Non-ischemic Heart Preservation via Hypothermic Cardioplegic Perfusion Induces Immunodepletion of Donor Hearts Resulting in Diminished Graft Infiltration Following Transplantation
Introduction: Many donor organs contain significant leukocyte reservoirs which upon transplantation activate recipient leukocytes to initiate acute rejection. We aimed to assess whether non-ischemic heart preservation via ex vivo perfusion promotes immunodepletion and alters the inflammatory status...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-07-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2020.01621/full |
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| author | William R. Critchley William R. Critchley John P. Stone John P. Stone Qiuming Liao Guangqi Qin Ivar Risnes Andrew Trafford Helge Scott Trygve Sjöberg Stig Steen James E. Fildes James E. Fildes |
| author_facet | William R. Critchley William R. Critchley John P. Stone John P. Stone Qiuming Liao Guangqi Qin Ivar Risnes Andrew Trafford Helge Scott Trygve Sjöberg Stig Steen James E. Fildes James E. Fildes |
| author_sort | William R. Critchley |
| collection | DOAJ |
| description | Introduction: Many donor organs contain significant leukocyte reservoirs which upon transplantation activate recipient leukocytes to initiate acute rejection. We aimed to assess whether non-ischemic heart preservation via ex vivo perfusion promotes immunodepletion and alters the inflammatory status of the donor organ prior to transplantation.Methods: Isolated porcine hearts underwent ex vivo hypothermic, cardioplegic perfusion for 8 h. Leukocyte populations were quantified in left ventricle samples by flow cytometry. Cell-free DNA, cytokines, and chemokines were quantified in the perfusate. Tissue integrity was profiled by targeted proteomics and a histological assessment was performed. Heterotopic transplants comparing ex vivo hypothermic preservation and static cold storage were utilized to assess graft infiltration as a solid clinical endpoint.Results:Ex vivo perfusion significantly immunodepleted myocardial tissue. The perfusate displayed a selective, pro-inflammatory cytokine/chemokine pattern dominated by IFN-γ. The tissue molecular profile was improved following perfusion by diminished expression of nine pro-apoptotic and six ischemia-associated proteins. Histologically, no evidence of tissue damage was observed and cardiac troponin I was low throughout perfusion. Cell-free DNA was detected, the source of which may be necrotic/apoptotic leukocytes. Post-transplant graft infiltration was markedly reduced in terms of both leucocyte distribution and intensity of foci.Conclusions: These findings demonstrate that ex vivo perfusion significantly reduced donor heart immunogenicity via loss of resident leukocytes. Despite the pro-inflammatory cytokine pattern observed, a pro-survival and reduced ischemia-related profile was observed, indicating an improvement in graft viability by perfusion. Diminished graft infiltration was observed in perfused hearts compared with those preserved by static cold storage following 48 h of transplantation. |
| first_indexed | 2024-12-13T09:30:23Z |
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| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-13T09:30:23Z |
| publishDate | 2020-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-6b325d67fdef4f73af1a01f9bfa6e2e82022-12-21T23:52:30ZengFrontiers Media S.A.Frontiers in Immunology1664-32242020-07-011110.3389/fimmu.2020.01621491358Non-ischemic Heart Preservation via Hypothermic Cardioplegic Perfusion Induces Immunodepletion of Donor Hearts Resulting in Diminished Graft Infiltration Following TransplantationWilliam R. Critchley0William R. Critchley1John P. Stone2John P. Stone3Qiuming Liao4Guangqi Qin5Ivar Risnes6Andrew Trafford7Helge Scott8Trygve Sjöberg9Stig Steen10James E. Fildes11James E. Fildes12The Ex-Vivo Lab, Division of Cell Matrix and Regenerative Medicine, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, School of Biological Sciences, The University of Manchester, Manchester, United KingdomThe Transplant Centre, Manchester University Hospitals NHS Foundation Trust, Manchester, United KingdomThe Ex-Vivo Lab, Division of Cell Matrix and Regenerative Medicine, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, School of Biological Sciences, The University of Manchester, Manchester, United KingdomThe Transplant Centre, Manchester University Hospitals NHS Foundation Trust, Manchester, United KingdomDepartment of Cardiothoracic Surgery, Lund University and Skåne University Hospital, Lund, SwedenDepartment of Cardiothoracic Surgery, Lund University and Skåne University Hospital, Lund, SwedenDepartment of Thoracic Surgery, Rikshospitalet, Oslo, NorwayDivision of Cardiovascular