Angiogenesis Using Recombinant Basic Fibroblast Growth Factor With Atelocollagen in Normal and Hind Limb Ischemia Models

Abstract

Background: Basic fibroblast growth factor (bFGF) is an angiogenic factor with a short half-life. Because recombinant bFGF is in clinical use, we hypothesized that the localization of recombinant bFGF with atelocollagen would have angiogenic effects at the injection site in normal and hind limb ischemic animal models.

Methods and Results: We administered the recombinant bFGF with atelocollagen intramuscularly to hind limbs in normal rabbits or in a mouse model of femoral artery ligation to explore the pharmacological action for ischemia. We evaluated blood flow in the ischemic/normal limb using laser speckle perfusion imaging and the density of blood vessels by pathological examination. At the administration site in normal rabbits, a significant increase in the number of blood vessels was noted at 14 days post-administration of recombinant bFGF with atelocollagen compared with saline or atelocollagen alone. In mice with femoral artery ligation, blood flow and vessels in the ischemic hind limb increased at 2 weeks after injection and more at 4 weeks after injection, and the effect was most significant in mice administered 100 μg of recombinant bFGF with 3% of atelocollagen.

Conclusions: Intramuscular administration of recombinant bFGF with atelocollagen induced angiogenesis between 2 and 4 weeks in both normal and ischemic hind limbs.