Ex Vivo Administration of Mesenchymal Stromal Cells in Kidney Grafts Against Ischemia Reperfusion Injury - Effective Delivery Without Kidney Function Improvement Posttransplant.
Lohmann S., Eijken M., Møldrup U., Møller BK., Hunter J., Moers C., Leuvenink H., Ploeg RJ., Clahsen-van Groningen MC., Hoogduijn M., Baan CC., Keller AK., Jespersen B.
BACKGROUND: Mesenchymal stromal cell (MSC) therapy may improve renal function after ischemia-reperfusion injury in transplantation. Ex vivo renal intraarterial administration is a targeted delivery method, avoiding the lung vasculature, a known barrier for cellular therapies. In a randomized and blinded study, we tested the feasibility and effectiveness of MSC therapy in a donation after circulatory death autotransplantation model to improve posttransplant kidney function, using an ex vivo MSC delivery method similar to the clinical standard procedure of pretransplant cold graft flush. METHODS: Kidneys exposed to 75 min of warm ischemia and 16 hrs of static cold storage were intraarterially infused ex vivo with 10 million male porcine MSCs (Tx-MSC, n=8) or vehicle (Tx-control, n=8). Afterwards, the kidneys were autotransplanted after contralateral nephrectomy. Biopsies an hour after reperfusion confirmed the presence of MSCs in the renal cortex. Animals were observed for 14 days. RESULTS: Postoperatively, peak p-creatinine was 1230 and 1274 µmol/L (Tx-controls vs Tx-MSC, p=0.69). During follow up, no significant differences over time were detected between groups regarding p-creatinine, p-NGAL, or u-NGAL/creatinine ratio. At day 14 measured glomerular filtration rates were 40 and 44 mL/min, p=0.66. Renal collagen content and fibrosis related mRNA expression were increased in both groups but without significant differences between the groups.In conclusion, we demonstrated intraarterial MSC infusion to transplant kidneys as a safe and effective method to deliver MSCs to the graft. However, we could not detect any positive effects of this cell treatment within 14 days of observation.