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大鼠模型揭示的肝移植结局的免疫学决定因素。

Immunological Determinants of Liver Transplant Outcomes Uncovered by the Rat Model.

机构信息

Department of Immunology, University of Toronto, Toronto, ON, Canada.

Ajmera Family Transplant Centre, Toronto General Hospital Research Institute, Toronto, ON, Canada.

出版信息

Transplantation. 2021 Sep 1;105(9):1944-1956. doi: 10.1097/TP.0000000000003598.

Abstract

For many individuals with end-stage liver disease, the only treatment option is liver transplantation. However, liver transplant rejection is observed in 24%-80% of transplant patients and lifelong drug regimens that follow the transplant procedure lead to serious side effects. Furthermore, the pool of donor livers available for transplantation is far less than the demand. Well-characterized and physiologically relevant models of liver transplantation are crucial to a deeper understanding of the cellular processes governing the outcomes of liver transplantation and serve as a platform for testing new therapeutic strategies to enhance graft acceptance. Such a model has been found in the rat transplant model, which has an advantageous size for surgical procedures, similar postoperative immunological progression, and high genome match to the human liver. From rat liver transplant studies published in the last 5 years, it is clear that the rat model serves as a strong platform to elucidate transplant immunological mechanisms. Using the model, we have begun to uncover potential players and possible therapeutic targets to restore liver tolerance and preserve host immunocompetence. Here, we present an overview of recent literature for rat liver transplant models, with an aim to highlight the value of the models and to provide future perspectives on how these models could be further characterized to enhance the overall value of rat models to the field of liver transplantation.

摘要

对于许多终末期肝病患者来说,唯一的治疗选择是肝移植。然而,肝移植排斥反应在 24%-80%的移植患者中观察到,并且移植手术后需要终身服用药物,这会导致严重的副作用。此外,可供移植的供体肝脏数量远远少于需求。具有良好特征和生理相关性的肝移植模型对于更深入地了解控制肝移植结果的细胞过程至关重要,并且是测试增强移植物接受的新治疗策略的平台。在大鼠移植模型中发现了这样的模型,该模型的手术程序具有有利的大小、相似的术后免疫进展和与人类肝脏高度的基因组匹配。从过去 5 年发表的大鼠肝移植研究中可以清楚地看出,大鼠模型是阐明移植免疫机制的有力平台。使用该模型,我们已经开始发现潜在的参与者和可能的治疗靶点,以恢复肝脏耐受性并保持宿主免疫能力。在这里,我们对大鼠肝移植模型的最新文献进行了概述,旨在强调这些模型的价值,并提供未来的观点,即如何进一步对这些模型进行特征描述,以提高大鼠模型在肝移植领域的整体价值。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5c7/8376267/9c87e917b7aa/tp-105-1944-g001.jpg

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