Mobilization of host stem cells enables long-term liver transplant acceptance in a strongly rejecting rat strain combination.
Mobilization of host stem cells enables long-term liver transplant acceptance in a strongly rejecting rat strain combination.
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DOI：
10.1111/j.1600-6143.2011.03698.x
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发表时间：
2011-10
期刊：
影响因子：
--
通讯作者：
Sun Z
中科院分区：
文献类型：
--
作者：
Okabayashi T;Cameron AM;Hisada M;Montgomery RA;Williams GM;Sun Z
仔细检查人类受体的肝、肾或心脏移植，发现移植物中有少量宿主骨髓来源的干细胞。如果目前观察到的供体移植物的有限受体再生可以促进，那么向主要宿主表型的转化可能会允许长期移植物功能而不会产生免疫抑制。我们提出“工程化”移植后的再繁殖，以一种强烈排斥肝移植的菌株组合（DA到Lewis GFP+），这种模型更接近于人类的情况。在移植后的第0、1、2、3和7天使用低剂量（0.1mg/kg）他克莫司(T)联合plerixafor (P)动员宿主干细胞，减少排斥反应，移植物存活超过180天，少量（50%）DA移植物广泛转化为受体Lewis GFP+基因型。随后的皮肤移植显示供体特异性移植物延长。T + P治疗导致第7天血液和肝脏中Lin-Thy1+CD34+CD133+干细胞和Foxp3+调节性T细胞水平升高。因此，宿主干细胞的药理动员通过两种机制维持同种异体肝移植：受损供体细胞的再生和免疫反应的调节。
Careful examination of liver, kidney or heart transplants in human recipients has revealed small numbers of host bone marrow derived stem cells in the graft. If the limited recipient repopulation of a donor graft that is currently observed could be facilitated, it is possible that conversion to a predominantly host phenotype would permit long term graft function without immunosuppression. We proposed to “engineer” repopulation after transplant in a strain combination (DA to Lewis GFP+) which rejects liver grafts strongly, a model which more closely resembles the situation in humans. Treatment on days 0,1,2,3 and 7 after transplantation with low-dose (0.1mg/kg) tacrolimus (T) designed to blunt rejection combined with plerixafor (P) to mobilize host stem cells resulted in greater than 180 day graft survival with extensive albeit spotty conversion of a small (50%) DA graft to the recipient Lewis GFP+ genotype. Subsequent skin grafting revealed donor specific graft prolongation. T plus P treatment resulted in higher levels of Lin-Thy1+CD34+CD133+ stem cells and Foxp3+ regulatory T cells in the blood and liver at day 7. Thus, pharmacological mobilization of host stem cells sustains liver allografts by two mechanisms: repopulation of injured donor cells, and regulation of the immune response.
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影响因子：
4.6
作者：
ten Hove, WR;van Hoek, B;Lagaaij, EL
通讯作者：
Lagaaij, EL
DOI：
10.1002/hep.22653
发表时间：
2009-02
期刊：
Hepatology (Baltimore, Md.)
影响因子：
--
作者：
Sun Z;Zhang X;Locke JE;Zheng Q;Tachibana S;Diehl AM;Williams GM
通讯作者：
Williams GM
DOI：
10.1084/jem.20090847
发表时间：
2009-12-21
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Francisco LM;Salinas VH;Brown KE;Vanguri VK;Freeman GJ;Kuchroo VK;Sharpe AH
通讯作者：
Sharpe AH
影响因子：
6.2
作者：
Idilman, R;Erden, E;Karayalcin, S
通讯作者：
Karayalcin, S
影响因子：
168.9
作者：
Gao, ZH;McAlister, VC;Williams, GM
通讯作者：
Williams, GM