The influence of combined trophic factors on the success of fetal pancreas grafts.
BACKGROUND
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.


METHODS
IGF-1 alone or in combination with other trophic factors was locally 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 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 (P<0.05). 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.


CONCLUSIONS
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.
Desai
D M
DM
Department of Surgery, Stanford University School of Medicine, CA 94305, USA.
Adams
G A
GA
Wang
X
X
Alfrey
E J
EJ
Sibley
R K
RK
Dafoe
D C
DC
D000818:Animals; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D001786:Blood Glucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000601:surgery; D004357:Drug Synergism; D016228:Endothelial Growth Factors / Q000008:administration & dosage; D016332:Fetal Tissue Transplantation / Q000502:physiology*; D006085:Graft Survival; D006133:Growth Substances / Q000008:administration & dosage* / Q000502:physiology; D007334:Insulin-Like Growth Factor I / Q000008:administration & dosage; D037181:Lectins, C-Type; D008222:Lymphokines / Q000008:administration & dosage; D016035:Pancreas Transplantation / Q000502:physiology*; D000073718:Pancreatitis-Associated Proteins; D010982:Platelet-Derived Growth Factor / Q000008:administration & dosage; D011506:Proteins / Q000008:administration & dosage; D051381:Rats; D011917:Rats, Inbred Lew; D014185:Transplantation, Isogeneic; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D001786:Blood Glucose; D016228:Endothelial Growth Factors; D006133:Growth Substances; D037181:Lectins, C-Type; D008222:Lymphokines; D000073718:Pancreatitis-Associated Proteins; D010982:Platelet-Derived Growth Factor; D011506:Proteins; C000612141:REG3A protein, human; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D007334:Insulin-Like Growth Factor I