Infusion of human mesenchymal stromal cells during normothermic machine perfusion of discarded human kidneys: a randomized, blinded, paired, preclinical study

Abstract Normothermic machine perfusion (NMP) enables pre-transplant organ assessment and therapeutic delivery. Mesenchymal stromal cells (MSCs) may limit ischemia-reperfusion injury, but their delivery to human kidneys during NMP has not been tested in a controlled setting. Seven pairs of discarded human kidneys underwent 6-hour NMP. In each pair, one kidney received intra-arterial injection of 10 million clinical-grade bone marrow-derived human MSCs 45 minutes after perfusion onset; the paired kidney received placebo. Primary outcomes were feasibility and safety; secondary outcomes included functional, injury, cytokine, and histological parameters, assessed blindly. Renal blood flow and intrarenal resistance improved significantly over time (p < 0.0001; p = 0.04), with no significant between-group difference, though MSC-treated kidneys trended toward higher flow and lower resistance early in perfusion. Urine output and creatinine clearance increased over time in both groups (p = 0.009; p = 0.01) and were numerically higher with MSCs, without reaching significance (p = 0.61; p = 0.40). NGAL was numerically lower in MSC-treated kidneys later in perfusion; cytokine and histological profiles were comparable. This first blinded, randomized, paired, controlled study shows clinical-grade hMSC delivery during human kidney NMP is safe and translatable. Consistent functional trends suggest a biological signal, supporting an adequately powered confirmatory trial using this paired discarded kidney model.