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

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

doi:10.3791/57991

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Method Article

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

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DOI:

10.3791/57991

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October 6th, 2018

An Wang¹ , Isabel Jank¹ , Weiwei Wei¹ , Claudia Schindler¹ , Uta Dahmen¹

¹Experimental Transplantation Surgery, Department of General, Visceral and Vascular Surgery, University Hospital Jena

Summary

We establish a novel surgical technique for an in vivo single liver lobe perfusion model in rat as a prerequisite for further studying in vivo partial liver engineering in the future.

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.

Introduction

The indications for organ transplantation are constantly expanding. In contrast, organ donation rates and overall quality of organs are declining, leading to an increasing demand for grafts. The number of candidates added to the liver transplant waiting list continued to increase (e.g., in the United States, 11,340 patients were added in 2016, compared with 10,636 in 2015)¹. Despite substantial efforts, the number of available organs does not meet clinical needs. Due to the increased incidence of liver disease, many patients with end-stage liver diseases die on the transplant waiting list before a donor organ becomes available. To meet....