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The intragraft vascularized bone marrow component plays a critical role in tolerance induction after reconstructive transplantation

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Cellular & Molecular Immunology 2021年第2期18卷 363-373页

作者： Cheng-Hung Lin Madonna R.Anggelia Hui-Yun Cheng Aline Yen Ling Wang Wen-Yu Chuang Chih-Hung Lin W.P.Andrew Lee Fu-Chan Wei Gerald Brandacher Center for Vascularized Composite Allotransplantation Department of Plastic and Reconstructive SurgeryChang Gung Memorial HospitalChang Gung Medical College and Chang Gung UniversityTaoyuanTaiwanChina Graduate Institute of Biomedical Sciences College of MedicineChang Gung UniversityTaoyuanTaiwanChina Department of Pathology Chang Gung Memorial HospitalChang Gung Medical College and Chang Gung UniversityTaoyuanTaiwanChina Department of Plastic and Reconstructive Surgery Chiayi Chang Gung Memorial HospitalChiayi CountyTaiwanChina Department of Plastic and Reconstructive Surgery Vascularized Composite Allotransplantation(VCA)LaboratoryJohns Hopkins University School of MedicineBaltimoreMDUnited States

The role of the vascularized bone marrow component as a continuous source of donor-derived hematopoietic stem cells that facilitate tolerance induction of vascularized composite allografts is not completely *** this study,vascularized composite tissue allograft transplantation outcomes between recipients receiving either conventional bone marrow transplantation(CBMT)or vascularized bone marrow(VBM)transplantation from Balb/c(H2d)to C57BL/6(H2b)mice were *** high-or low-dose CBMT(1.5×10^(8)or 3×10^(7)bone marrow cells,respectively)was *** addition,recipients were treated with costimulation blockade(1 mg anti-CD154 and 0.5 mg CTLA4Ig on postoperative days 0 and 2,respectively)and short-term rapamycin(3 mg/kg/day for the first posttransplant week and then every other day for another 3 weeks).Similar to high-dose conventional bone marrow transplantation,5/6 animals in the vascularized bone marrow group demonstrated long-term allograft survival(>120 days).In contrast,significantly shorter median survival was noted in the low-dose CBMT group(~64 days).Consistently high chimerism levels were observed in the VBM transplantation ***,low levels of circulating CD4^(+)and CD8^(+)T cells and a higher ratio of Treg to Teff cells were maintained in VBM transplantation and high-dose CBMT recipients(>30 days)but not in low-dose VBM transplant ***-specific hyporesponsiveness was shown in tolerant recipients in *** of the vascularized bone marrow component after secondary donor-specific skin transplantation did not affect either primary allograft or secondary skin graft survival.

关键词： Vascularized composite allotransplantation costimulation blockade Donor-specific tolerance Vascularized bone marrow transplantation Chimerism

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