Novel delivery of cellular therapy to reduce ischaemia reperfusion injury in kidney transplantation

Ex-vivo normothermic machine perfusion (NMP) of donor kidneys prior to transplantation provides a platform for direct delivery of cellular therapeutics to optimise organ quality prior to transplantation. Multipotent Adult Progenitor Cells (MAPC® ) possess potent immunomodulatory properties which could minimise ischaemia reperfusion injury. We investigated the potential capability of MAPC cells in kidney NMP. Pairs (5) of human kidneys, from the same donor, were simultaneously perfused for 7-hours. Kidneys were randomly allocated to receive MAPC treatment or control. Serial samples of perfusate, urine and tissue biopsies were taken for comparison. MAPC-treated kidneys demonstrated improved urine-output (p=0.009), decreased expression of injury biomarker NGAL (p=0.012), improved microvascular perfusion on contrast enhanced ultrasound (cortex p=0.019, medulla p=0.001), downregulation of IL-1β (p=0.050) and upregulation of IL-10 (p<0.047) and Indolamine-2, 3-dioxygenase (p=0.050). A chemotaxis model demonstrated decreased neutrophil recruitment when stimulated with perfusate from MAPC-treated kidneys (p<0.001). Immunofluorescence revealed pre-labelled MAPC cells in the perivascular space of kidneys during NMP. We report the first successful delivery of cellular therapy to a human kidney during NMP. Kidneys treated with MAPC cells demonstrate improvement in clinically relevant parameters and injury biomarkers. This novel method of cell therapy delivery provides an exciting opportunity to recondition organs prior to transplantation.