Normothermic Machine Perfusion (NMP) Inhibits Proinflammatory Responses in the Liver and Promotes Regeneration

Jassem, W., Xystrakis, E., Ghnewa, Y.G., Yuksel, M., Pop, O., Martinez-Llordella, M., Jabri, Y., Huang, X., Lozano, J.J., Quaglia, A., Sanchez-Fueyo, A., Coussios, C.C., Rela, M., Friend, P., Heaton, N. and Ma, Y. 2019. Normothermic Machine Perfusion (NMP) Inhibits Proinflammatory Responses in the Liver and Promotes Regeneration. Hepatology. 70 (2), pp. 682-695. https://doi.org/10.1002/hep.30475

TitleNormothermic Machine Perfusion (NMP) Inhibits Proinflammatory Responses in the Liver and Promotes Regeneration
TypeJournal article
AuthorsJassem, W., Xystrakis, E., Ghnewa, Y.G., Yuksel, M., Pop, O., Martinez-Llordella, M., Jabri, Y., Huang, X., Lozano, J.J., Quaglia, A., Sanchez-Fueyo, A., Coussios, C.C., Rela, M., Friend, P., Heaton, N. and Ma, Y.
Abstract

Liver transplantation (LT) is a successful treatment for patients with liver failure. However, organ shortage results in over 11% of patients losing their chance of a transplant attributed to liver decompensation (LD) and death. Ischemia/reperfusion injury (IRI) following conventional cold storage (CS) is a major cause of injury leading to graft loss after LT. Normothermic machine perfusion (NMP), a method of organ preservation, provides oxygen and nutrition during preservation and allows aerobic metabolism. NMP has recently been shown to enable improved organ utilization and posttransplant outcomes following a phase I and a phase III randomized trial. The aim of the present study is to assess the impact of NMP on reducing IRI and to define the underlying mechanisms. We transplanted and compared 12 NMP with 27 CS‐preserved livers by performing gene microarray, immunoprofiling of hepatic lymphocytes, and immunochemistry staining of liver tissues for assessing necrosis, platelet deposition, and neutrophil infiltration, and the status of steatosis after NMP or CS prereperfusion and postreperfusion. Recipients receiving NMP grafts showed significantly lower peak aspartate aminotransferase (AST) levels than those receiving CS grafts. NMP altered gene‐expression profiles of liver tissue from proinflammation to prohealing and regeneration. NMP also reduced the number of interferon gamma (IFN‐γ) and interleukin (IL)‐17–producing T cells and enlarged the CD4posCD25highCD127negFOXP3pos regulatory T cell (Treg) pool. NMP liver tissues showed less necrosis and apoptosis in the parenchyma and fewer neutrophil infiltration compared to CS liver tissues. Conclusion: Reduced IRI in NMP recipients was the consequence of the combination of inhibiting inflammation and promoting graft regeneration.

JournalHepatology
Journal citation70 (2), pp. 682-695
ISSN1527-3350
Year2019
PublisherAmerican Association for the Study of Liver Diseases
Digital Object Identifier (DOI)https://doi.org/10.1002/hep.30475
Web address (URL)http://www.scopus.com/inward/record.url?eid=2-s2.0-85062967637&partnerID=MN8TOARS
Publication dates
PublishedAug 2019

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