| Project/Area Number |
12470244
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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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 | Fukushima Medical University |
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Principal Investigator |
GOTOH Mitsukazu Fukushima Med. Univ., Dept. of Surgl, Professor, 医学部, 教授 (50162160)
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| Co-Investigator(Kenkyū-buntansha) |
SAITO Takuro Fukushima Med. Univ., Dept. of Surgl, Instructor, 医学部, 助手 (20305361)
ABE Tsuyoshi Fukushima Med. Univ., Dept. of Surgl, Associate Professor, 医学部, 助教授 (90212547)
金沢 幸夫 福島県立医科大学, 医学部, 講師 (20177497)
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥13,700,000 (Direct Cost: ¥13,700,000)
Fiscal Year 2001: ¥6,400,000 (Direct Cost: ¥6,400,000)
Fiscal Year 2000: ¥7,300,000 (Direct Cost: ¥7,300,000)
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| Keywords | Mitomycin C / islet transplantation / allograft / xenograft / TGF-beta / genotoxic stress / glucose metabolism / transplantation / islet / TGF-β / immuno-histology |
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| Research Abstract |
We have shown that MMC pretreatment of islets induces upregulation of TGFβ within the graft, and protects islet graft from inflammatory cell infiltration in a rat-to-mouse xenogeneic combination. The present study was undertaken 1) to determine whether extension of culture period after MMC treatment could further prolong graft survival in a rat to mouse xenogeneic combination and 2) to determine a feasibility of MMC pretreatment of islet graft as a sole immunomodulatory regimen to protect murine islet allografts.
As for xenograft, WS rat islets treated with 10 μg /ml of MMC and cultured either for 20 hours or for 40 hours were transplanted into renal subcapsular space of streptozotocin-induced diabetic C57BL/6 mice. Median survival time of each group: culture for 20hrs (n=ll), MMC(+) + culture for 20hrs (n=12), culture for 40hrs (n=7) and MMC(+) + culture for 40hrs (n=7) was ll.9±2.5, 33.8±25.5, 20.3±4.8 and 50.1 ±10.9 days, respectively. Marked prolongation was obtained with MMC treatment and 40hr culture as compared to other protocols.
As for allograft survival, all untreated BALB/c (H-2d) islets were acutely rejected with a MST of 14.7±3.5 days in streptozotocin-induced diabetic C57BL/6 (B6 ; H-2b) mice. Significant prolongation of graft survival was obtained in the groups of animals given MMC-treated islets at concentrations of 10 or 32μg/ml compared with untreated group (59.1±37.7, 21.5±10.8 vs 14.7±3.5 days, P<0.01). Furthermore, antigen specific prolongation of graft survival of secondary untrated islets was observed in animals bearing long-term functioning islet graft.
These results indicate that MMC treatment and long-term culture could produce significant prolongation of xenograft survival over the either treatment alone, and that MMC pretreatment of islet allograft alone could protect the graft from rejection response, offering a new strategy for islet xeno- and allotransplantation.
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