Sciences, University of Manchester, Manchester, United KingdomDepartment of Pathology, Institute of Clinical Medicine, University of Oslo, Oslo, NorwayDepartment of Cardiothoracic Surgery, Lund University and Skåne University Hospital, Lund, SwedenDepartment of Cardiothoracic Surgery, Lund University and Skåne University Hospital, Lund, SwedenThe Ex-Vivo Lab, Division of Cell Matrix and Regenerative Medicine, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, School of Biological Sciences, The University of Manchester, Manchester, United KingdomThe Transplant Centre, Manchester University Hospitals NHS Foundation Trust, Manchester, United KingdomIntroduction: Many donor organs contain significant leukocyte reservoirs which upon transplantation activate recipient leukocytes to initiate acute rejection. We aimed to assess whether non-ischemic heart preservation via ex vivo perfusion promotes immunodepletion and alters the inflammatory status of the donor organ prior to transplantation.Methods: Isolated porcine hearts underwent ex vivo hypothermic, cardioplegic perfusion for 8 h. Leukocyte populations were quantified in left ventricle samples by flow cytometry. Cell-free DNA, cytokines, and chemokines were quantified in the perfusate. Tissue integrity was profiled by targeted proteomics and a histological assessment was performed. Heterotopic transplants comparing ex vivo hypothermic preservation and static cold storage were utilized to assess graft infiltration as a solid clinical endpoint.Results:Ex vivo perfusion significantly immunodepleted myocardial tissue. The perfusate displayed a selective, pro-inflammatory cytokine/chemokine pattern dominated by IFN-γ. The tissue molecular profile was improved following perfusion by diminished expression of nine pro-apoptotic and six ischemia-associated proteins. Histologically, no evidence of tissue damage was observed and cardiac troponin I was low throughout perfusion. Cell-free DNA was detected, the source of which may be necrotic/apoptotic leukocytes. Post-transplant graft infiltration was markedly reduced in terms of both leucocyte distribution and intensity of foci.Conclusions: These findings demonstrate that ex vivo perfusion significantly reduced donor heart immunogenicity via loss of resident leukocytes. Despite the pro-inflammatory cytokine pattern observed, a pro-survival and reduced ischemia-related profile was observed, indicating an improvement in graft viability by perfusion. Diminished graft infiltration was observed in perfused hearts compared with those preserved by static cold storage following 48 h of transplantation.https://www.frontiersin.org/article/10.3389/fimmu.2020.01621/fullheart transplantationacute rejectionheart preservationhypothermic cardioplegic ex vivo heart perfusionpassenger leukocytes |
| spellingShingle | William R. Critchley William R. Critchley John P. Stone John P. Stone Qiuming Liao Guangqi Qin Ivar Risnes Andrew Trafford Helge Scott Trygve Sjöberg Stig Steen James E. Fildes James E. Fildes Non-ischemic Heart Preservation via Hypothermic Cardioplegic Perfusion Induces Immunodepletion of Donor Hearts Resulting in Diminished Graft Infiltration Following Transplantation Frontiers in Immunology heart transplantation acute rejection heart preservation hypothermic cardioplegic ex vivo heart perfusion passenger leukocytes |
| title | Non-ischemic Heart Preservation via Hypothermic Cardioplegic Perfusion Induces Immunodepletion of Donor Hearts Resulting in Diminished Graft Infiltration Following Transplantation |
| title_full | Non-ischemic Heart Preservation via Hypothermic Cardioplegic Perfusion Induces Immunodepletion of Donor Hearts Resulting in Diminished Graft Infiltration Following Transplantation |
| title_fullStr | Non-ischemic Heart Preservation via Hypothermic Cardioplegic Perfusion Induces Immunodepletion of Donor Hearts Resulting in Diminished Graft Infiltration Following Transplantation |
| title_full_unstemmed | Non-ischemic Heart Preservation via Hypothermic Cardioplegic Perfusion Induces Immunodepletion of Donor Hearts Resulting in Diminished Graft Infiltration Following Transplantation |
| title_short | Non-ischemic Heart Preservation via Hypothermic Cardioplegic Perfusion Induces Immunodepletion of Donor Hearts Resulting in Diminished Graft Infiltration Following Transplantation |
| title_sort | non ischemic heart preservation via hypothermic cardioplegic perfusion induces immunodepletion of donor hearts resulting in diminished graft infiltration following transplantation |
| topic | heart transplantation acute rejection heart preservation hypothermic cardioplegic ex vivo heart perfusion passenger leukocytes |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2020.01621/full |
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