Journal
FASEB JOURNAL
Volume 21, Issue 14, Pages 3896-3903Publisher
FEDERATION AMER SOC EXP BIOL
DOI: 10.1096/fj.06-7873com
Keywords
tissue engineering; in vitro models; angiogenesis
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Funding
- NHLBI NIH HHS [R01 HL-069957] Funding Source: Medline
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Growth factors have been widely used in strategies to regenerate and repair diseased tissues, but current therapies that go directly from bench to bedside have had limited clinical success. We hypothesize that engineering successful therapies with recombinant proteins will often require specific quantitative information of the spatiotemporal role of the factors and the development of sophisticated delivery approaches that provide appropriate tissue exposures. This hypothesis was tested in the context of therapeutic angiogenesis. An in vitro model of angiogenesis was adapted to quantify the role of the concentration/ gradient of vascular endothelial growth factor [VEGF( 165)] on microvascular endothelial cells, and a delivery system was then designed, based on a mathematical model, to provide the desired profile in ischemic mice hindlimbs. This system significantly enhanced blood vessel formation, and perfusion and recovery from severe ischemia. This general approach may be broadly applicable to growth factor therapies.
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