Ex-vivo perfusion describes the extra-corporeal delivery of fluid to an organ or tissue. Although it has been widely studied in the context of organ preservation and transplantation, it has also proven to be an invaluable tool in the development of novel models for translational pre-clinical research. Here, we review the literature reporting ex-vivo human liver perfusion experiments to further understand current perfusion techniques and protocols together with their applications. A computerised search was made of Ovid, MEDLINE, and Embase using the search words "ex-vivo liver or hepatic perfusion". All relevant studies in English describing experiments using ex-vivo perfusion of human livers between 2016 and 2021, inclusive, were included. Of 21 reviewed studies, 19 used ex-vivo human liver perfusion in the context of allogeneic liver transplantation. The quality and size of the studies varied considerably. Human liver perfusion was almost exclusively limited to whole organs and "split" livers, although one study did describe the successful perfusion of tissue sections following a partial hepatectomy. This review of recent literature involving exvivo human liver perfusion demonstrates that the technique is not limited to whole liver perfusion. Splitliver perfusion is extremely valuable allowing one lobe to act as a control and increasing the number available for research. This review also highlights the present lack of any reports of segmental liver perfusion. The discarded donor liver is a scarce resource, and the successful use of segmental perfusion has the potential to expand the available experimental models to facilitate pre-clinical experimentation.
IntroductionEx vivo machine perfusion describes the technique where organs are continuously perfused and oxygenated extracorporeally (at physiological conditions) to maintain the organs' viability. To our knowledge, there are currently no reported studies describing ex vivo perfusion of a single hepatic segment. Here, we describe the development of a porcine ex vivo hepatic segmental perfusion model to demonstrate proof of concept and support further research into the ex vivo perfusion of the human liver using discarded tissue. MethodsWhole livers were retrieved from abattoir-derived pigs and connected to a normothermic extracorporeal perfusion circuit. Constant segmental perfusion via the common or segmental hepatic artery and portal vein with heparinised autologous blood was established. The viability of the perfused organ was assessed by monitoring perfusion pressures, flow rates and histology samples. ResultsFollowing perfusion and optimisation of the model for three hepatic segments, the third perfusion demonstrated viable hepatocytes centrally after 4 h of segmental perfusion. ConclusionEx vivo hepatic segmental perfusion is technically challenging but its success in a porcine model and the principles learned should facilitate the development of an analogous human model using discarded tissue following formal liver resections. The model would use a healthy liver segment following a major formal resection such as a hemi-hepatectomy and ex vivo perfusion performed via a segmental hepatic artery and portal vein. If successful this model would represent a significant development and enable ethical translation research to assess the response of human livers to a variety of stressors, including toxicity and infection.
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