Proteomic changes to immune and inflammatory processes underlie lung preservation using ex vivo cytokine adsorption

IntroductionIn recent years, the field of graft preservation has made considerable strides in improving outcomes related to solid organ restoration and regeneration. Ex vivo lung perfusion (EVLP) in line with the related devices and treatments has yielded promising results within preclinical and cli...

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Main Authors: Anna Niroomand, Gabriel Hirdman, Leif Pierre, Haider Ghaidan, Sven Kjellström, Martin Stenlo, Snejana Hyllén, Franziska Olm, Sandra Lindstedt
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-10-01
Series:Frontiers in Cardiovascular Medicine
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fcvm.2023.1274444/full
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author Anna Niroomand
Anna Niroomand
Anna Niroomand
Gabriel Hirdman
Gabriel Hirdman
Gabriel Hirdman
Leif Pierre
Leif Pierre
Leif Pierre
Leif Pierre
Haider Ghaidan
Haider Ghaidan
Haider Ghaidan
Haider Ghaidan
Sven Kjellström
Martin Stenlo
Martin Stenlo
Martin Stenlo
Martin Stenlo
Martin Stenlo
Snejana Hyllén
Snejana Hyllén
Snejana Hyllén
Snejana Hyllén
Franziska Olm
Franziska Olm
Franziska Olm
Sandra Lindstedt
Sandra Lindstedt
Sandra Lindstedt
Sandra Lindstedt
author_facet Anna Niroomand
Anna Niroomand
Anna Niroomand
Gabriel Hirdman
Gabriel Hirdman
Gabriel Hirdman
Leif Pierre
Leif Pierre
Leif Pierre
Leif Pierre
Haider Ghaidan
Haider Ghaidan
Haider Ghaidan
Haider Ghaidan
Sven Kjellström
Martin Stenlo
Martin Stenlo
Martin Stenlo
Martin Stenlo
Martin Stenlo
Snejana Hyllén
Snejana Hyllén
Snejana Hyllén
Snejana Hyllén
Franziska Olm
Franziska Olm
Franziska Olm
Sandra Lindstedt
Sandra Lindstedt
Sandra Lindstedt
Sandra Lindstedt
author_sort Anna Niroomand
collection DOAJ
description IntroductionIn recent years, the field of graft preservation has made considerable strides in improving outcomes related to solid organ restoration and regeneration. Ex vivo lung perfusion (EVLP) in line with the related devices and treatments has yielded promising results within preclinical and clinical studies, with the potential to improve graft quality. Its main benefit is to render marginal and declined donor lungs suitable for transplantation, ultimately increasing the donor pool available for transplantation. In addition, using such therapies in machine perfusion could also increase preservation time, facilitating logistical planning. Cytokine adsorption has been demonstrated as a potentially safe and effective therapy when applied to the EVLP circuit and post-transplantation. However, the mechanism by which this therapy improves the donor lung on a molecular basis is not yet fully understood.MethodsWe hypothesized that there were characteristic inflammatory and immunomodulatory differences between the lungs treated with and without cytokine adsorption, reflecting proteomic changes in the gene ontology pathways and across inflammation-related proteins. In this study, we investigate the molecular mechanisms and signaling pathways of how cytokine adsorption impacts lung function when used during EVLP and post-transplantation as hemoperfusion in a porcine model. Lung tissues during EVLP and post-lung transplantation were analyzed for their proteomic profiles using mass spectrometry.ResultsWe found through gene set enrichment analysis that the inflammatory and immune processes and coagulation pathways were significantly affected by the cytokine treatment after EVLP and transplantation.ConclusionIn conclusion, we showed that the molecular mechanisms are using a proteomic approach behind the previously reported effects of cytokine adsorption when compared to the non-treated transplant recipients undergoing EVLP.
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spelling doaj.art-0c18bde4a0984ac99968f1835ed2af0d2023-10-03T04:34:35ZengFrontiers Media S.A.Frontiers in Cardiovascular Medicine2297-055X2023-10-011010.3389/fcvm.2023.12744441274444Proteomic changes to immune and inflammatory processes underlie lung preservation using ex vivo cytokine adsorptionAnna Niroomand0Anna Niroomand1Anna Niroomand2Gabriel Hirdman3Gabriel Hirdman4Gabriel Hirdman5Leif Pierre6Leif Pierre7Leif Pierre8Leif Pierre9Haider Ghaidan10Haider Ghaidan11Haider Ghaidan12Haider Ghaidan13Sven Kjellström14Martin Stenlo15Martin Stenlo16Martin Stenlo17Martin Stenlo18Martin Stenlo19Snejana Hyllén20Snejana Hyllén21Snejana Hyllén22Snejana Hyllén23Franziska Olm24Franziska Olm25Franziska Olm26Sandra Lindstedt27Sandra Lindstedt28Sandra Lindstedt29Sandra Lindstedt30Department of Clinical Sciences, Lund University, Lund, SwedenLund Stem Cell Center, Lund University, Lund, SwedenSchool of Medicine, Rutgers Robert Wood Johnson University, New Brunswick, NJ, United StatesDepartment of Clinical Sciences, Lund University, Lund, SwedenLund Stem Cell Center, Lund University, Lund, SwedenWallenberg Center for Molecular Medicine, Lund University, Lund, SwedenDepartment of Clinical Sciences, Lund University, Lund, SwedenLund Stem Cell Center, Lund University, Lund, SwedenWallenberg Center for Molecular Medicine, Lund University, Lund, SwedenDepartment of Cardiothoracic Surgery and Transplantation, Skåne University Hospital, Lund, SwedenDepartment