2002 Fiscal Year Final Research Report Summary
cyclophosphamide plus Busulfan-induced tolerance in rat into mouse xenotransplantation
| Project/Area Number |
13671242
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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 | Kyushu University |
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Principal Investigator |
TOMITA Yukihiro Department of cardiovascular surgery Faculty of Medicine, Assistant Professor, 大学院・医学研究院, 講師 (90180174)
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| Co-Investigator(Kenkyū-buntansha) |
NISHIDA Takahiro Department of cardiovascular surgery FacultyofMedicine, Assistant Professor, 医学部付属病院, 助手 (50284500)
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| Project Period (FY) |
2001 – 2002
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| Keywords | cyclophosphamide / Busulfan / tolerance / anti-alpha Gal nAb / alpha-Gal knockout mouse / xenotransplantation / hyperacute rejection / B cell tolerance |
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| Research Abstract |
We have recently reported a new method of cyclophosphamide(CP) plus Busulfan (BU)-induced tolerance. Recently, we could established a modified method to induce both permanent mixed chimerism and skin allograft tolerance in H-2 mismatched combinations (J Immunol 2000; 164: 34). Our present protocol consists on injection of 1 x 10^8 allogeneic spleen cells (SC) on day 0, and administration of 200mg/kg CP and 30mg/kg BU on day 2 followed by 1 x 10^7 T cell-depleted donor bone marrow cells (BMC) on day 3. As a consequence, we also found that the correlation between the establishment of mixed chimerism and skin allograft tolerance and the clonal destruction as the major mechanisms of tolerance induction. In the present study, we applied our new system to rat into mouse xenograft tolerance. Mixed chimerism was detectable (5-20%) at 2-8 weeks after treatments, and F344 rat skins were significantly and specifically prolonged (median 40 days, max 75 days). However, neither permanent mixed chimerism nor skin xenograft tolerance could not be induced. NK cell-depletion did not permit more profound degree of mixed chimerism or induce more skin graft prolongation.. The present study indicated that our new protocol can induce temporal mixed chimerism and moderate skin graft polongation in a donor specific manner.
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