Contributions, bias, and research gaps in large animal ex vivo lung perfusion models: A systematic review

Background: A major challenge in lung transplantation is the shortage of viable donor lungs. Ex vivo lung perfusion (EVLP) has emerged as an effective assessment and conditioning tool to expand the donor lung pool. This systematic review sought to establish the contribution of large animal models to...

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Main Authors: Shane Fisher, James O’Connor, Karen Redmond
Format: Article
Language:English
Published: Elsevier 2025-11-01
Series:JHLT Open
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Online Access:http://www.sciencedirect.com/science/article/pii/S295013342500151X
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author Shane Fisher
James O’Connor
Karen Redmond
author_facet Shane Fisher
James O’Connor
Karen Redmond
author_sort Shane Fisher
collection DOAJ
description Background: A major challenge in lung transplantation is the shortage of viable donor lungs. Ex vivo lung perfusion (EVLP) has emerged as an effective assessment and conditioning tool to expand the donor lung pool. This systematic review sought to establish the contribution of large animal models to EVLP development and application, particularly focusing on assessing the risk of bias and the certainty of evidence. Methods: A strategic literature search was conducted using a predefined pro forma. Relevant data were extracted, and thematic analysis was applied for qualitative synthesis of key measures. Methodological quality and bias risk were assessed using systematic review centre for laboratory animal experimentation’s risk of bias tool, and certainty of evidence was evaluated using the grading of recommendations assessment, development and evaluation Framework. Results: A total of 32 studies met the inclusion criteria, using porcine, ovine, rabbit, and canine models. Key themes included EVLP’s role in donor lung assessment and preservation, marginal donor lung repair, and as an experimental translational platform. All studies were assessed with the systematic review centre for laboratory animal experimentation tool and had a high or unclear risk of bias. Twenty-eight (87.5%) showed low certainty of evidence, 2 (6.25%) very low, and 2 (6.25%) moderate, raising concerns about overall evidence strength. Conclusions: Large animal EVLP models have significantly advanced donor lung preservation, reconditioning, and therapeutic intervention. However, methodological bias remains a concern due to inconsistent adherence to reporting and procedural standards. Greater conformity to standardized protocols is pivotal to improve the reliability, reproducibility, and translational value of future EVLP research.
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spelling doaj-art-db4e3ca2f1f24c41b93aed6aa28399dc2025-08-20T03:38:22ZengElsevierJHLT Open2950-13342025-11-011010035610.1016/j.jhlto.2025.100356Contributions, bias, and research gaps in large animal ex vivo lung perfusion models: A systematic reviewShane Fisher0James O’Connor1Karen Redmond2Department of Medicine, St James's Hospital Dublin, Dublin, Ireland; Corresponding author: Shane Fisher, Department of Medicine, St James’s Hospital, Dublin, Ireland.Royal College of Surgeons Ireland, Dublin, Ireland; Mater Misericordiae University Hospital Dublin, Dublin, IrelandRoyal College of Surgeons Ireland, Dublin, Ireland; Mater Misericordiae University Hospital Dublin, Dublin, Ireland; University College Dublin, Dublin, IrelandBackground: A major challenge in lung transplantation is the shortage of viable donor lungs. Ex vivo lung perfusion (EVLP) has emerged as an effective assessment and conditioning tool to expand the donor lung pool. This systematic review sought to establish the contribution of large animal models to EVLP development and application, particularly focusing on assessing the risk of bias and the certainty of evidence. Methods: A strategic literature search was conducted using a predefined pro forma. Relevant data were extracted, and thematic analysis was applied for qualitative synthesis of key measures. Methodological quality and bias risk were assessed using systematic review centre for laboratory animal experimentation’s risk of bias tool, and certainty of evidence was evaluated using the grading of recommendations assessment, development and evaluation Framework. Results: A total of 32 studies met the inclusion criteria, using porcine, ovine, rabbit, and canine models. Key themes included EVLP’s role in donor lung assessment and preservation, marginal donor lung repair, and as an experimental translational platform. All studies were assessed with the systematic review centre for laboratory animal experimentation tool and had a high or unclear risk of bias. Twenty-eight (87.5%) showed low certainty of evidence, 2 (6.25%) very low, and 2 (6.25%) moderate, raising concerns about overall evidence strength. Conclusions: Large animal EVLP models have significantly advanced donor lung preservation, reconditioning, and therapeutic intervention. However, methodological bias remains a concern due to inconsistent adherence to reporting and procedural standards. Greater conformity to standardized protocols is pivotal to improve the reliability, reproducibility, and translational value of future EVLP research.http://www.sciencedirect.com/science/article/pii/S295013342500151Xlung transplantationex vivo lung perfusionlarge animal modelpreclinical modelstranslational research
spellingShingle Shane Fisher
James O’Connor
Karen Redmond
Contributions, bias, and research gaps in large animal ex vivo lung perfusion models: A systematic review
JHLT Open
lung transplantation
ex vivo lung perfusion
large animal model
preclinical models
translational research
title Contributions, bias, and research gaps in large animal ex vivo lung perfusion models: A systematic review
title_full Contributions, bias, and research gaps in large animal ex vivo lung perfusion models: A systematic review
title_fullStr Contributions, bias, and research gaps in large animal ex vivo lung perfusion models: A systematic review
title_full_unstemmed Contributions, bias, and research gaps in large animal ex vivo lung perfusion models: A systematic review
title_short Contributions, bias, and research gaps in large animal ex vivo lung perfusion models: A systematic review
title_sort contributions bias and research gaps in large animal ex vivo lung perfusion models a systematic review
topic lung transplantation
ex vivo lung perfusion
large animal model
preclinical models
translational research
url http://www.sciencedirect.com/science/article/pii/S295013342500151X
work_keys_str_mv AT shanefisher contributionsbiasandresearchgapsinlargeanimalexvivolungperfusionmodelsasystematicreview
AT jamesoconnor contributionsbiasandresearchgapsinlargeanimalexvivolungperfusionmodelsasystematicreview
AT karenredmond contributionsbiasandresearchgapsinlargeanimalexvivolungperfusionmodelsasystematicreview