Host stem cells repopulate liver allografts: reverse chimerism.
Host stem cells repopulate liver allografts: reverse chimerism.
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DOI：
10.4161/chim.2.4.19177
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发表时间：
2011-10-01
期刊：
影响因子：
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通讯作者：
Williams, George Melville
中科院分区：
文献类型：
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作者：
Sun, Zhaoli;Williams, George Melville
在美国，肝移植已经成为成千上万患有终末期肝病的患者的挽救生命的疗法，但是慢性排斥反应和免疫抑制的毒性仍然是进一步扩展这种模式的重大障碍，并且“移植耐受性”仍然是该领域的中心目标。因此，我们和其他人正在寻找替代的移植后策略。我们开始在一种强烈排斥肝移植物的菌株组合[暗琼脂糖（DA）与刘易斯绿色荧光蛋白+（LEW GFP+）]中“工程化”移植后的再增殖，这是一种更接近人类情况的模型。我们的中心发现是有目的地操纵免疫反应，低剂量的免疫抑制和干细胞的释放移植后很短的时间内，结果在长期的移植接受两种机制：转化肝脏（供体）的自我（宿主）表型，和特定的同种异体移植反应的自抑制。
Liver transplant has become life-saving therapy for thousands of patients with end stage liver disease in the United States, but chronic rejection and the toxicities of immunosuppression remain significant obstacles to the further expansion of this modality and "transplant tolerance" remains a central goal in the field. So we and others are looking for alternative post-transplant strategies. We set out to 'engineer' repopulation after transplantation in a strain combination [dark agouti (DA) to Lewis green fluorescent protein+ (LEW GFP+)] which rejects liver grafts strongly, a model that more closely resembles the situation in humans. Our central finding is purposeful manipulation of the immune response with low dose immunosuppression and liberation of stem cells for a very short period after transplantation results in long-term transplant acceptance by two mechanisms: transforming the liver (donor) to self (host) phenotype, and auto-suppression of the specific allograft response.