The integration of regenerative medicine into dynamic organ preservation may mitigate ischemia-reperfusion injury in kidney transplantation. This systematic review and meta-analysis evaluated the therapeutic potential of stem cell-based interventions during machine perfusion. Following PRISMA guidelines, PubMed, Embase, and Scopus were searched for experimental studies using stem cells or extracellular vesicles (EVs) during hypothermic or normothermic machine perfusion in animal or discarded human kidneys. Outcomes included renal function, injury biomarkers, inflammation, and histology. Nine studies were included, seven in meta-analysis. Despite heterogeneity in models and protocols, several reported reductions in inflammatory cytokines (e.g., IL-6, IL-1β) and biomarkers (e.g., NGAL) following stem cell or EVs administration. However, meta-analysis showed no significant effects on creatinine clearance (Standardized Means (SMD): 0.00; 95% CI: –0.54 to 0.55), urine output (SMD: 0.54; 95% CI: –0.46 to 1.55), or NGAL (SMD: –1.68; 95% CI: –5.60 to 2.25). Histological protection varied, and stem cell retention was limited. Only one study assessed post-transplant function. While stem cell therapies during perfusion may have immunomodulatory and cytoprotective effects, consistent functional benefits were not observed. Further standardized studies, including transplant models and long-term outcomes, are needed to clarify therapeutic potential and optimize delivery strategies.

The authors thank Sandrina Vandenput, reference librarian of the CHU of Liege, for her help and advice in conducting the systematic literature search. This research was funded by the Fonds de la Recherche Scientifique FNRS (FRIA Fellowship), without involvement in study design, data collection, data-analysis, manuscript preparation and publication decisions. N.G. is supported by a Postdoctoral Clinical Master Specialist Fellowship by the Fund for Scientific Research (FRS/FNRS, 1R00424F). E.L. is supported by the ERC Consolidator Grant NEOGRAFT (CoG 101045467).

This research was funded by the Fonds de la Recherche Scientifique FNRS (FRIA Fellowship), without involvement in study design, data collection, data-analysis, manuscript preparation and publication decisions. N.G. is supported by a Postdoctoral Clinical Master Specialist Fellowship by the Fund for Scientific Research (FRS/FNRS, 1R00424F). E.L. is supported by the ERC Consolidator Grant NEOGRAFT (CoG 101045467).

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