Improving Liver Graft Function Using CD47 Blockade in the Setting of Normothermic Machine Perfusion.

Autor:	Garcia-Aroz S; Department of Surgery, Washington University School of Medicine, St. Louis, MO., Xu M; Department of Surgery, Washington University School of Medicine, St. Louis, MO., Ahmed O; Department of Surgery, Washington University School of Medicine, St. Louis, MO., Hollingshead J; Department of Surgery, Washington University School of Medicine, St. Louis, MO., Wang X; Department of Surgery, Washington University School of Medicine, St. Louis, MO.; Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, China., Banan B; Department of Surgery, Washington University School of Medicine, St. Louis, MO., Khan A; Department of Surgery, Washington University School of Medicine, St. Louis, MO., Kang LI; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO., Zhang Z; Department of Surgery, Washington University School of Medicine, St. Louis, MO., Upadhya G; Department of Surgery, Washington University School of Medicine, St. Louis, MO., Manning P; Arch Oncology, Inc., St. Louis, MO., Lin Y; Department of Surgery, Washington University School of Medicine, St. Louis, MO., Chapman WC; Department of Surgery, Washington University School of Medicine, St. Louis, MO.
Jazyk:	angličtina
Zdroj:	Transplantation [Transplantation] 2022 Jan 01; Vol. 106 (1), pp. 37-47.
DOI:	10.1097/TP.0000000000003688
Abstrakt:	Background: Toward the goal of using more livers for transplantation, transplant centers are looking to increase the use of organs from "marginal" donors. Livers from these donors, however, have been shown to be more susceptible to preservation and reperfusion injury. Methods: Using a porcine model of donation after circulatory death, we studied the use of antibody-mediated CD47 blockade to further improve liver graft function undergoing normothermic machine perfusion. Livers from 20 pigs (5 per group) were brought under either 30 or 60 min of warm ischemia time followed by the administration of CD47 monoclonal antibody (CD47mAb) treatment or immunoglobulin G control antibodies and 6 h of normothermic extracorporeal liver perfusion. Results: After 6 h of normothermic extracorporeal liver perfusion, CD47mAb-treated livers with 30 or 60 min warm ischemia time had significantly lower alanine transaminase levels and higher bile production compared with their respective control groups. Blockade of the CD47 signaling pathway resulted in significantly lower thrombospondin-1 protein levels, lower expression of caspase-3, and higher expression of phosphorylated extracellular signal-regulated kinase. Conclusions: These findings suggested that CD47mAb treatment decreases ischemia/reperfusion injury through CD47/thrombospondin-1 signaling downregulation and the presence of necrosis/apoptosis after reperfusion and could increase liver regeneration during normothermic perfusion of the liver. Competing Interests: W.C.C. is a founder of Pathfinder Therapeutics and an advisory board member of Novartis Pharmaceutical. P.M. is an employee and stockholder of Arch Oncology. The other authors declare no conflicts of interest. (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)
Databáze:	MEDLINE
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