The influence of combined trophic factors on the success of fetal pancreasgrafts

Background, Fetal pancreas (FP) has the capacity for abundant proliferation and beta cell differentiation. Insulin-like growth factor-1 (IGF-1) promot es FP engraftment in the i,m. site and reversal of diabetes in a rodent mod el. However, reversal of diabetes by an FP transplant in rats under the inf luence of IGF-1 is still an inefficient process requiring multiple FP graft s and a prolonged latent period, Numerous other growth and differentiation factors, which include platelet derived growth factor (PDGF), vascular endo thelial growth factor, endothelial cell growth factor-alpha and pancreatic islet neogenesis-associated protein, have been implicated in beta cell neog enesis and proliferation. We have analyzed the in vivo role of these growth factors in FP engraftment and reversal of streptozotocin-induced diabetes in rats. Methods, IGF-1 alone or in combination with other trophic factors was local ly administered to eight FP isografts in the thigh muscle of diabetic rats. Results. Diabetes was reversed in a mean of 60+/-26 days in 11 of 11 animal s treated with IGF-1. PDGF alone did not promote reversal of diabetes; howe ver, PDGF + IGF-1 resulted in euglycemia in 6 of 6, with a mean of 36+/-14 days (P<0.05), Islet neogenesis-associated protein +IGF-1 resulted in rever sal of diabetes in 6 of 6 rats with a mean interval of 50+/-10 days. Vascul ar endothelial growth factor or endothelial cell growth factor-alpha + IGF- 1 provided no advantage compared with IGF-1 alone. Conclusions. These results demonstrate that IGF-1 is a potent trophic facto r for transplanted FP and that PDGF acts synergistically with IGF-1 to prom ote reversal of diabetes by transplanting FP.