2001 Fiscal Year Final Research Report Summary
Induction of unresponsiveness by grafting cells given genotoxic stress
| 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)
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| Project Period (FY) |
2000 – 2001
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| Keywords | Mitomycin C / islet transplantation / allograft / xenograft / TGF-beta / genotoxic stress / glucose metabolism |
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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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Research Products
(12 results)
