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

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.