From Preservation to Regeneration: Stem Cell-Derived Therapies in Machine-Perfused Kidney Transplants - A Systematic Review and Meta-Analysis.

Abstract

Introduction: Ischemia-reperfusion injury remains a critical determinant of graft outcomes in kidney transplantation, contributing to delayed graft function and reduced long-term survival. Machine perfusion has emerged as a dynamic preservation strategy offering a therapeutic window to condition organs prior to implantation. The integration of stem cells and extracellular vesicles (EVs), known for their immunomodulatory and cytoprotective properties, into perfusion protocols represents a novel and potentially synergistic approach. However, the evidence base remains limited and heterogeneous.

Methods: 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 EVs during hypothermic or normothermic machine perfusion in animal or discarded human kidneys. Outcomes included renal function, injury biomarkers, inflammation, and histology.

Results: Nine studies were included, seven in meta-analysis. Several reported reductions in inflammatory cytokines (IL-6, IL-1β) and biomarkers (NGAL) following stem cell or EV administration. However, meta-analysis showed no significant effects on creatinine clearance (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). Stem cell retention was limited, mechanisms of action remain incompletely understood, and only one study assessed post-transplant function.

Conclusion: Despite potential immunomodulatory and cytoprotective effects, consistent functional benefits were not demonstrated. Standardized studies incorporating transplant models and long-term outcomes are needed to clarify therapeutic potential and optimize delivery strategies.