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      Pushing the boundaries of innovation: the potential of ex vivo organ perfusion from an interdisciplinary point of view

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          Abstract

          Ex vivo machine perfusion (EVMP) is an emerging technique for preserving explanted solid organs with primary application in allogeneic organ transplantation. EVMP has been established as an alternative to the standard of care static-cold preservation, allowing for prolonged preservation and real-time monitoring of organ quality while reducing/preventing ischemia–reperfusion injury. Moreover, it has paved the way to involve expanded criteria donors, e.g., after circulatory death, thus expanding the donor organ pool. Ongoing improvements in EVMP protocols, especially expanding the duration of preservation, paved the way for its broader application, in particular for reconditioning and modification of diseased organs and tumor and infection therapies and regenerative approaches. Moreover, implementing EVMP for in vivo-like preclinical studies improving disease modeling raises significant interest, while providing an ideal interface for bioengineering and genetic manipulation. These approaches can be applied not only in an allogeneic and xenogeneic transplant setting but also in an autologous setting, where patients can be on temporary organ support while the diseased organs are treated ex vivo, followed by reimplantation of the cured organ. This review provides a comprehensive overview of the differences and similarities in abdominal (kidney and liver) and thoracic (lung and heart) EVMP, focusing on the organ-specific components and preservation techniques, specifically on the composition of perfusion solutions and their supplements and perfusion temperatures and flow conditions. Novel treatment opportunities beyond organ transplantation and limitations of abdominal and thoracic EVMP are delineated to identify complementary interdisciplinary approaches for the application and development of this technique.

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          Most cited references211

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          Nusinersen versus Sham Control in Infantile-Onset Spinal Muscular Atrophy

          New England Journal of Medicine, 377(18), 1723-1732
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            Incidence and outcomes of acute lung injury.

            Acute lung injury is a critical illness syndrome consisting of acute hypoxemic respiratory failure with bilateral pulmonary infiltrates that are not attributed to left atrial hypertension. Despite recent advances in our understanding of the mechanism and treatment of acute lung injury, its incidence and outcomes in the United States have been unclear. We conducted a prospective, population-based, cohort study in 21 hospitals in and around King County, Washington, from April 1999 through July 2000, using a validated screening protocol to identify patients who met the consensus criteria for acute lung injury. A total of 1113 King County residents undergoing mechanical ventilation met the criteria for acute lung injury and were 15 years of age or older. On the basis of this figure, the crude incidence of acute lung injury was 78.9 per 100,000 person-years and the age-adjusted incidence was 86.2 per 100,000 person-years. The in-hospital mortality rate was 38.5 percent. The incidence of acute lung injury increased with age from 16 per 100,000 person-years for those 15 through 19 years of age to 306 per 100,000 person-years for those 75 through 84 years of age. Mortality increased with age from 24 percent for patients 15 through 19 years of age to 60 percent for patients 85 years of age or older (P<0.001). We estimate that each year in the United States there are 190,600 cases of acute lung injury, which are associated with 74,500 deaths and 3.6 million hospital days. Acute lung injury has a substantial impact on public health, with an incidence in the United States that is considerably higher than previous reports have suggested. Copyright 2005 Massachusetts Medical Society.
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              A randomized trial of normothermic preservation in liver transplantation

              Liver transplantation is a highly successful treatment, but is severely limited by the shortage in donor organs. However, many potential donor organs cannot be used; this is because sub-optimal livers do not tolerate conventional cold storage and there is no reliable way to assess organ viability preoperatively. Normothermic machine perfusion maintains the liver in a physiological state, avoids cooling and allows recovery and functional testing. Here we show that, in a randomized trial with 220 liver transplantations, compared to conventional static cold storage, normothermic preservation is associated with a 50% lower level of graft injury, measured by hepatocellular enzyme release, despite a 50% lower rate of organ discard and a 54% longer mean preservation time. There was no significant difference in bile duct complications, graft survival or survival of the patient. If translated to clinical practice, these results would have a major impact on liver transplant outcomes and waiting list mortality.
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                Author and article information

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                Journal
                Front Cardiovasc Med
                Front Cardiovasc Med
                Front. Cardiovasc. Med.
                Frontiers in Cardiovascular Medicine
                Frontiers Media S.A.
                2297-055X
                12 October 2023
                2023
                : 10
                : 1272945
                Affiliations
                [ 1 ]Department of Cardiothoracic Surgery, Deutsches Herzzentrum der Charité , Berlin, Germany
                [ 2 ]Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin , Berlin, Germany
                [ 3 ]Department of General, Visceral and Transplant Surgery, Hannover Medical School , Hannover, Germany
                [ 4 ]Division of Transplant Surgery, Department of Surgery, Brigham and Women’s Hospital and Harvard Medical School , Boston, MA, United States
                [ 5 ]Division of Plastic Surgery, Department of Surgery, Brigham and Women’s Hospital and Harvard Medical School , Boston, MA, United States
                [ 6 ]Department of Plastic Surgery and Hand Surgery, Klinikum Rechts der Isar, Technical University of Munich , Munich, Germany
                [ 7 ]Department for Cardiothoracic, Transplantation and Vascular Surgery, Hannover Medical School , Hannover, Germany
                [ 8 ]German Center for Lung Research (DZL) , Hannover, Germany
                [ 9 ]Lower Saxony Center for Biomedical Engineering, Implant Research and Development (NIFE) , Hannover, Germany
                [ 10 ]DZHK (German Centre for Cardiovascular Research), Partner Site , Berlin, Germany
                [ 11 ]Department of Health Science and Technology, Translational Cardiovascular Technology, ETH Zurich , Zürich, Switzerland
                Author notes

                Edited by: Cristiano Amarelli, Monaldi, Azienda dei Colli, Italy

                Reviewed by: Andrea Lechiancole, Azienda Sanitaria Universitaria Friuli Centrale (ASU FC), Italy Peter Simon Macdonald, St Vincent’s Hospital (Melbourne), Australia

                [* ] Correspondence: Bettina Wiegmann wiegmann.bettina@ 123456mh-hannover.de
                [ † ]

                These authors have contributed equally to this work

                Article
                10.3389/fcvm.2023.1272945
                10602690
                37900569
                a871bd34-c584-4614-9cc8-57957287913e
                © 2023 Iske, Schroeter, Knoedler, Nazari-Shafti, Wert, Roesel, Hennig, Niehaus, Kuehn, Ius, Falk, Schmelzle, Ruhparwar, Haverich, Knosalla, Tullius, Vondran and Wiegmann.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 04 August 2023
                : 22 September 2023
                Page count
                Figures: 2, Tables: 2, Equations: 0, References: 211, Pages: 0, Words: 0
                Funding
                The authors declare that no financial support was received for the research, authorship, and/or publication of this article.
                Categories
                Cardiovascular Medicine
                Review
                Custom metadata
                Heart Failure and Transplantation

                transplantation,transplantation heart,ex vivo organ perfusion,machine perfusion,ex vivo machine perfusion,organ modification,ex vivo surgery

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