NOD-scid IL2rgamma(null) mouse model of human skin transplantation and allograft rejection.
NOD-scid IL2rgamma(null) mouse model of human skin transplantation and allograft rejection.
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DOI：
10.1097/tp.0b013e3181c90242
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发表时间：
2010-03-15
期刊：
影响因子：
6.2
通讯作者：
Greiner DL
中科院分区：
文献类型：
--
作者：
Racki WJ;Covassin L;Brehm M;Pino S;Ignotz R;Dunn R;Laning J;Graves SK;Rossini AA;Shultz LD;Greiner DL
将人皮肤移植到支持植入功能性人免疫系统的免疫缺陷小鼠上将是研究伤口愈合和移植机制的宝贵工具。NOD-scid IL 2 r γnull（NSG）易于与人类免疫系统移植，但人类皮肤移植完整性较差。相比之下，人皮肤移植物在CB 17-scid bg（SCID.bg）小鼠上的完整性是极好的，但它们与人免疫系统的移植较差。评价移植到免疫缺陷型NSG（SCID.bg）和其他免疫缺陷型菌株上的人皮肤移植物的移植物完整性、移植物内皮的保存及其在同种异体外周血单核细胞（PBMC）植入后被排斥的能力。移植到NSG小鼠上的人皮肤出现炎性浸润，主要由宿主Gr 1+细胞组成，这对移植物中人内皮细胞的存活是有害的。用抗Gr 1抗体治疗移植物受体可减少这种细胞浸润，保护移植物内皮，并促进伤口愈合、组织发育和移植物重塑。移植皮肤的良好移植完整性包括多层分层的人表皮、发育良好的人脉管系统、人成纤维细胞和过客白细胞。注射未分级的CD 4或CD 8同种异体人PBMC诱导移植皮肤移植物的快速破坏。用抗Gr 1抗体处理的NSG小鼠提供了一种针对人皮肤移植物完整性和功能性人免疫系统的植入进行优化的模型。该模型提供了研究协调炎症、伤口愈合、血运重建、组织重塑和同种异体移植排斥反应的机制的机会，并且可以为改善临床移植后的结果提供指导。
Transplantation of human skin on immunodeficient mice that support engraftment with functional human immune systems would be an invaluable tool for investigating mechanisms involved in wound healing and transplantation. NOD-scid IL2rγnull (NSG) readily engraft with human immune systems but human skin graft integrity is poor. In contrast, human skin graft integrity is excellent on CB17-scid bg (SCID.bg) mice, but they engraft poorly with human immune systems. Human skin grafts transplanted onto immunodeficient NSG, SCID.bg, and other immunodeficient strains were evaluated for graft integrity, preservation of graft endothelium and their ability to be rejected following engraftment of allogeneic peripheral blood mononuclear cells (PBMC). Human skin transplanted onto NSG mice develops an inflammatory infiltrate, consisting predominately of host Gr1+ cells, that is detrimental to the survival of human endothelium in the graft. Treatment of graft recipients with anti-Gr1 antibody reduces this cellular infiltrate, preserves graft endothelium, and promotes wound healing, tissue development and graft remodeling. Excellent graft integrity of the transplanted skin includes multilayered stratified human epidermis, well developed human vasculature, human fibroblasts and passenger leukocytes. Injection of unfractionated, CD4 or CD8 allogeneic human PBMC induces a rapid destruction of the transplanted skin graft. NSG mice treated with anti-Gr1 antibody provide a model optimized for both human skin graft integrity and engraftment of a functional human immune system. This model provides the opportunity to investigate mechanisms orchestrating inflammation, wound healing, revascularization, tissue remodeling, and allograft rejection and can provide guidance for improving outcomes following clinical transplantation.