Infusing Mesenchymal Stromal Cells into Porcine Kidneys during Normothermic Machine Perfusion: Intact MSCs Can Be Traced and Localised to Glomeruli

Merel Pool*, Tim Eertman, Jesus Sierra Parraga, Nils 't Hart, Marieke Roemeling-van Rhijn, Marco Eijken, Bente Jespersen, Marlies Reinders, Martin Hoogduijn, Rutger Ploeg, Henri Leuvenink, Cyril Moers

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

15 Citations (Scopus)
136 Downloads (Pure)

Abstract

Normothermic machine perfusion (NMP) of kidneys offers the opportunity to perform active interventions, such as the addition of mesenchymal stromal cells (MSCs), to an isolated organ prior to transplantation. The purpose of this study was to determine whether administering MSCs to kidneys during NMP is feasible, what the effect of NMP is on MSCs and whether intact MSCs are retained in the kidney and to which structures they home. Viable porcine kidneys were obtained from a slaughterhouse. Kidneys were machine perfused during 7 h at 37 C. After 1 h of perfusion either 0, 105, 106 or 107 human adipose tissue derived MSCs were added. Additional ex vivo perfusions were conducted with fluorescent pre-labelled bone-marrow derived MSCs to assess localisation and survival of MSCs during NMP. After NMP, intact MSCs were detected by immunohistochemistry in the lumen of glomerular capillaries, but only in the 107 MSC group. The experiments with fluorescent pre-labelled MSCs showed that only a minority of glomeruli were positive for infused MSCs and most of these glomeruli contained multiple MSCs. Flow cytometry showed that the number of infused MSCs in the perfusion circuit steeply declined during NMP to approximately 10%. In conclusion, the number of circulating MSCs in the perfusate decreases rapidly in time and after NMP only a small portion of the MSCs are intact and these appear to be clustered in a minority of glomeruli.

Original languageEnglish
Article number3607
Number of pages15
JournalInternational Journal of Molecular Sciences
Volume20
Issue number14
DOIs
Publication statusPublished - 23-Jul-2019

Keywords

  • kidney transplantation
  • porcine
  • organ preservation
  • mesenchymal stromal cells
  • normothermic machine perfusion
  • STEM-CELLS
  • RENAL-TRANSPLANTATION
  • CARDIAC DEATH
  • PRESERVATION
  • DONATION

Cite this