Project/Area Number |
08457384
|
Research Category |
Grant-in-Aid for Scientific Research (B)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Orthopaedic surgery
|
Research Institution | Niigata University |
Principal Investigator |
SHIBATA Minoru Niigata University Medical Hospital Professor, 医学部・附属病院, 教授 (50196432)
|
Co-Investigator(Kenkyū-buntansha) |
WATANABE Hisami Niigata University School of Medicine assistant, 医学部, 助手 (50143756)
|
Project Period (FY) |
1996 – 1997
|
Project Status |
Completed (Fiscal Year 1997)
|
Budget Amount *help |
¥8,400,000 (Direct Cost: ¥8,400,000)
Fiscal Year 1997: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1996: ¥7,500,000 (Direct Cost: ¥7,500,000)
|
Keywords | anti-CD2 antibody / Allograft / Skin graft / monochlonal antibody / 超低温保存 / モノクローナル抗体 / CD2 / manalonal antibody / cryopeservation / Allograft |
Research Abstract |
Introduction : It is well accepted to use immuno-suppressing agents for the allografting of the important organs such as heart, lung, liver or kidney. However, these agents do have side effects and it is difficult to justify to use these drugs for the transfer of other non-vital organs or tissues. Development of tissue transfer without using these agents would extend indications for non-vital organs or tissues for the reconstruction of complicated defect after sever trauma or malignant tumor resection. We used anti-CD2 monoclonal antibodies (mAbs) for allo-skin grafting in rat major mismatch model. Materials and Metods : Major mismatch model of Lewis (LEW) and Brown Norway (BN) rats was used. Rat anti-CD2 monoclonal antibiesantibodies was made by intra-peritoneal injection of cultured hybridoma cell (OX34) to mouse. The effective dose of created antibodies was determined as 2 mg/kg by flow-cytometry. Two successful heterotopic heart transplantation from BN to LEW rat were demonstrated b
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y the twice administration of the same dose antibodies before and after surgery. Full thickness abdominal skin (2 sheets of 1.5x2 cm skin) of BN rats was grafted onto the back of LEW.Three groups were created. Group A (12 grafts) : control Group B (12 grafts) : Anti-CD2 mAbs of 2 mg/kg were injected intraperitoneally to LEW rats for 2 consecutive days beginning two days before grafting. Group C (12 grafts) : same dose injection for 9 consecutive days beginning one day before grafting. Mixed lymphocyte reaction test using PVG as the third party was performed to evaluate lymphocyte function of the recipient rat. Results : Skin grafts of untreated rats or those of 2 day treated rats were all rejected within 10 days postoperatively. In contrast, grafted skin of rats treated for 9 days survived for than 20 days (mean survival period : 51 days, longest : 98 days). Mixed lymphocyte reaction test showed that group A demonstrated more reaction to BN than PVG and group B showed similar strong reaction to both BN and PVG suggesting recovery of lymphocyte function 2 weeks after mAbs administration. In group C,reaction to BN and PVG was less than that in group A or B and significantly stronger reaction to PVG suggesting more generalized suppression to lymphocyte function 2 weeks after 9 consecutive administration of mAbs. Discussion : This report shows that anti-CD2 monoclonal antibody treatment may significantly delay rejection of allo-skin grafting in major mismatched rat model. Considering the difficulty in allo-skin grafting, other allo-tissue transfer using anti-CD2 monoclonal antibodies for total limb, joint or nerve may be more successful. Less
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