A Small Animal Model of Ex Vivo Normothermic Liver Perfusion
A Small Animal Model of Ex Vivo Normothermic Liver Perfusion
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DOI：
10.3791/57541
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发表时间：
2018-06-01
影响因子：
1.2
通讯作者：
Black, Sylvester M.
中科院分区：
文献类型：
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作者：
Beal, Eliza W.;Dumond, Curtis;Black, Sylvester M.
可用于移植的肝脏同种异体移植物严重短缺，作为回应，供体标准已经扩大。因此，常温离体肝脏灌注（NEVLP）已被引入作为一种方法来评估和修改器官功能。与低温和亚常温灌注相比，NEVLP具有许多优点，包括减少保存损伤，在生理条件下恢复正常器官功能，评估器官性能，以及作为器官修复，重塑和修饰的平台。已经描述了鼠和猪NEVLP模型。我们展示了NEVLP的大鼠模型，并使用该模型来展示其重要应用之一-使用添加到肝脏灌注液中的治疗分子。过氧化氢酶是一种内源性活性氧（ROS）清除剂，已被证明可以减少眼、脑和肺的缺血-再灌注。聚乙二醇化已显示将过氧化氢酶靶向内皮。在这里，我们添加聚乙二醇化过氧化氢酶（PEG-CAT）的基础灌注液，并证明其能够减轻肝脏保存损伤。我们的啮齿类动物NEVLP模型的一个优点是，它是比较便宜的大型动物模型。本研究的局限性在于目前不包括灌注后肝移植。因此，不能确定地预测器官移植后的功能。然而，大鼠肝移植模型已经建立，当然可以与该模型结合使用。总之，我们已经证明了一种廉价，简单，易于复制的NEVLP模型使用大鼠。该模型的应用可以包括测试新的灌注液和灌注液添加剂、设计用于器官评估的测试软件以及设计用于修复器官的实验。
There is a significant shortage of liver allografts available for transplantation, and in response the donor criteria have been expanded. As a result, normothermic ex vivo liver perfusion (NEVLP) has been introduced as a method to evaluate and modify organ function. NEVLP has many advantages in comparison to hypothermic and subnormothermic perfusion including reduced preservation injury, restoration of normal organ function under physiologic conditions, assessment of organ performance, and as a platform for organ repair, remodeling, and modification. Both murine and porcine NEVLP models have been described. We demonstrate a rat model of NEVLP and use this model to show one of its important applications - the use of a therapeutic molecule added to liver perfusate. Catalase is an endogenous reactive oxygen species (ROS) scavenger and has been demonstrated to decrease ischemia-reperfusion in the eye, brain, and lung. Pegylation has been shown to target catalase to the endothelium. Here, we added pegylated-catalase (PEG-CAT) to the base perfusate and demonstrated its ability to mitigate liver preservation injury. An advantage of our rodent NEVLP model is that it is inexpensive in comparison to larger animal models. A limitation of this study is that it does not currently include post-perfusion liver transplantation. Therefore, prediction of the function of the organ post-transplantation cannot be made with certainty. However, the rat liver transplant model is well established and certainly could be used in conjunction with this model. In conclusion, we have demonstrated an inexpensive, simple, easily replicable NEVLP model using rats. Applications of this model can include testing novel perfusates and perfusate additives, testing software designed for organ evaluation, and experiments designed to repair organs.