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

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

DOI

  • Stine Lohmann
  • Marco Eijken
  • Ulla Møldrup
  • Bjarne K Møller
  • James Hunter, University of Oxford
  • ,
  • 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, University of Oxford
  • ,
  • 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.

OriginalsprogEngelsk
TidsskriftTransplantation
Vol/bind105
Nummer3
Sider (fra-til)517-528
Antal sider12
ISSN0041-1337
DOI
StatusUdgivet - mar. 2021

Se relationer på Aarhus Universitet Citationsformater

ID: 197155176