FGF-1 delivery from multilayer alginate microbeads stimulates a rapid and persistent increase in vascular density

Microvasc Res. 2013 Nov:90:23-9. doi: 10.1016/j.mvr.2013.08.006. Epub 2013 Aug 23.

Abstract

In recent years, great advances have been made in the use of islet transplantation as a treatment for type I diabetes. Indeed, it is possible that stimulation of local neovascularization upon transplantation could improve functional graft outcomes. In the present study, we investigate the use of multilayered alginate microbeads to provide a sustained delivery of FGF-1, and whether this results in increased neovascularization in vivo. Multilayered alginate microbeads, loaded with either 150ng or 600ng of FGF-1 in the outer layer, were surgically implanted into rats using an omentum pouch model and compared to empty microbead implants. Rats were sacrificed at 4days, 1week, and 6weeks. Staining for CD31 showed that both conditions of FGF-1 loaded microbeads resulted in a significantly higher vessel density at all time points studied. Moreover, at 6weeks, alginate microbeads containing 600ng FGF-1 provided a greater vascular density compared to both the control group and the microbeads loaded with 150ng FGF-1. Omenta analyzed via staining for smooth muscle alpha actin showed no variation in mural cell density at either 4days or 1week. At 6weeks, however, omenta exposed to microbeads loaded with 600ng FGF-1 showed an increase in mural cell staining compared to controls. These results suggest that the sustained delivery of FGF-1 from multilayered alginate microbeads results in a rapid and persistent vascular response. An increase in the local blood supply could reduce the number of islets required for transplantation in order to achieve clinical efficacy.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism
  • Alginates / chemistry*
  • Angiogenesis Inducing Agents / administration & dosage
  • Angiogenesis Inducing Agents / chemistry
  • Angiogenesis Inducing Agents / pharmacology*
  • Animals
  • Biomarkers / metabolism
  • Delayed-Action Preparations
  • Drug Carriers*
  • Endothelial Cells / drug effects
  • Endothelial Cells / metabolism
  • Fibroblast Growth Factor 1 / administration & dosage
  • Fibroblast Growth Factor 1 / chemistry
  • Fibroblast Growth Factor 1 / pharmacology*
  • Glucuronic Acid / chemistry
  • Hexuronic Acids / chemistry
  • Muscle, Smooth, Vascular / drug effects
  • Muscle, Smooth, Vascular / metabolism
  • Myocytes, Smooth Muscle / drug effects
  • Myocytes, Smooth Muscle / metabolism
  • Neovascularization, Physiologic / drug effects*
  • Omentum / blood supply*
  • Platelet Endothelial Cell Adhesion Molecule-1 / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Time Factors

Substances

  • Actins
  • Alginates
  • Angiogenesis Inducing Agents
  • Biomarkers
  • Delayed-Action Preparations
  • Drug Carriers
  • Hexuronic Acids
  • Platelet Endothelial Cell Adhesion Molecule-1
  • smooth muscle actin, rat
  • Fibroblast Growth Factor 1
  • Glucuronic Acid