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The Effect of Composite Pig Islet-Human Endothelial Cell Grafts on the Instant Blood-Mediated Inflammatory Reaction
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- Authors
- Issue Date
- 2009
- Publisher
- COGNIZANT COMMUNICATION CORP
- Citation
- CELL TRANSPLANTATION; Vol.18 1; 31-37
- Keywords
- Endothelial cells ; Humans ; Transplantation ; Swine ; Islets of Langerhans ; Heterologous
- Abstract
- 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 (<= 50% vs. >50%) or coculture time (<5 days vs. >= 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 <= 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.
- ISSN
- 0963-6897
- Language
- English
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