The effect of composite pig islet-human endothelial cell grafts on the instant blood-mediated inflammatory reaction.
Instant blood-mediated inflammatory reaction (IBMIR) causes rapid islet loss in portal vein islet transplantation. Endothelial cells are known to protect against complement-mediated lysis and activation of coagulation. We tested composite pig islet-human endothelial cell grafts as a strategy to overcome IBMIR. Porcine islets were cocultured with human endothelial cells in specially modified culture medium composed of M199 and M200 for 1-9 days. A positive control group, negative control group, and the endothelial cell-coated group were examined with an in vitro tubing loop assay using human blood. The endothelial cell-coated group was subdivided and analyzed by degree of surface coverage by endothelial cells (< or = 50% vs. > 50%) or coculture time (< 5 days vs. > or = 5 days). Platelet consumption and complement and coagulation activation were assessed by platelet count, C3a, and thrombin-antithrombin complex (TAT), respectively. After 60-min incubation in human blood, the endothelial cell-coated group showed platelet consumption inhibition and low C3a and TAT assay results compared to uncoated controls. When the endothelial cell-coated group was subdivided by degree of surface coverage, the < or = 50% coated group showed less platelet consumption and less activation of complement and coagulation compared with the positive control (uncoated) group. On analysis by coculture time, only the subgroup cocultured for < 5 days showed the same protective effect. Human endothelial cell-coated pig islets, especially the partially coated and short-term cocultured pig islet-human endothelial cell composites, reduced all components of IBMIR. If the optimal endothelial cell-islet coculture method could be identified, human endothelial cell coating of pig islets would offer new strategies to improve xenogenic islet transplantation outcomes.
Kim
Hyoung-Il
HI
Xenotransplantation Research Center, Seoul 110-744, Republic of Korea.
Yu
Jae Eun
JE
Lee
Song Yi
SY
Sul
A Young
AY
Jang
Min Seok
MS
Rashid
M A
MA
Park
Sang Gyu
SG
Kim
Sang Jun
SJ
Park
Chung-Gyu
CG
Kim
Jae Hyeon
JH
Park
Kyong Soo
KS
D000818:Animals; D042783:Endothelial Cells / Q000276:immunology / Q000637:transplantation*; D006085:Graft Survival / Q000276:immunology; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000276:immunology*; D007515:Islets of Langerhans / Q000166:cytology* / Q000276:immunology; D016381:Islets of Langerhans Transplantation / Q000276:immunology*; D013552:Swine; D014183:Transplantation, Heterologous / Q000276:immunology*