Angiogenesis-like Activity of Endothelial Cells Co-cultured with VEGF-producing Smooth Muscle Cells

TitleAngiogenesis-like Activity of Endothelial Cells Co-cultured with VEGF-producing Smooth Muscle Cells
Publication TypeJournal Article
Year of Publication2006
AuthorsElbjeirami, WM, West, JL
JournalTissue Engineering
Volume12
Issue2
Pagination381 - 390
Date Published02/2006
ISSN1557-8690
Keywordsendothelial cell; smooth muscle cells; VEGF; viral transduction
Abstract

A number of strategies have been investigated to improve therapeutic vascularization of ischemic and bioengineered tissues. In these studies, we genetically modified vascular smooth muscle cells (VSMC) to promote endothelial cell proliferation, migration, and formation of microvascular networks. VSMCs were virally transduced to produce vascular endothelial growth factor (VEGF), which acts as a chemoattractant and mitogen of endothelial cells (EC). VSMCs transduced with VEGF(165) cDNA produced significant levels of the protein (2-4 ng/10(5) cell/day). The proliferation of ECs increased after exposure to VEGF-transfected SMCs or their conditioned media. The chemotactic response of ECs to the VEGF-producing cells was explored in two in vitro systems, the modified Boyden chamber assay and a 2-D fence-style migration assay, and both demonstrated increased migration of ECs in response to VEGF-transfected cells. Furthermore, endothelial cells seeded on top of the VEGF-transfected SMCs formed capillary-like structures. These results suggest that VSMCs genetically modified to produce VEGF could be a potential delivery mechanism to enhance endothelial cell migration and subsequent capillary formation, which in turn could improve vascularization of ischemic or regenerating tissue. Furthermore, this system could potentially be used as an in vitro test bed for evaluation of novel angiogenic and anti-angiogenic compounds.

DOI10.1089/ten.2006.12.381
Short TitleTissue Eng
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