Markedly decreased blood perfusion of pancreatic islets transplanted intraportally into the liver: disruption of islet integrity necessary for islet revascularization.
Experimental studies indicate low revascularization of intraportally transplanted islets. This study aimed to quantify, for the first time, the blood perfusion of intrahepatically transplanted islets and elucidate necessary factors for proper islet graft revascularization at this site. Yellow chameleon protein 3.0 islets expressing fluorescent protein in all cells were transplanted. Graft blood perfusion was determined by microspheres. The vascular density and relative contribution of donor blood vessels in revascularization was evaluated using islets expressing green fluorescent protein under the Tie-2 promoter. Blood perfusion of intrahepatic islets was as a mean only 5% of that of native islets at 1-month posttransplantation. However, there was a marked heterogeneity where blood perfusion was less decreased in islets transplanted without prior culture and in many cases restored in islets with disrupted integrity. Analysis of vascular density showed that distorted islets were well revascularized, whereas islets still intact at 1-month posttransplantation were almost avascular. Few donor endothelial cells were observed in the new islet vasculature. The very low blood perfusion of intraportally transplanted islets is likely to predispose for ischemia and hamper islet function. Since donor endothelial cells do not expand posttransplantation, disruption of islet integrity is necessary for revascularization to occur by recipient blood vessels.
Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden.
Johanna
J
Henriksnäs
Joey
J
Lau
Guangxiang
G
Zang
Per-Olof
PO
Berggren
Martin
M
Köhler
Per-Ola
PO
Carlsson
D000818:Animals; D020869:Gene Expression Profiling; D007515:Islets of Langerhans / Q000098:blood supply*; D016381:Islets of Langerhans Transplantation; D008099:Liver / Q000601:surgery*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018919:Neovascularization, Physiologic; D012039:Regional Blood Flow; D042461:Vascular Endothelial Growth Factor A / Q000502:physiology
D042461:Vascular Endothelial Growth Factor A