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
- Authors
- Jung, Yoon Suk; Jeong, Jee-Heon; Yook, Simmyung; Im, Bok-Hyeon; Seo, Jinwon; Hong, Sung Woo; Park, Jun-Beom; Yan, Victor C.; Lee, Dong Yun; Byun, Youngro
- Issue Date
- Jan-2012
- Publisher
- ELSEVIER SCI LTD
- Keywords
- Islet transplantation; Surface modification; Heparin; DOPA; Anti-CD154 monoclonal antibody
- Citation
- BIOMATERIALS, v.33, no.1, pp.295 - 303
- Indexed
- SCIE
SCOPUS
- Journal Title
- BIOMATERIALS
- Volume
- 33
- Number
- 1
- Start Page
- 295
- End Page
- 303
- URI
- https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/166502
- DOI
- 10.1016/j.biomaterials.2011.09.051
- ISSN
- 0142-9612
- 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.
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