Dual islet transplantation modeling of the instant blood-mediated inflammatory reaction.
Dual islet transplantation modeling of the instant blood-mediated inflammatory reaction.
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DOI：
10.1111/ajt.13098
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发表时间：
2015-05
期刊：
影响因子：
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通讯作者：
Kirk AD
中科院分区：
文献类型：
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作者：
Martin BM;Samy KP;Lowe MC;Thompson PW;Cano J;Farris AB;Song M;Dove CR;Leopardi FV;Strobert EA;Jenkins JB;Collins BH;Larsen CP;Kirk AD
异种胰岛移植是一种潜在的治疗糖尿病的方法，没有组织可用性的限制。虽然实验上是成功的，但早期胰岛损失仍然很大，并归因于即时血液介导的炎症反应（IBMIR）。这种胰岛破坏综合征的定义不完全，猪到灵长类动物模型的特征描述受到大型动物研究的后勤和统计限制的阻碍。为了进一步研究IBMIR，我们开发了一种新的体内双胰岛移植模型，以精确表征IBMIR作为概念验证，该模型可以用于适当控制比较修饰的异种胰岛制剂的实验。在非免疫抑制恒河猴中研究了野生型（WT）和α 1，3-半乳糖基转移酶敲除（GTKO）新生猪胰岛（NPI）。惰性聚乙烯微球作为门静脉栓塞效应的对照。在门静脉内胰岛输注后1小时和24小时，对靶向IBMIR介质的免疫组织化学进行数字分析。在移植的胰岛中观察到的早期发现包括补体和抗体沉积，以及中性粒细胞、巨噬细胞和血小板的浸润。胰岛素、补体、抗体、中性粒细胞、巨噬细胞和血小板在GTKO和WT胰岛之间相似，在两种表型中在24小时时巨噬细胞浸润增加。该模型提供了一个客观的和内部控制的研究不同的胰岛制剂和文件的时间组织学IBMIR。
Islet xenotransplantation is a potential treatment for diabetes without the limitations of tissue availability. Although successful experimentally, early islet loss remains substantial and attributed to an instant blood mediated inflammatory reaction (IBMIR). This syndrome of islet destruction has been incompletely defined and characterization in pig-to-primate models has been hampered by logistical and statistical limitations of large animal studies. To further investigate IBMIR, we developed a novel in vivo dual islet transplant model to precisely characterize IBMIR as proof-of-concept that this model can serve to properly control experiments comparing modified xenoislet preparations. Wild-type (WT) and α1,3-galactosyltransferase knockout (GTKO) neonatal porcine islets (NPIs) were studied in non-immunosuppressed rhesus macaques. Inert polyethylene microspheres served as a control for the effects of portal embolization. Digital analysis of immunohistochemistry targeting IBMIR mediators was performed at one and 24 hours after intraportal islet infusion. Early findings observed in transplanted islets include complement and antibody deposition, and infiltration by neutrophils, macrophages, and platelets. Insulin, complement, antibody, neutrophils, macrophages, and platelets were similar between GTKO and WT islets, with increasing macrophage infiltration at 24 hours in both phenotypes. This model provides an objective and internally controlled study of distinct islet preparations and documents the temporal histology of IBMIR.