The effect of fibroblast activation on vascularization in transplanted pancreatic islets.
BACKGROUND
Insufficient revascularization of transplanted pancreatic islets is an important reason why the long-term effects of pancreatic islet transplantation on type I diabetes patients have been so limited. The goal of this study was to investigate the role of fibroblasts (FBs) activated by tumor cell supernatants on the vascularization of transplanted pancreatic islets.


METHODS
Pancreatic islets and activated or inactivated FBs were used for subrenal capsule transplantation. Mouse melanoma cell supernatants were used to activate FBs; the tests of the purity of the pancreatic islet cells of the donor, survival rate, and function of insulin secretion were performed to ensure high-quality transplants. Mice receiving the allogeneic transplantation were given tacrolimus and sirolimus to prevent rejection. The diabetic model was induced by streptozotocin.


RESULTS
Conditioned medium made of tumor cell supernatants was found to stimulate the expression of α-smooth muscle actin and vascular endothelial growth factor A to an extent notably greater than that of pancreatic islet transplantation alone or pancreatic islet transplantation combined with inactivated FBs. FBs from the recipient were associated with capillary density in the transplanted pancreatic islet most closely to that observed in isogenically transplanted pancreatic islets and the original pancreatic islet. In this way, activated FBs derived from the recipient combined with pancreatic transplantation were able to treat diabetes, and long-term survival was achieved.


CONCLUSIONS
The current research sheds new light on the revascularization of transplanted pancreatic islets: activated FBs derived from the recipients, when transplanted alongside pancreatic tissue, can promote revascularization inside the transplanted pancreatic islet.
Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chong Qing Medical University, Chong Qing, PR China.
Dingzhi
D
Liu
Heng
H
Xiao
Chengyou
C
Du
Shiqiao
S
Luo
Dewei
D
Li
Long
L
Pan
D000199:Actins / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D015153:Blotting, Western; D017077:Culture Media, Conditioned; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000628:therapy; D005347:Fibroblasts / Q000502:physiology*; D006085:Graft Survival; D007150:Immunohistochemistry; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000098:blood supply*; D016381:Islets of Langerhans Transplantation; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D018919:Neovascularization, Physiologic; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
D000199:Actins; D001786:Blood Glucose; D017077:Culture Media, Conditioned; D007328:Insulin; D042461:Vascular Endothelial Growth Factor A; C544013:alpha-smooth muscle actin, mouse; C467480:vascular endothelial growth factor A, mouse