Organ Restoration With Normothermic Machine Perfusion and Immune Reaction
Liver transplantation is the only recognized effective treatment for end-stage liver disease. However, organ shortages have become the main challenge for patients and physicians within the transplant community. Waiting list mortality remains an issue with around 10% of patients dying whilst waiting...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-10-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2020.565616/full |
| _version_ | 1818879412308803584 |
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| author | Alessandro Parente Daniel-Clement Osei-Bordom Daniel-Clement Osei-Bordom Daniel-Clement Osei-Bordom Vincenzo Ronca Vincenzo Ronca Vincenzo Ronca M. Thamara P. R. Perera Darius Mirza Darius Mirza |
| author_facet | Alessandro Parente Daniel-Clement Osei-Bordom Daniel-Clement Osei-Bordom Daniel-Clement Osei-Bordom Vincenzo Ronca Vincenzo Ronca Vincenzo Ronca M. Thamara P. R. Perera Darius Mirza Darius Mirza |
| author_sort | Alessandro Parente |
| collection | DOAJ |
| description | Liver transplantation is the only recognized effective treatment for end-stage liver disease. However, organ shortages have become the main challenge for patients and physicians within the transplant community. Waiting list mortality remains an issue with around 10% of patients dying whilst waiting for an available organ. The post-transplantation period is also associated with an adverse complication rate for these specific cohorts of high-risk patients, particularly regarding patient and graft survival. Ischaemia reperfusion injury (IRI) has been highlighted as the mechanism of injury that increases parenchymal damage, which eventually lead to significant graft dysfunction and other poor outcome indicators. The consequences of IRI in clinical practice such as reperfusion syndrome, primary non-function of graft, allograft dysfunction, ischaemic biliary damage and early biliary complications can be life-threatening. IRI dictates the development of a significant inflammatory response that drives the pathway to eventual cell death. The main mechanisms of IRI are mitochondrial damage due to low oxygen tension within the hepatic micro-environment and severe adenosine triphosphate (ATP) depletion during the ischaemic period. After the restoration of normal blood flow, this damage is further enhanced by reoxygenation as the mitochondria respond to reperfusion by releasing reactive oxygen species (ROS), which in turn activate Kupffer cells within the hepatic micro-environment, leading to a pro-inflammatory response and eventual parenchymal cell apoptosis and associated tissue degradation. Machine perfusion (MP) is one emergent strategy considered to be one of the most important advances in organ preservation, restoration and transplantation. Indeed, MP has the potential to rescue frequently discarded organs and has been shown to limit the extent of IRI, leading to suppression of the deleterious pro-inflammatory response. This immunomodulation reduces the prevalence of allograft rejection, the use of immunosuppression therapy and minimizes post-transplant complications. This review aims to update the current knowledge of MP with a focus on normothermic machine liver perfusion (NMLP) and its potential role in immune response pathways. |
| first_indexed | 2024-12-19T14:29:40Z |
| format | Article |
| id | doaj.art-dcb2a04690464fb19eb7f17957d93050 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-19T14:29:40Z |
| publishDate | 2020-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-dcb2a04690464fb19eb7f17957d930502022-12-21T20:17:30ZengFrontiers Media S.A.Frontiers in Immunology1664-32242020-10-011110.3389/fimmu.2020.565616565616Organ Restoration With Normothermic Machine Perfusion and Immune ReactionAlessandro Parente0Daniel-Clement Osei-Bordom1Daniel-Clement Osei-Bordom2Daniel-Clement Osei-Bordom3Vincenzo Ronca4Vincenzo Ronca5Vincenzo Ronca6M. Thamara P. R. Perera7Darius Mirza8Darius Mirza9Liver Unit, Queen Elizabeth Hospital, University Hospitals Birmingham NHS Foundation Trust, Birmingham, United KingdomLiver Unit, Queen Elizabeth Hospital, University Hospitals Birmingham NHS Foundation Trust, Birmingham, United KingdomCentre for Liver and Gastrointestinal Research, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, United KingdomNational Institute for Health Research Birmingham Liver Biomedical Research Centre, University