Vascularized composite allograft tolerance across MHC barriers in a large animal model.
Vascularized composite allograft tolerance across MHC barriers in a large animal model.
复制标题
DOI：
10.1111/ajt.12560
复制
发表时间：
2014-02
期刊：
影响因子：
--
通讯作者：
Cetrulo CL Jr
中科院分区：
文献类型：
--
作者：
Leonard DA;Kurtz JM;Mallard C;Albritton A;Duran-Struuck R;Farkash EA;Crepeau R;Matar A;Horner BM;Randolph MA;Sachs DH;Huang CA;Cetrulo CL Jr
血管化复合同种异体移植物（VCA）移植可以恢复严重颅面损伤、四肢截肢或大量组织丢失后的形态和功能。移植耐受的诱导将消除长期免疫抑制的需要，重新调整这些改善生命的手术的风险-收益比。皮肤是VCA的重要组成部分，一直以来对移植耐受性提出了最严格的挑战。在这里，我们在一个临床相关的微型猪模型中证明，通过诱导稳定的造血混合嵌合，诱导VCAs跨越MHC屏障的免疫耐受。受体条件调节包括造血细胞移植（HCT）前用cd3免疫毒素消耗T细胞，100 cGy全身照射和45天环孢素a疗程。VCA移植可同时进行诱导混合嵌合或在85-150天后建立混合嵌合体。在停止免疫抑制后，移植到稳定嵌合体中的vca （n =4）和在HCT时移植的vca （n =2）接受了包括皮肤在内的所有成分，在移植后115-504天的实验终点没有出现排斥反应的证据。这些数据表明，在临床相关的VCA模型中，可以诱导MHC错配的耐受性，为长期无免疫抑制生存的概念提供了证据。
Vascularized composite allograft (VCA) transplantation can restore form and function following severe craniofacial injuries, extremity amputations or massive tissue loss. The induction of transplant tolerance would eliminate the need for long-term immunosuppression, realigning the risk–benefit ratio for these life-enhancing procedures. Skin, a critical component of VCA, has consistently presented the most stringent challenge to transplant tolerance. Here, we demonstrate, in a clinically relevant miniature swine model, induction of immunologic tolerance of VCAs across MHC barriers by induction of stable hematopoietic mixed chimerism. Recipient conditioning consisted of T cell depletion with CD3-immunotoxin, and 100 cGy total body irradiation prior to hematopoietic cell transplantation (HCT) and a 45-day course of cyclosporine A. VCA transplantation was performed either simultaneously to induction of mixed chimerism or into established mixed chimeras 85–150 days later. Following withdrawal of immunosuppression both VCAs transplanted into stable chimeras (n =4), and those transplanted at the time of HCT (n =2) accepted all components, including skin, without evidence of rejection to the experimental end point 115–504 days posttransplant. These data demonstrate that tolerance across MHC mismatches can be induced in a clinically relevant VCA model, providing proof of concept for long-term immunosuppression-free survival.
登录
查看更多内容
影响因子：
17.1
作者：
Leventhal J;Abecassis M;Miller J;Gallon L;Ravindra K;Tollerud DJ;King B;Elliott MJ;Herzig G;Herzig R;Ildstad ST
通讯作者：
Ildstad ST
影响因子：
6.2
作者：
Kuo, Yur-Ren;Goto, Shigeru;Lee, W. P. Andrew
通讯作者：
Lee, W. P. Andrew
影响因子：
64.8
作者：
Jiang, Xiaodong;Clark, Rachael A.;Liu, Luzheng;Wagers, Amy J.;Fuhlbrigge, Robert C.;Kupper, Thomas S.
通讯作者：
Kupper, Thomas S.
影响因子：
17.1
作者：
Clark RA;Watanabe R;Teague JE;Schlapbach C;Tawa MC;Adams N;Dorosario AA;Chaney KS;Cutler CS;Leboeuf NR;Carter JB;Fisher DC;Kupper TS
通讯作者：
Kupper TS
影响因子：
6.2
作者：
Mathes DW;Hwang B;Graves SS;Edwards J;Chang J;Storer BE;Butts-Miwongtum T;Sale GE;Nash RA;Storb R
通讯作者：
Storb R