Mesenchymal Stromal Cells as Anti-Inflammatory and Regenerative Mediators for Donor Kidneys During Normothermic

Jesus Maria Sierra-Parraga1, Marco Eijken2, James Hunter3

  • 11 Department of Internal Medicine, Nephrology and Transplantation, Erasmus MC, University Medical Center , Rotterdam, the Netherlands .

Insights

Normothermic machine perfusion (NMP) combined with mesenchymal stromal cells (MSC) shows promise for improving kidney transplant outcomes. This approach aims to reduce injury and enhance repair in donor kidneys, expanding the potential for life-saving transplants.

Area of Science:

  • Transplantation immunology
  • Regenerative medicine
  • Organ preservation

Background:

  • Increasing demand for kidney transplants necessitates utilizing organs from expanded criteria donors (ECD) and donation after circulatory death (DCD).
  • Ischemia/reperfusion injury significantly impacts graft survival, especially in deceased donor kidneys.
  • Hypothermic machine perfusion (HMP) has improved outcomes for marginal organs compared to static cold storage.

Purpose of the Study:

  • To evaluate the therapeutic potential of combining normothermic machine perfusion (NMP) with mesenchymal stromal cells (MSC) for kidney preservation.
  • To investigate the mechanisms of injury and repair in donor kidneys treated with NMP and MSC ex vivo.
  • To lay the groundwork for future human clinical trials of this novel transplantation strategy.

Main Methods:

  • Utilizing a porcine kidney autotransplantation model.
  • Administering mesenchymal stromal cells (MSC) during normothermic machine perfusion (NMP).
  • Assessing the effects of NMP-MSC treatment on kidney injury and repair mechanisms.

Main Results:

  • The study is designed to assess therapeutic effects and mechanisms, with results pending further investigation.
  • Preliminary data suggests NMP allows for organ assessment and potential therapeutic interventions.
  • MSC demonstrate regenerative properties through paracrine effectors.

Conclusions:

  • The combination of NMP and MSC represents a promising strategy to mitigate ischemia/reperfusion injury and enhance kidney graft quality.
  • This approach could expand the donor pool and improve outcomes for patients awaiting kidney transplantation.
  • The MePEP consortium's research is crucial for advancing ex vivo organ perfusion therapies towards clinical application.