Hospitals Birmingham National Health Service Foundation Trust, Birmingham, United KingdomLiver Unit, Queen Elizabeth Hospital, University Hospitals Birmingham NHS Foundation Trust, Birmingham, United KingdomCentre for Liver and Gastrointestinal Research, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, United KingdomDivision of Gastroenterology and Centre for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milan Bicocca, Milan, ItalyLiver Unit, Queen Elizabeth Hospital, University Hospitals Birmingham NHS Foundation Trust, Birmingham, United KingdomLiver Unit, Queen Elizabeth Hospital, University Hospitals Birmingham NHS Foundation Trust, Birmingham, United KingdomCentre for Liver and Gastrointestinal Research, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, United KingdomLiver transplantation is the only recognized effective treatment for end-stage liver disease. However, organ shortages have become the main challenge for patients and physicians within the transplant community. Waiting list mortality remains an issue with around 10% of patients dying whilst waiting for an available organ. The post-transplantation period is also associated with an adverse complication rate for these specific cohorts of high-risk patients, particularly regarding patient and graft survival. Ischaemia reperfusion injury (IRI) has been highlighted as the mechanism of injury that increases parenchymal damage, which eventually lead to significant graft dysfunction and other poor outcome indicators. The consequences of IRI in clinical practice such as reperfusion syndrome, primary non-function of graft, allograft dysfunction, ischaemic biliary damage and early biliary complications can be life-threatening. IRI dictates the development of a significant inflammatory response that drives the pathway to eventual cell death. The main mechanisms of IRI are mitochondrial damage due to low oxygen tension within the hepatic micro-environment and severe adenosine triphosphate (ATP) depletion during the ischaemic period. After the restoration of normal blood flow, this damage is further enhanced by reoxygenation as the mitochondria respond to reperfusion by releasing reactive oxygen species (ROS), which in turn activate Kupffer cells within the hepatic micro-environment, leading to a pro-inflammatory response and eventual parenchymal cell apoptosis and associated tissue degradation. Machine perfusion (MP) is one emergent strategy considered to be one of the most important advances in organ preservation, restoration and transplantation. Indeed, MP has the potential to rescue frequently discarded organs and has been shown to limit the extent of IRI, leading to suppression of the deleterious pro-inflammatory response. This immunomodulation reduces the prevalence of allograft rejection, the use of immunosuppression therapy and minimizes post-transplant complications. This review aims to update the current knowledge of MP with a focus on normothermic machine liver perfusion (NMLP) and its potential role in immune response pathways.https://www.frontiersin.org/articles/10.3389/fimmu.2020.565616/fullnormothermic machine liver perfusionimmune activationhepatic microenvironmentgraft survivalliver transplantation |
| spellingShingle | Alessandro Parente Daniel-Clement Osei-Bordom Daniel-Clement Osei-Bordom Daniel-Clement Osei-Bordom Vincenzo Ronca Vincenzo Ronca Vincenzo Ronca M. Thamara P. R. Perera Darius Mirza Darius Mirza Organ Restoration With Normothermic Machine Perfusion and Immune Reaction Frontiers in Immunology normothermic machine liver perfusion immune activation hepatic microenvironment graft survival liver transplantation |
| title | Organ Restoration With Normothermic Machine Perfusion and Immune Reaction |
| title_full | Organ Restoration With Normothermic Machine Perfusion and Immune Reaction |
| title_fullStr | Organ Restoration With Normothermic Machine Perfusion and Immune Reaction |
| title_full_unstemmed | Organ Restoration With Normothermic Machine Perfusion and Immune Reaction |
| title_short | Organ Restoration With Normothermic Machine Perfusion and Immune Reaction |
| title_sort | organ restoration with normothermic machine perfusion and immune reaction |
| topic | normothermic machine liver perfusion immune activation hepatic microenvironment graft survival liver transplantation |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2020.565616/full |
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