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Controlling coagulation dysregulation in xenotransplantation) t+ R i4 r8 ?* _2 Q
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1.说明：原文来源自http://journals.lww.com/co-trans ... ation_in.99778.aspx
* Q/ i( L5 C( L0 Y6 R i9 h! H6 Y* ^9 N由干细胞之家新闻小组成员Hyde翻译（转帖请注明）
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2.翻译内容
# c' c; W8 x% M% s. t8 V摘要：
$ d+ ]$ z; U6 K- y% B/ u综述目的：猪是异种移植的可选供体之一。研究者通过敲除其α1,3半乳糖基转移酶基因，消除了异种移植免疫排斥反应中一种主要的异种抗原。但是这一工作并没有阻止异种移植后血管损伤和凝血功能失常的发生。在GalT敲除的异种移植物引起的排斥反应中总是能看到血栓形成和（血小板隔离）platelet sequestration？的迹象，在灵长类受者中出现消耗性凝血病（ consumptive coagulopathy？）的频率比较高。本篇综述归纳总结最近关于该问题发生机制的相关研究。# `% E' ^7 @( G2 i4 h- V
' B( o+ c* ], c最近的发现：异种移植引起的凝血存在着器官的差异性，可能是由于不同器官的脉管系统的差异性引起的。异种移植的肾脏比心脏更容易出现消耗性凝血病，这可能是因为differential transcriptional responses？。肝脏移植会导致受者的血小板在短时间内急剧减少，导致受者凝血功能异常，因为大量出血而在几天内死亡。体外实验的数据表明，是肝内皮细胞和肝细胞通过coagulation-independent process?导致了血小板的耗竭。8 C. U2 c8 w! h# i
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有人提出，在血小板和单核细胞存在组织因子受体是导致消耗性凝血病的一个主要起因。最后（？），表达人类抗凝剂和抗凝物的转基因猪被推出了生产线，但是还没有经过严格的检测。! M8 T9 A1 i/ y
0 o* U# b q( T: _总结：克服异种移植中的凝血异常，可能需要针对不同的器官，联合考虑药理学和遗传学策略进行处理。
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4 e! \5 Y) a7 ~+ `5 m8 A3.原文. I) j3 E( n+ h- X% s# Y
Abstract
! T9 V& \& T( T N4 v" mPurpose of review: Deletion of the [alpha]1,3-galactosyltransferase (GalT) gene in pigs has removed a major xenoantigen but has not eliminated the problem of dysregulated coagulation and vascular injury. Rejecting GalT knockout organ xenografts almost invariably show evidence of thrombosis and platelet sequestration, and primate recipients frequently develop consumptive coagulopathy. This review examines recent findings that illuminate potential mechanisms of this current barrier to successful xenotransplantation.
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Recent findings: The coagulation response to xenotransplantation differs depending on the type of organ and quite likely the distinct vasculatures. Renal xenografts appear more likely to initiate consumptive coagulopathy than cardiac xenografts, possibly reflecting differential transcriptional responses. Liver xenografts induce rapid and profound thrombocytopenia resulting in recipient death within days due to bleeding; ex-vivo data suggest that liver endothelial cells and hepatocytes are responsible for platelet consumption by a coagulation-independent process.
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It has been proposed that expression of recipient tissue factor on platelets and monocytes is an important trigger of consumptive coagulopathy. Finally, pigs transgenic for human anticoagulants and antithrombotics are slowly but surely coming on line, but have not yet been rigorously tested to date.
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. L7 y; \7 R$ V6 D+ g7 B8 L5 _Summary: Successful control of coagulation dysregulation in xenotransplantation may require different combinatorial pharmacological and genetic strategies for different organs.) j4 p& k" u' M+ H7 ]! l/ l
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(C) 2011 Lippincott Williams & Wilkins, Inc.- t. S3 ]( n: F& [
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4.注明：个人翻译，理解不准确的语句还望大家积极指出。$ U3 j5 x3 @- K% R; P
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最近在看猪到人异种移植的paper，好烦……看的云里雾里的……晕……8 A3 C2 Y h2 L" [' L0 [% z
求高人推荐Paper关于--猪到人（或猿猴等类似的灵长类动物）-异种移植发生的免疫排斥反应的发生机制和相关基因--（这个题目是不是太大？） |
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发表于 2011-2-10 21:48
小鼠异体移植好像排异不是很强烈的吧。 这里有一篇小鼠骨髓移植的文献。Characterization of Transplanted Green Fluorescent Protein Bone。 灵长类和纯种猪的貌似都米有找到文献。
