Ex Vivo Administration of Mesenchymal Stromal Cells in Kidney Grafts Against Ischemia Reperfusion Injury - Effective Delivery Without Kidney Function Improvement Posttransplant

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  • Stine Lohmann
  • Marco Eijken
  • Ulla Møldrup
  • Bjarne K Møller
  • James Hunter, Department of Physiology, Anatomy & Genetics, University of Oxford, Oxford, United Kingdom; Department of Physics, University of Oxford, Oxford, United Kingdom; University of Oxford Centre for Clinical Magnetic Resonance Research, Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom.
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  • Cyril Moers, Department of Surgery, University Medical Center Groningen, Groningen, The Netherlands; Department of Pathology and Medical Biology, University Medical Center Groningen, Groningen, The Netherlands.
  • ,
  • Henri Leuvenink, Department of Surgery, University Medical Center Groningen, Groningen, The Netherlands; Department of Pathology and Medical Biology, University Medical Center Groningen, Groningen, The Netherlands.
  • ,
  • Rutger J Ploeg, Department of Physiology, Anatomy & Genetics, University of Oxford, Oxford, United Kingdom; Department of Physics, University of Oxford, Oxford, United Kingdom; University of Oxford Centre for Clinical Magnetic Resonance Research, Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom.
  • ,
  • Marian C Clahsen-van Groningen, Erasmus University Medical Center Cancer Institute, Department of Obstetrics and Gynaecology, Erasmus University Medical Center.
  • ,
  • Martin Hoogduijn, Erasmus University Medical Center Cancer Institute, Department of Obstetrics and Gynaecology, Erasmus University Medical Center.
  • ,
  • Carla C Baan, Erasmus University Medical Center Cancer Institute, Department of Obstetrics and Gynaecology, Erasmus University Medical Center.
  • ,
  • Anna Krarup Keller
  • Bente Jespersen

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.

Original languageEnglish
JournalTransplantation
ISSN0041-1337
DOIs
Publication statusE-pub ahead of print - 18 Sep 2020

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