Composite islet-endothelial cell grafts: a novel approach to counteract innate immunity in islet transplantation.
An instant blood-mediated inflammatory reaction (IBMIR) is elicited when islets come in contact with blood after intraportal transplantation. In contrast, endothelial cells (EC) readily tolerate contact with blood. A conceivable strategy to overcome IBMIR would be to create composite islet-EC grafts. Human islets were co-cultured with primary human aortic endothelial cells (HAEC) for 2-7 days to obtain 50-90% coverage. HAEC-coated islets were exposed to ABO-identical blood and analyzed with regard to clotting time, signs of inflammation and cell infiltration. Composite islet-HAEC graft survival was assessed after transplantation to athymic (nu/nu) nude mice. Exposed to blood, HAEC-coated islets induced less activation of coagulation and complement compared to control islets. Also, platelet and leukocyte consumption in blood was decreased. Clots with entrapped HAEC-coated islets showed less infiltration of CD11b+ cells. The extent of protection correlated to the level of HAEC coverage. Transplanted composite grafts stained positive for insulin and PECAM-1 demonstrating presence of both islets and HAEC within the islet graft 7 weeks after transplantation. Composite islet-HAEC grafts reduce all components of IBMIR. Refinement of the technique will allow introduction of composite islet-EC grafts in clinical islet transplantation, using autologous EC expanded in vitro and kept frozen until allogeneic islets become available for that specific recipient.
Johansson
Ulrika
U
Department of Radiology, Oncology and Clinical Immunology, Division of Clinical Immunology, Uppsala University, Sweden. ulrika.johansson@klinimm.uu.se
Elgue
Graciela
G
Nilsson
Bo
B
Korsgren
Olle
O
D000818:Animals; D018929:Cell Culture Techniques / Q000379:methods; D042783:Endothelial Cells / Q000637:transplantation*; D006085:Graft Survival / Q000276:immunology; D006801:Humans; D007515:Islets of Langerhans / Q000166:cytology*; D016381:Islets of Langerhans Transplantation / Q000276:immunology*; D051379:Mice; D008819:Mice, Nude; D013370:Subrenal Capsule Assay; D014183:Transplantation, Heterologous / Q000502:physiology*