2002 Fiscal Year Final Research Report Summary
Research for immuno-logical tolerance induction in islet xeno-transplantation -Therapeutic effect of a adenovirus or retrovirus mediated CTLA4Ig gene transfer combined with immunosuppressive regents-
| Project/Area Number |
13671233
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General surgery
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| Research Institution | Osaka University |
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Principal Investigator |
NAKATA Seizou Osaka University Hospital, Associate Professor, 医学部附属病院, 助教授 (50116068)
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| Co-Investigator(Kenkyū-buntansha) |
SHIMIZU Shigeomi Osaka University Graduate School of Medicine, Associate Professor, 医学系研究科, 助教授 (70271020)
ITO Toshinori Osaka University Graduate School of Medicine, Associate Professor, 医学系研究科, 助教授 (20231152)
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| Project Period (FY) |
2001 – 2002
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| Keywords | Islet / adenoviral vector / CTLA4Ig / FK506 |
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| Research Abstract |
【 Background & Aims 】 Adenovirus-mediated CTLA4Ig gene transfer has been reported to enhance graft survival in several rodent vansplantation models. In this study, we investigated the efficacy of ex vivo and systemic transfer of the CTLA4Ig gene by adenoviral vectors in pancreatic islet allo-transplantation.
【Methods】 Islet grafts from BN rats were transplanted to chemically induced diabetic LEW rats. First, ex vivo CTLA4Ig gene transfer into isolated islets was performed prior to transplantation. Secondly, systemic gene transfer was accomplished by intravenous administration immediately after the transplantation procedure.
【 Results 】 Survival of transduced grafts under the kidney capsule was slightly prolonged (8.6±1.3 days) compared with survival of untransduced grafts (6.7±1.2 days); when combined with a short course of FK506, graft survival was further extended (32.6±10.7 days vs. 13.7±1.0 days with FK506 alone).
In systemically transduced animals, islet grafts under the kidney capsule survived longer (15.2±3.3 days) than in controls (6.7±1.2 days) , and when FK506 was administered perioperatively, all the islet grafts survived for more than 100 days. Finally, the LEW recipients with long-surviving islet were re-transplanted with islet grafts from the same donor strain (BN) on day 100. However, the second islet grafts consistently failed in the recipients.
【Conclusions】 We conclude that in this transplant model, CTLA4Ig gene transfer and FK506 treatment synergistically improved islet graft survival, systemic transfer of the gene was more effective than ex vivo transfer to the islets, and donor-specific tolerance could not be achieved for islet transplantation.
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