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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
Kim, Hyoung-Il; Yu, Jae Eun; Lee, Song Yi; Sul, A. Young; Rashid, M. A.; Kim, Sang Jun; Kim, Jae Hyeon; Park, Kyong Soo; Park, Chung-Gyu; Park, Sang Gyu; Jang, Min Seok
Issue Date
2009
Publisher
COGNIZANT COMMUNICATION CORP
Citation
CELL TRANSPLANTATION; Vol.18 1; 31-37
Keywords
Endothelial cellsHumansTransplantationSwineIslets of LangerhansHeterologous
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
URI
http://hdl.handle.net/10371/77354
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College of Medicine/School of Medicine (의과대학/대학원)Internal Medicine (내과학전공)Journal Papers (저널논문_내과학전공)
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