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影响建立小鼠原位肝移植模型成功的细节因素。

Details determining the success in establishing a mouse orthotopic liver transplantation model.

机构信息

Department of Hepatobiliary and Pancreatic Surgery, The First Hospital of Jilin University, Changchun 130021, Jilin Province, China.

Key Laboratory of Organ Regeneration and Transplantation of Ministry of Education, The First Hospital of Jilin University, Changchun 130061, Jilin Province, China.

出版信息

World J Gastroenterol. 2020 Jul 21;26(27):3889-3898. doi: 10.3748/wjg.v26.i27.3889.

DOI:10.3748/wjg.v26.i27.3889
PMID:32774064
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7385559/
Abstract

Liver transplantation (LT) is currently the only effective treatment option for end-stage liver disease. The importance of animal models in transplantation is widely recognized among researchers. Because of the well-characterized mouse genome and the greater diversity and availability of both genetically modified animals and research reagents, mouse orthotopic LT (MOLT) has become an ideal model for the investigation of liver biology, tissue injury, regulation of alloimmunity and tolerance induction, and the pathogenesis of specific liver diseases. However, due to its complicated and technically demanding procedure, the model has merely been used by only a few research groups in the world for years. For a new learner, training lasting at least a couple of months or even years is required. Most of the investigators have emphasized the importance of elaborate techniques and dedicated instruments in establishing a MOLT model, but some details are often neglected. The nontechnical details are also significant, especially for researchers who have little experience in mouse microsurgery. Here, we review and summarize the crucial technical and nontechnical details in establishing the model of MOLT based on scientific articles and our experience in six aspects: animal selection, anesthesia, perioperative management, organ procurement, back-table preparation, and implantation surgery. We aim to enable research groups to shorten the learning curve and implement the mouse LT procedure with high technical success.

摘要

肝移植(LT)目前是治疗终末期肝病的唯一有效方法。研究人员广泛认识到动物模型在移植中的重要性。由于小鼠基因组特征明确,且遗传修饰动物和研究试剂的多样性和可用性更高,因此小鼠原位肝移植(MOLT)已成为研究肝脏生物学、组织损伤、同种异体免疫调节和诱导耐受以及特定肝脏疾病发病机制的理想模型。然而,由于其复杂且技术要求高的程序,该模型多年来仅被世界上少数几个研究小组使用。对于新学习者来说,至少需要几个月甚至几年的培训。大多数研究人员强调了在建立 MOLT 模型时精心设计技术和专用仪器的重要性,但有些细节往往被忽视。非技术细节也很重要,特别是对于在小鼠显微手术方面经验较少的研究人员。在这里,我们根据科学文章和我们在六个方面的经验,综述并总结了建立 MOLT 模型的关键技术和非技术细节:动物选择、麻醉、围手术期管理、器官获取、后台准备和植入手术。我们的目标是使研究小组能够缩短学习曲线,并以高技术成功率实施小鼠 LT 程序。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e007/7385559/70ff4207b946/WJG-26-3889-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e007/7385559/a6e3eb0988c6/WJG-26-3889-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e007/7385559/a77a205c7ff6/WJG-26-3889-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e007/7385559/70ff4207b946/WJG-26-3889-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e007/7385559/a6e3eb0988c6/WJG-26-3889-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e007/7385559/a77a205c7ff6/WJG-26-3889-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e007/7385559/70ff4207b946/WJG-26-3889-g003.jpg

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Biomed Pharmacother. 2020 Mar;123:109793. doi: 10.1016/j.biopha.2019.109793. Epub 2019 Dec 26.
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Graft-infiltrating PD-L1 cross-dressed dendritic cells regulate antidonor T cell responses in mouse liver transplant tolerance.嵌合浸润 PD-L1 的树突状细胞调节小鼠肝移植耐受中的抗供体 T 细胞反应。
Hepatology. 2018 Apr;67(4):1499-1515. doi: 10.1002/hep.29529. Epub 2018 Feb 18.
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Orthotopic liver transplantation from cardiac death donors in the mouse: a new model and evaluation of cardiac death time.
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Front Immunol. 2022 Jul 28;13:953240. doi: 10.3389/fimmu.2022.953240. eCollection 2022.
小鼠心脏死亡供体原位肝移植:一种新模型及心脏死亡时间评估
Iran J Basic Med Sci. 2017 Jun;20(6):683-689. doi: 10.22038/IJBMS.2017.8838.
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