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Journal of Cardiovascular Translational Research

Published in:

01-03-2009

AAV-2-Mediated Expression of IGF-1 in Skeletal Myoblasts Stimulates Angiogenesis and Cell Survival

Authors: Indira V. Subramanian, Brian C. A. Fernandes, Timothy Robinson, Jennifer Koening, Kelly S. LaPara, S. Ramakrishnan

Published in: Journal of Cardiovascular Translational Research | Issue 1/2009

Abstract

The transplantation of skeletal myoblasts is being tested in various organ systems to facilitate tissue repair and regeneration. Previous studies have indicated that transplanted cells for varied reasons were not surviving in sufficient numbers following transplantation, thus negatively affecting overall therapeutic efficacy of the approach. We hypothesize that the genetic modification of myoblasts to express insulin-like growth factor 1 (IGF-1) locally may enhance the survival of transplanted cells by stimulating neo-vascularization, decreasing apoptosis, and promoting cell proliferation. Using an adeno-associated virus (adeno-associated virus type 2) vector system, the IGF-1 gene was introduced into canine skeletal myoblasts. As a negative control, myoblasts transduced with the green fluorescence protein (GFP) was used. Relative angiogenic response induced by IGF-1 myoblast was compared to VEGF165-induced neo-vascularization using Matrigel plugs under similar conditions. In vitro evaluation and characterization revealed that the secreted IGF-1 protein was biologically and functionally active in promoting endothelial cell proliferation, migration and assembly into vessel-like structures. Matrigel plugs containing the three test groups were implanted subcutaneously in nude mice (n = 5). After 3 weeks, analysis of explanted samples revealed an enhanced neo-vascularization with an average microvessel density per field for IGF-1 at 55.9 versus 33.4 for vascular endothelial growth factor and 24 for GFP. Additionally, apoptosis was significantly reduced (p ≤ 0.02) and proliferative capacity of implanted cells significantly increased (p ≤ 0.01) with the IGF-1-transduced myoblasts. We conclude that the genetic modification of skeletal myoblasts with the IGF-1 gene offers a potential means for enhanced cell survival following transplantation.

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Title: AAV-2-Mediated Expression of IGF-1 in Skeletal Myoblasts Stimulates Angiogenesis and Cell Survival
Authors: Indira V. Subramanian
Brian C. A. Fernandes
Timothy Robinson
Jennifer Koening
Kelly S. LaPara
S. Ramakrishnan
Publication date: 01-03-2009
Publisher: Springer US
Published in: Journal of Cardiovascular Translational Research / Issue 1/2009
Print ISSN: 1937-5387
Electronic ISSN: 1937-5395
DOI: https://doi.org/10.1007/s12265-008-9063-8

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AAV-2-Mediated Expression of IGF-1 in Skeletal Myoblasts Stimulates Angiogenesis and Cell Survival

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