of Clinical Sciences, Lund University, Lund, SwedenLund Stem Cell Center, Lund University, Lund, SwedenWallenberg Center for Molecular Medicine, Lund University, Lund, SwedenDepartment of Cardiothoracic Surgery and Transplantation, Skåne University Hospital, Lund, SwedenDepartment of Clinical Sciences, BioMS, Lund University, Lund, SwedenDepartment of Clinical Sciences, Lund University, Lund, SwedenLund Stem Cell Center, Lund University, Lund, SwedenWallenberg Center for Molecular Medicine, Lund University, Lund, SwedenDepartment of Cardiothoracic Surgery and Transplantation, Skåne University Hospital, Lund, SwedenDepartment of Cardiothoracic Anesthesia and Intensive Care, Skåne University Hospital, Lund, SwedenDepartment of Clinical Sciences, Lund University, Lund, SwedenLund Stem Cell Center, Lund University, Lund, SwedenWallenberg Center for Molecular Medicine, Lund University, Lund, SwedenDepartment of Cardiothoracic Anesthesia and Intensive Care, Skåne University Hospital, Lund, SwedenDepartment of Clinical Sciences, Lund University, Lund, SwedenLund Stem Cell Center, Lund University, Lund, SwedenWallenberg Center for Molecular Medicine, Lund University, Lund, SwedenDepartment of Clinical Sciences, Lund University, Lund, SwedenLund Stem Cell Center, Lund University, Lund, SwedenWallenberg Center for Molecular Medicine, Lund University, Lund, SwedenDepartment of Cardiothoracic Surgery and Transplantation, Skåne University Hospital, Lund, SwedenIntroductionIn recent years, the field of graft preservation has made considerable strides in improving outcomes related to solid organ restoration and regeneration. Ex vivo lung perfusion (EVLP) in line with the related devices and treatments has yielded promising results within preclinical and clinical studies, with the potential to improve graft quality. Its main benefit is to render marginal and declined donor lungs suitable for transplantation, ultimately increasing the donor pool available for transplantation. In addition, using such therapies in machine perfusion could also increase preservation time, facilitating logistical planning. Cytokine adsorption has been demonstrated as a potentially safe and effective therapy when applied to the EVLP circuit and post-transplantation. However, the mechanism by which this therapy improves the donor lung on a molecular basis is not yet fully understood.MethodsWe hypothesized that there were characteristic inflammatory and immunomodulatory differences between the lungs treated with and without cytokine adsorption, reflecting proteomic changes in the gene ontology pathways and across inflammation-related proteins. In this study, we investigate the molecular mechanisms and signaling pathways of how cytokine adsorption impacts lung function when used during EVLP and post-transplantation as hemoperfusion in a porcine model. Lung tissues during EVLP and post-lung transplantation were analyzed for their proteomic profiles using mass spectrometry.ResultsWe found through gene set enrichment analysis that the inflammatory and immune processes and coagulation pathways were significantly affected by the cytokine treatment after EVLP and transplantation.ConclusionIn conclusion, we showed that the molecular mechanisms are using a proteomic approach behind the previously reported effects of cytokine adsorption when compared to the non-treated transplant recipients undergoing EVLP.https://www.frontiersin.org/articles/10.3389/fcvm.2023.1274444/fulllung transplantationmass spectrometryex vivo lung perfusioncytokine adsorptionproteomics
spellingShingle Anna Niroomand
Anna Niroomand
Anna Niroomand
Gabriel Hirdman
Gabriel Hirdman
Gabriel Hirdman
Leif Pierre
Leif Pierre
Leif Pierre
Leif Pierre
Haider Ghaidan
Haider Ghaidan
Haider Ghaidan
Haider Ghaidan
Sven Kjellström
Martin Stenlo
Martin Stenlo
Martin Stenlo
Martin Stenlo
Martin Stenlo
Snejana Hyllén
Snejana Hyllén
Snejana Hyllén
Snejana Hyllén
Franziska Olm
Franziska Olm
Franziska Olm
Sandra Lindstedt
Sandra Lindstedt
Sandra Lindstedt
Sandra Lindstedt
Proteomic changes to immune and inflammatory processes underlie lung preservation using ex vivo cytokine adsorption
Frontiers in Cardiovascular Medicine
lung transplantation
mass spectrometry
ex vivo lung perfusion
cytokine adsorption
proteomics
title Proteomic changes to immune and inflammatory processes underlie lung preservation using ex vivo cytokine adsorption
title_full Proteomic changes to immune and inflammatory processes underlie lung preservation using ex vivo cytokine adsorption
title_fullStr Proteomic changes to immune and inflammatory processes underlie lung preservation using ex vivo cytokine adsorption
title_full_unstemmed Proteomic changes to immune and inflammatory processes underlie lung preservation using ex vivo cytokine adsorption
title_short Proteomic changes to immune and inflammatory processes underlie lung preservation using ex vivo cytokine adsorption
title_sort proteomic changes to immune and inflammatory processes underlie lung preservation using ex vivo cytokine adsorption
topic lung transplantation
mass spectrometry
ex vivo lung perfusion
cytokine adsorption
proteomics
url https://www.frontiersin.org/articles/10.3389/fcvm.2023.1274444/full
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