Abstract

The most common preservation technique for liver grafts is static cold storage. Due to the organ shortage for liver transplantation (LT), extended criteria donor (ECD) allografts are increasingly used—despite the higher risk of inferior outcome after transplantation. Ex vivo liver machine perfusion (MP) has been developed to improve the outcome of transplantation, especially with ECD grafts, and is currently under evaluation in clinical trials. We performed a literature search on PubMed and ISI Web of Science to assemble an overview of rodent and porcine animal models of ex vivo liver MP for transplantation, which is essential for the present and future development of clinical liver MP. Hypothermic, subnormothermic, and normothermic MP systems have been successfully used for rat and pig LT. In comparison with hypothermic systems, normothermic perfusion often incorporates a dialysis unit. Moreover, it enables metabolic assessment of liver grafts. Allografts experiencing warm ischemic time have a superior survival rate after MP compared with cold storage alone, irrespective of the temperature used for perfusion. Furthermore, ex vivo MP improves the outcome of regular and ECD liver grafts in animal models. Small and large animal models of ex vivo liver MP are available to foster the further development of this new technology.

Impact Statement

Ex vivo machine perfusion is an important part of current research in the field of liver transplantation. While evidence for improve storage is constantly rising, the development of future applications such as quality assessment and therapeutic interventions necessitates robust animal models. This review is intended to provide an overview of this technology in common large and small animal models and to give an outlook on future applications. Moreover, we describe developmental steps that can be followed by others, and which can help to decrease the number of animals used for experiments based on the replace, reduce, refine concept.

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cover image Tissue Engineering Part B: Reviews
Tissue Engineering Part B: Reviews
Volume 29Issue Number 1February 2023
Pages: 10 - 27
PubMed: 35848526

History

Published online: 7 February 2023
Published in print: February 2023
Published ahead of print: 21 September 2022
Published ahead of production: 17 July 2022
Accepted: 17 May 2022
Received: 28 January 2022

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Vanessa Muth
Department of Surgery, Experimental Surgery, Charité—Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
Department of Surgery, Experimental Surgery, Charité—Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
Clinician Scientist Program, BIH Academy, Berlin Institute of Health at Charité—Universitätsmedizin Berlin, Berlin, Germany.
Simon Moosburner
Department of Surgery, Experimental Surgery, Charité—Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
Clinician Scientist Program, BIH Academy, Berlin Institute of Health at Charité—Universitätsmedizin Berlin, Berlin, Germany.
Department of Surgery, Experimental Surgery, Charité—Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
Julian Michelotto
Department of Surgery, Experimental Surgery, Charité—Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
Felix Strobl
Department of Surgery, Experimental Surgery, Charité—Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
Kristina Knaub
Department of Surgery, Experimental Surgery, Charité—Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
Cornelius Engelmann
Department of Hepatology and Gastroenterology, Charité—Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
Frank Tacke
Department of Hepatology and Gastroenterology, Charité—Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
Markus Selzner
Department of Surgery, Abdominal Transplant and HPB Surgery, Ajmera Family Transplant Centre, Toronto General Hospital, Toronto, Canada.
Johann Pratschke
Department of Surgery, Experimental Surgery, Charité—Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
Igor M. Sauer
Department of Surgery, Experimental Surgery, Charité—Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
Nathanael Raschzok [email protected]
Department of Surgery, Experimental Surgery, Charité—Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
Clinician Scientist Program, BIH Academy, Berlin Institute of Health at Charité—Universitätsmedizin Berlin, Berlin, Germany.

Notes

Address correspondence to: Nathanael Raschzok, MD, Department of Surgery, Experimental Surgery, Charité—Universitätsmedizin Berlin, Corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Campus Charité Mitte, Campus Virchow-Klinikum, Berlin, Germany [email protected]

Authors' Contributions

Conception and design of study: V.M., J.M.G.V.G., G.L., and N.R. Acquisition of data: V.M., J.M.G.V.G., S.M., J.M., F.S., K.K., and C.E. Analysis and interpretation of data: V.M., J.M.G.V.G., S.M., J.M., F.S., K.K., and C.E. Drafting of the article: V.M., J.M.G.V.G., G.L., J.P., I.M.S., and N.R. Revision of the article: V.M., J.M.G.V.G., G.L., F.T., M.S., J.P., I.M.S., and N.R.

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The authors declare no financial or competing interests.

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