Surface modification of pancreatic islets using heparin-DOPA conjugate and anti-CD154 mAb for the prolonged survival of intrahepatic transplanted islets in a xenograft model

Title
Surface modification of pancreatic islets using heparin-DOPA conjugate and anti-CD154 mAb for the prolonged survival of intrahepatic transplanted islets in a xenograft model
Author(s)
정지헌정윤석[정윤석]육심명[육심명]임복현[임복현]서진원[서진원]홍성우[홍성우]박준범[박준범]Victor C. Yang[Victor C. Yang]이동윤[이동윤]변영로[변영로]
Keywords
MEDIATED INFLAMMATORY REACTION; MONOCLONAL-ANTIBODY; EDMONTON PROTOCOL; TISSUE FACTOR; BLOOD; XENOTRANSPLANTATION; LANGERHANS; PEGYLATION; ALLOGRAFT; ADHESIVE
Issue Date
201201
Publisher
ELSEVIER SCI LTD
Citation
BIOMATERIALS, v.33, no.1, pp.295 - 303
Abstract
This study proposes a combination method of using 3,4-dihydorxy-t-phenylalanine (DOPA) conjugated heparin (heparin-DOPA) and a low dose of anti-CD154 monoclonal antibody (MR-1) treatment to improve the survival time of intrahepatic islet xenograft. To inhibit instant blood mediated inflammatory reactions, heparin-DOPA was directly grafted to the pancreatic islet surface. The surface coverage of heparin-DOPA, the viability and functionality of heparin-DOPA grafted islets were evaluated. In addition, the combined effect of grafted heparin-DOPA and a low dose of MR-1 (a T-cell targeting immunosuppressive drug) on the survival of islet was evaluated in a xenograft model. Both unmodified islets and heparin-DOPA grafted islets were completely rejected within 2 weeks after intraportal transplantation. However, when 0.1 mg/mouse of MR-1 was administered (at day 0, 2, 4, 6 of transplantation) to 11 mice that had heparin-DOPA grafted islets transplanted to, seven out of the recipients maintained normo-glycemia over 60 days. Therefore, we propose that a developed combinatory immunoprotection protocol of surface modification of pancreatic islets using heparin-DOPA with a low dose of MR-1 can be effective in prolonging the survival rate of transplanted islets in a xenograft model. (C) 2011 Elsevier Ltd. All rights reserved.
URI
http://hdl.handle.net/YU.REPOSITORY/30038http://dx.doi.org/10.1016/j.biomaterials.2011.09.051
ISSN
0142-9612
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약학대학 > 약학부 > Articles
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