protein (pEGFP). Based on the optimized transfection procedure, hSkM were transfected with CD lipoplexes carrying plasmid-hVEGF(165) (CD-phVEGF(165)). The genetically modified hSkM were transplanted into rat heart model of acute myocardial infarction. Flow cytometry revealed that about 7.99% hSkM could be transfected with pEGFP. Based on the optimized transfection condition, transfected hSkM expressed hVEGF(165) up to day-18 (1.7 +/- 0.1 ng/ml) with peak at day-2 (13.1 +/- 0.52 ng/ml) with > 85% cell viability. Animal studies revealed that reduced apoptosis, improved angiogenesis with blood flow in group-3 animal's heart were achieved as compared to group-1 and 2. Ejection fraction was best recovered in group-3 animals. The study demonstrates that though gene transfection efficiency using CD liposome mediated hVEGF(165) gene transfer with hSkM was low; hVEGF(165) gene expression efficiency was sufficient to induce neovascularization, improve blood flow and injured heart function. (c) 2008 Elsevier Ltd. All rights reserved.
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