Mesenchymal stromal cell treatment of donor kidneys during ex-vivo normothermic machine perfusion: A porcine renal autotransplantation study

Stine Lohmann*, Merel B. F. Pool, K M Rozenberg, Anna Krarup Keller, C Moers, Ulla Møldrup, Bjarne K. Møller, Stina Julia Maria Lignell, Søren Krag, Jesus M. Sierra-Parraga, M L Lo Faro, J Hunter, M J Hoogduijn, C C Baan, Hgd Leuvenink, R J Ploeg, Marco Eijken, Bente Jespersen

*Corresponding author for this work

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

37 Citations (Scopus)

Abstract

Normothermic machine perfusion (NMP) of injured kidneys offers the opportunity for interventions to metabolically active organs prior to transplantation. Mesenchymal stromal cells (MSCs) can exert regenerative and anti-inflammatory effects in ischaemia-reperfusion injury. The aims of this study were to evaluate the safety and feasibility of MSC treatment of kidneys during NMP using a porcine auto-transplantation model, and examine potential MSC treatment-associated kidney improvements up to 14 days post transplantation. After 75 minutes of kidney warm ischaemia, four experimental groups of n=7 underwent 14 hours of oxygenated hypothermic machine perfusion. In three groups this was followed by 240 minutes of NMP with infusion of vehicle, ten million porcine or ten million human adipose derived MSCs. All kidneys were auto-transplanted after contralateral nephrectomy. MSC treatment did not affect perfusion haemodynamics during NMP or cause adverse effects at reperfusion, with 100% animal survival. MSCs did not affect plasma creatinine, glomerular filtration rate, neutrophil gelatinase-associated lipocalin concentrations or kidney damage assessed by histology during the 14 days, and MSCs retention was demonstrated in renal cortex. Infusing MSCs during ex vivo NMP of porcine kidneys was safe and feasible. Within the short post- transplant.

Original languageEnglish
JournalAmerican Journal of Transplantation
Volume21
Issue7
Pages (from-to)2348-2359
Number of pages12
ISSN1600-6135
DOIs
Publication statusPublished - Jul 2021

Keywords

  • basic (laboratory) research/science
  • donors and donation: donation after circulatory death (DCD)
  • ischemia reperfusion injury (IRI)
  • kidney transplantation/nephrology
  • organ perfusion and preservation
  • organ procurement and allocation
  • regenerative medicine
  • stem cells

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