The influence of combined trophic factors on the success of fetal pancreas grafts
| Autor: | D M, Desai, G A, Adams, X, Wang, E J, Alfrey, R K, Sibley, D C, Dafoe |
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| Rok vydání: | 1999 |
| Předmět: |
Blood Glucose
Platelet-Derived Growth Factor Vascular Endothelial Growth Factor A Lymphokines Vascular Endothelial Growth Factors Graft Survival Proteins Drug Synergism Pancreatitis-Associated Proteins Endothelial Growth Factors Diabetes Mellitus Experimental Rats Transplantation Isogeneic Antigens Neoplasm Fetal Tissue Transplantation Rats Inbred Lew Biomarkers Tumor Animals Lectins C-Type Pancreas Transplantation Insulin-Like Growth Factor I Growth Substances |
| Zdroj: | Transplantation. 68(4) |
| ISSN: | 0041-1337 |
| Popis: | Fetal pancreas (FP) has the capacity for abundant proliferation and beta cell differentiation. Insulin-like growth factor-1 (IGF-1) promotes FP engraftment in the i.m. site and reversal of diabetes in a rodent model. However, reversal of diabetes by an FP transplant in rats under the influence of IGF-1 is still an inefficient process requiring multiple FP grafts and a prolonged latent period. Numerous other growth and differentiation factors, which include platelet derived growth factor (PDGF), vascular endothelial growth factor, endothelial cell growth factor-alpha and pancreatic islet neogenesis-associated protein, have been implicated in beta cell neogenesis and proliferation. We have analyzed the in vivo role of these growth factors in FP engraftment and reversal of streptozotocin-induced diabetes in rats.IGF-1 alone or in combination with other trophic factors was locally administered to eight FP isografts in the thigh muscle of diabetic rats.Diabetes was reversed in a mean of 60+/-26 days in 11 of 11 animals treated with IGF-1. PDGF alone did not promote reversal of diabetes; however, PDGF + IGF-1 resulted in euglycemia in 6 of 6, with a mean of 36+/-14 days (P0.05). Islet neogenesis-associated protein +IGF-1 resulted in reversal of diabetes in 6 of 6 rats with a mean interval of 50+/-10 days. Vascular endothelial growth factor or endothelial cell growth factor-alpha + IGF-1 provided no advantage compared with IGF-1 alone.These results demonstrate that IGF-1 is a potent trophic factor for transplanted FP and that PDGF acts synergistically with IGF-1 to promote reversal of diabetes by transplanting FP. |
| Databáze: | OpenAIRE |
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