TY - JOUR
T1 - Ex Vivo Administration of Mesenchymal Stromal Cells in Kidney Grafts Against Ischemia-reperfusion Injury—Effective Delivery Without Kidney Function Improvement Posttransplant
AU - Lohmann, Stine
AU - Eijken, Marco
AU - Møldrup, Ulla
AU - Møller, Bjarne K
AU - Hunter, James
AU - Moers, Cyril
AU - Leuvenink, Henri
AU - Ploeg, Rutger J
AU - Clahsen-van Groningen, Marian C
AU - Hoogduijn, Martin
AU - Baan, Carla C
AU - Keller, Anna Krarup
AU - Jespersen, Bente
N1 - Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.
PY - 2021/3
Y1 - 2021/3
N2 - 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.
AB - 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.
U2 - 10.1097/TP.0000000000003429
DO - 10.1097/TP.0000000000003429
M3 - Journal article
C2 - 32956281
SN - 0041-1337
VL - 105
SP - 517
EP - 528
JO - Transplantation
JF - Transplantation
IS - 3
ER -