| Project/Area Number |
13671253
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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 | SHOWA University |
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Principal Investigator |
KATO Hirohisa SHOWA University, Medicine, Assistant Professor, 医学部, 助手 (10286784)
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| Co-Investigator(Kenkyū-buntansha) |
KUSANO MITSUO SHOWA University, Medicine, Chief Professor, 医学部, 教授 (70091569)
MURAKAMI MASAHIKO SHOWA University, Medicine, Associate Professor, 医学部, 助教授 (70255727)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2002: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2001: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | ORGAN TRANSPLANTATION / GENE TRANSFER / TOLERANCE |
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| Research Abstract |
(Background) Gene transfer approach has the potential to introduce immunosuppressive molecules directly into the allograft, which in turn should limit systemic side effects of conventional immunosuppressive therapy to recipients. (Aim) To analyze the efficacy and putative mechanisms of adenoviral-mediated IL4 gene transfer in rat kidney transplant model. (Material ＆ Method) Renal allografts (BN rat) were perfused in-situ with Adex1CAmIL4 or AxCALacZ (RIKEN DNA Bank, respectively) incubated at 4C for 1.5, 24, 48, 72h (ex-vivo), or/and transplanted to LEW recipients. Adenovirus vector was perfused with 4C saline or UW solution, and renal grafts were preserved in 4C saline (1.5h) or UW solution (24-72h). (Results) 1. β-gal was detected after 24h preservation, but not 1.5h in ex-vivo model. After transplantation, there was mo staining of β-gal in renal allograft at day2/day7. 2. In ex-vivo preservation, IL4 was expressed in all of renal grafts (1.5h-72h) with Adex1CAmIL4 perfusion, even though it was not detected in control group perfused with cold saline in any preserved term. 3. Histological damage of renal allografts maintained for 24h after Adex1CAmIL4 gene transfer were diminished as compared with 1.5h preserved grafts at day7 after transplantation. (Conclusion) 24h preservation was prefer to induce immunosuppressive effects of Adenovirus-mediated IL4 gene therapy as compared. with 1.5h maintaining. It seems that appropriate expression of IL4 might be important at the early phase (day0-2) after transplantation. Further study will be necessary to inquire "optimal way" of gene transfer in transplant setting.
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