| Project/Area Number |
11671161
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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 Midicine, Associate Professor, 医学系研究科, 助教授 (20231152)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,900,000)
Fiscal Year 2000: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1999: ¥2,600,000 (Direct Cost: ¥2,600,000)
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| Keywords | islet / CTLA4-Ig / Fas Ligand / Bcl-2 / BB-rat / IDDM / NKT cells / NKT細胞 / Fas Ligand / インスリン依存型糖尿病 / 膵島移植 |
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| Research Abstract |
Insulin-dependent diabetes mellitus (IDDM) is an autoimmune disease caused by the βcells destruction by autoreactive T cells. Islet transplantation is expected as an ideal therapy of the disease, but the outcome of isolated islet transplantation has been disappointing. Recently the gene therapy is applied to the transplantation models. Especially Bcl-2 which controls apoptosis, Fas Ligand which leads T cells to apoptosis, and CTLA4-Ig which inhibits T cell activation, are expected to restrain the rejection. In the present study, we investigated the effect of the transfection of these molecules to islets.
It was revealed that the transfection of these molecules to islets by HVJ-liposome method is impossible. On the other hand , the transfection using adenovisrus vectors to islets worked efficiently.
Islet survival transfected CTLA4-Ig gene did not prolonged despite the expression of the protein. Systemic administration of Ad.CTLA4-Ig could prolong the islet graft survival (10.0±2.4 days v.s. 5.7±0.5 days of no treatment group survival). Furthermore, the adenovirus-mediated CTLA4-Ig gene transfer combined with FK506 significantly prolonged islet graft survival more than 100 days.
We have demonstrated that IDDM graft recurrence in the pancreas graft could be prevented with the administration of anti- ICAM-1/LEA-1 mAbs in a Wistar-Furth to a spontaneously diabetes prone-BB rat whole pancreatico- duodenal transplantation model. In this model, donor-derived chimeric RT6+ NKT cells which originated from the lymphoid tissues in the donor graft might be related to the inhibition of IDDM recurrence
Shimizu et al. advanced the basic research of Bcl-2 families and demonstrated that the Bcl-2 family of proteins bind to the VDAC in order to regulate the mitochondrial membrane potential and the release of cytochrome c during apoptosis.
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