AAV-2-mediated expression of IGF-1 in skeletal myoblasts stimulates angiogenesis and cell survival

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

Research output: Contribution to journalArticle

5 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)81-92
Number of pages12
JournalJournal of Cardiovascular Translational Research
Volume2
Issue number1
DOIs
StatePublished - Jan 1 2009
Externally publishedYes

Fingerprint

Skeletal Myoblasts
Somatomedins
Cell Survival
Myoblasts
Dependovirus
Transplantation
Fluorescence
Cell Proliferation
Apoptosis
Proteins
Microvessels
Nude Mice
Vascular Endothelial Growth Factor A
Genes
Cell Movement
Canidae
Regeneration
Endothelial Cells

Keywords

  • AAV-2
  • Angiogenesis
  • IGF-1
  • Myoblasts

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Pharmaceutical Science
  • Cardiology and Cardiovascular Medicine
  • Genetics(clinical)

Cite this

AAV-2-mediated expression of IGF-1 in skeletal myoblasts stimulates angiogenesis and cell survival. / Subramanian, Indira V.; Fernandes, Brian C.A.; Robinson, Timothy; Koening, Jennifer; LaPara, Kelly S.; Ramakrishnan, Sundaram.

In: Journal of Cardiovascular Translational Research, Vol. 2, No. 1, 01.01.2009, p. 81-92.

Research output: Contribution to journalArticle

Subramanian, Indira V. ; Fernandes, Brian C.A. ; Robinson, Timothy ; Koening, Jennifer ; LaPara, Kelly S. ; Ramakrishnan, Sundaram. / AAV-2-mediated expression of IGF-1 in skeletal myoblasts stimulates angiogenesis and cell survival. In: Journal of Cardiovascular Translational Research. 2009 ; Vol. 2, No. 1. pp. 81-92.
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