Mesenchymal stromal cell derived membrane particles improve metabolic activity and functional performance during porcine kidney normothermic machine perfusion.

Abstract

Introduction Kidneys from donation after circulatory death (DCD) donors are increasingly used to alleviate organ shortage but highly vulnerable to ischemia-reperfusion injury, leading to poor graft outcomes. Normothermic machine perfusion (NMP) enables targeted intervention during donor kidney preservation. Membrane particles (MPs) derived from mesenchymal stromal cells (MSCs) have shown regenerative potential. We aimed to investigate MPs as a potential therapeutic strategy to improve metabolism and function in porcine DCD kidneys during NMP. Methods Six pairs of porcine kidneys underwent 4-hour NMP. Within each pair, one kidney received perfusate containing MPs derived from 1.0×107 MSCs, while the contralateral kidney served as a control. Hemodynamics, sodium reabsorption, oxygen consumption, and injury markers were monitored. Gene expression related to inflammation and metabolism were analyzed. Results MP administration did not affect renal blood flow or intrarenal resistance. Injury markers (AST, LDH, IL-6) were increased over time in both groups, without significant difference between MP-treated and control kidneys. In contrast, MP-treated kidneys showed significantly higher expression of metabolic genes (PDHB, ATP6V0D2, NDUFS8). Functionally, MP administration enhanced sodium reabsorption, urinary creatinine excretion, and oxygen utilization efficiency compared with controls. Conclusion MSC-derived MPs can be safely delivered to porcine kidneys and promote kidney functional performance and metabolic activity. These findings support MPs as a promising cell-free therapeutic strategy to improve the quality of kidneys during NMP.