Cell-Based and Cell-Derived Therapies Delivered During Ex Vivo Machine Perfusion for Solid Organ Reconditioning Prior to Transplantation: A Systematic Review
- 1Imperial College London, South Kensington Campus, London SW7 2AZ, UK
- 2Department of Surgery and Cancer, Imperial College London, London SW7 5NH, UK
Abstract
Background/Objectives: Organ shortage is a major barrier to transplantation, leading to the emergence of marginal donor organs and extended criteria donor grafts and, alongside these, machine perfusion as a platform for reconditioning grafts to meet transplantation standards. Despite functioning as a reconditioning platform in its own right, machine perfusion also allows for the delivery of therapeutic agents directly to grafts prior to transplant. Cell-based and cell-derived therapies have been increasingly explored for delivery during this window, although evidence is fragmented across individual organ systems, and whether ex vivo benefit is confirmed post-transplant remains unclear. This systematic review aimed to synthesise the evidence from both perfusion-phase findings and post-transplant findings across solid organ machine perfusion, evaluating the concordance between the two. Methods: This review was prospectively registered on PROSPERO and conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidance. Included studies delivered cell-based or cell-derived therapies during ex vivo machine perfusion of a solid organ. The SYRCLE tool was used across all studies to assess risk of bias, and given substantial heterogeneity in cell type, protocol, and organ models, findings were synthesised narratively, with a sensitivity analysis restricted to the subset of studies incorporating a transplantation phase. Results: Thirty-one studies met inclusion criteria, spanning kidney (n = 10), liver (n = 11), lung (n = 9), and heart (n = 1). Mechanisms converged largely on immunomodulatory and metabolic pathways, most consistently reported across organs, alongside a less consistent but notable cross-organ parallel in regenerative progenitor activation between liver and kidney. Benefit was reported more consistently at the molecular and histological levels rather than the physiological level. Eight of the studies proceeded to transplantation, of which half showed a beneficial post-transplant result, and half showed mixed results. Conclusions: Cell-based and cell-derived therapies are best understood as adjuncts to the existing reconditioning capacity of machine perfusion. Molecular and mechanistic benefit was consistently reported; however, confirmation beyond the perfusion phase remained incomplete across organ systems. Mechanisms supported by direct interventional evidence represent priority candidates for further preclinical validation and independent replication.
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BibTeX
@article{alemi2026cellbased,
title = {{Cell-Based and Cell-Derived Therapies Delivered During Ex Vivo Machine Perfusion for Solid Organ Reconditioning Prior to Transplantation: A Systematic Review}},
author = {Mariam Alemi and Zara Edwards and Vassilios Papalois},
journal = {Journal of clinical medicine},
year = {2026},
month = oct,
doi = {10.3390/jcm15197698},
url = {https://europepmc.org/article/PMC/PMC13666490},
note = {CC BY},
}
RIS
TY - JOUR
TI - Cell-Based and Cell-Derived Therapies Delivered During Ex Vivo Machine Perfusion for Solid Organ Reconditioning Prior to Transplantation: A Systematic Review
AU - Mariam Alemi
AU - Zara Edwards
AU - Vassilios Papalois
PY - 2026
DA - 2026/10/01
JO - Journal of clinical medicine
DO - 10.3390/jcm15197698
UR - https://europepmc.org/article/PMC/PMC13666490
AB - Background/Objectives: Organ shortage is a major barrier to transplantation, leading to the emergence of marginal donor organs and extended criteria donor grafts and, alongside these, machine perfusion as a platform for reconditioning grafts to meet transplantation standards. Despite functioning as a reconditioning platform in its own right, machine perfusion also allows for the delivery of therapeutic agents directly to grafts prior to transplant. Cell-based and cell-derived therapies have been increasingly explored for delivery during this window, although evidence is fragmented across individual organ systems, and whether ex vivo benefit is confirmed post-transplant remains unclear. This systematic review aimed to synthesise the evidence from both perfusion-phase findings and post-transplant findings across solid organ machine perfusion, evaluating the concordance between the two. Methods: This review was prospectively registered on PROSPERO and conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidance. Included studies delivered cell-based or cell-derived therapies during ex vivo machine perfusion of a solid organ. The SYRCLE tool was used across all studies to assess risk of bias, and given substantial heterogeneity in cell type, protocol, and organ models, findings were synthesised narratively, with a sensitivity analysis restricted to the subset of studies incorporating a transplantation phase. Results: Thirty-one studies met inclusion criteria, spanning kidney (n = 10), liver (n = 11), lung (n = 9), and heart (n = 1). Mechanisms converged largely on immunomodulatory and metabolic pathways, most consistently reported across organs, alongside a less consistent but notable cross-organ parallel in regenerative progenitor activation between liver and kidney. Benefit was reported more consistently at the molecular and histological levels rather than the physiological level. Eight of the studies proceeded to transplantation, of which half showed a beneficial post-transplant result, and half showed mixed results. Conclusions: Cell-based and cell-derived therapies are best understood as adjuncts to the existing reconditioning capacity of machine perfusion. Molecular and mechanistic benefit was consistently reported; however, confirmation beyond the perfusion phase remained incomplete across organ systems. Mechanisms supported by direct interventional evidence represent priority candidates for further preclinical validation and independent replication.
SN - 2077-0383
ER -