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Layer-by-layer heparinization of decellularized liver matrices to reduce thrombogenicity of tissue engineered grafts.对脱细胞肝基质进行逐层肝素化以降低组织工程移植物的血栓形成倾向。
J Clin Transl Res. 2015 Jul 19;1(1):48-56. doi: 10.18053/jctres.201501.004. eCollection 2015 Jul 20.
2
OPTN/SRTR 2016 Annual Data Report: Liver.OPTN/SRTR 2016 年度数据报告:肝脏。
Am J Transplant. 2018 Jan;18 Suppl 1:172-253. doi: 10.1111/ajt.14559.
3
Micropatterned co-culture of hepatocyte spheroids layered on non-parenchymal cells to understand heterotypic cellular interactions.将肝细胞球体微图案化共培养于非实质细胞上,以了解异型细胞间相互作用。
Sci Technol Adv Mater. 2013 Nov 13;14(6):065003. doi: 10.1088/1468-6996/14/6/065003. eCollection 2013 Dec.
4
In-vivo organ engineering: Perfusion of hepatocytes in a single liver lobe scaffold of living rats.体内器官工程:在活体大鼠的单个肝叶支架中灌注肝细胞。
Int J Biochem Cell Biol. 2016 Nov;80:124-131. doi: 10.1016/j.biocel.2016.10.003. Epub 2016 Oct 5.
5
Bioengineered Livers: A New Tool for Drug Testing and a Promising Solution to Meet the Growing Demand for Donor Organs.生物工程肝脏:药物测试的新工具以及满足对供体器官不断增长需求的有前景的解决方案。
Eur Surg Res. 2016;57(3-4):224-239. doi: 10.1159/000446211. Epub 2016 Jul 27.
6
Decellularized Liver Extracellular Matrix as Promising Tools for Transplantable Bioengineered Liver Promotes Hepatic Lineage Commitments of Induced Pluripotent Stem Cells.去细胞化肝脏细胞外基质作为可移植生物工程肝脏的有前景工具,可促进诱导多能干细胞向肝系细胞分化。
Tissue Eng Part A. 2016 Mar;22(5-6):449-60. doi: 10.1089/ten.TEA.2015.0313. Epub 2016 Feb 23.
7
Decellularization and Recellularization of Rat Livers With Hepatocytes and Endothelial Progenitor Cells.大鼠肝脏去细胞化及用肝细胞和内皮祖细胞进行再细胞化
Artif Organs. 2016 Mar;40(3):E25-38. doi: 10.1111/aor.12645. Epub 2015 Dec 4.
8
[Liver engineering as a new source of donor organs : A systematic review].[肝脏工程作为供体器官的新来源:一项系统综述]
Chirurg. 2016 Jun;87(6):504-13. doi: 10.1007/s00104-015-0015-y.
9
Optimizing perfusion-decellularization methods of porcine livers for clinical-scale whole-organ bioengineering.优化用于临床规模全器官生物工程的猪肝脏灌注脱细胞方法。
Biomed Res Int. 2015;2015:785474. doi: 10.1155/2015/785474. Epub 2015 Mar 31.
10
Recellularization of rat liver scaffolds by human liver stem cells.人肝干细胞对大鼠肝脏支架的再细胞化
Tissue Eng Part A. 2015 Jun;21(11-12):1929-39. doi: 10.1089/ten.TEA.2014.0573. Epub 2015 Apr 29.

一种新型手术技术作为大鼠体内部分肝脏工程的基础

A Novel Surgical Technique As a Foundation for In Vivo Partial Liver Engineering in Rat.

作者信息

Wang An, Jank Isabel, Wei Weiwei, Schindler Claudia, Dahmen Uta

机构信息

Experimental Transplantation Surgery, Department of General, Visceral and Vascular Surgery, University Hospital Jena.

Experimental Transplantation Surgery, Department of General, Visceral and Vascular Surgery, University Hospital Jena;

出版信息

J Vis Exp. 2018 Oct 6(140):57991. doi: 10.3791/57991.

DOI:10.3791/57991
PMID:30346385
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6235435/
Abstract

Organ engineering is a novel strategy to generate liver organ substitutes that can potentially be used in transplantation. Recently, in vivo liver engineering, including in vivo organ decellularization followed by repopulation, has emerged as a promising approach over ex vivo liver engineering. However, postoperative survival was not achieved. The aim of this study is to develop a novel surgical technique of in vivo selective liver lobe perfusion in rats as a prerequisite for in vivo liver engineering. We generate a circuit bypass only through the left lateral lobe. Then, the left lateral lobe is perfused with heparinized saline. The experiment is performed with 4 groups (n = 3 rats per group) based on different perfusion times of 20 min, 2 h, 3 h, and 4 h. Survival, as well as the macroscopically visible change of color and the histologically determined absence of blood cells in the portal triad and the sinusoids, is taken as an indicator for a successful model establishment. After selective perfusion of the left lateral lobe, we observe that the left lateral lobe, indeed, turned from red to faint yellow. In a histological assessment, no blood cells are visible in the branch of the portal vein, the central vein, and the sinusoids. The left lateral lobe turns red after reopening the blocked vessels. 12/12 rats survived the procedure for more than one week. We are the first to report a surgical model for in vivo single liver lobe perfusion with a long survival period of more than one week. In contrast to the previously published report, the most important advantage of the technique presented here is that perfusion of 70% of the liver is maintained throughout the whole procedure. The establishment of this technique provides a foundation for in vivo partial liver engineering in rats, including decellularization and recellularization.

摘要

器官工程是一种生成肝脏器官替代物的新策略,这些替代物有可能用于移植。最近,体内肝脏工程,包括体内器官去细胞化后再重新填充细胞,已成为一种比体外肝脏工程更有前景的方法。然而,术后存活并未实现。本研究的目的是开发一种大鼠体内选择性肝叶灌注的新手术技术,作为体内肝脏工程的前提条件。我们仅通过左外叶建立一个循环旁路。然后,用肝素化盐水灌注左外叶。根据20分钟、2小时、3小时和4小时的不同灌注时间,将实验分为4组(每组n = 3只大鼠)。将存活情况,以及肉眼可见的颜色变化和组织学确定的门静脉三联和肝血窦中无血细胞,作为成功建立模型的指标。在对左外叶进行选择性灌注后,我们观察到左外叶确实从红色变成了淡黄色。在组织学评估中,门静脉分支、中央静脉和肝血窦中均未见血细胞。重新开放阻塞血管后,左外叶恢复红色。12只大鼠全部存活超过一周。我们首次报道了一种体内单肝叶灌注的手术模型,其存活期超过一周。与之前发表的报告相比,这里介绍的技术最重要的优点是在整个过程中保持70%的肝脏灌注。该技术的建立为大鼠体内部分肝脏工程,包括去细胞化和再细胞化,奠定了基础。