Mesenchymal Stromal Cell Treatment of Kidneys During Normothermic Machine Perfusion is Safe and Feasible with Effective Traceability after Transplantation
1Nuffield Department of Surgical Sciences, University of Oxford, Oxford, United Kingdom, 2Department of Clinical Medicine, Aarhus University, Aarhus, Denmark, 3Department of Surgery, University Medical Center Groningen, Groningen, Netherlands, 4Department of Renal Medicine, Aarhus University, Aarhus, Denmark, 5Department of Urology, Aarhus University, Aarhus, Denmark, 6Department of Clinical Immunology, Aarhus University, Aarhus, Denmark, 7Department of Internal Medicine, Nephrology and Transplantation, Erasmus MC, University Medical Center, Rotterdam, Netherlands
Meeting: 2020 American Transplant Congress
Abstract number: B-349
Keywords: Kidney, Machine preservation, Renal ischemia, Stem cells
Session Information
Session Name: Poster Session B: Ischemia Reperfusion & Organ Rehabilitation
Session Type: Poster Session
Date: Saturday, May 30, 2020
Session Time: 3:15pm-4:00pm
Presentation Time: 3:30pm-4:00pm
Location: Virtual
*Purpose: Marginal kidneys are increasingly being accepted to decrease waiting time for a transplant. Normothermic machine perfusion (NMP) is a technique that allows delivery of therapies that may help condition or repair the organ prior to transplantation. Mesenchymal stromal cells (MSC) may be able to ameliorate ischaemia reperfusion injury as they possess potent anti-inflammatory and regenerative properties. We investigated the safety and effect of MSC administered during ex vivo NMP prior to transplantation in a pig auto-transplant model of donation after circulatory death.
*Methods: Porcine kidneys were subjected to 75 min warm ischaemia, retrieved and preserved for 14h by oxygenated HMP (oxHMP) followed by 4h NMP prior to auto-transplantation. Kidneys were randomised to four groups (n=7 per group): oxHMP alone; oxHMP plus NMP and vehicle (NMP); oxHMP plus NMP with 10 million pig MSC (NMP+pMSC); or oxHMP plus NMP with 10 million human MSC (NMP+hMSC). The pig was re-anaesthetised, the contralateral kidney was removed and the treated kidney was auto-transplanted and the animals were recovered for 14 days.
*Results: Renal blood flow during NMP was no different between the groups (p=0.0685). Post-transplant plasma creatinine increased in all groups but there were no significant differences between the groups (p=0.517). Plasma kidney injury biomarker NGAL was significantly higher in the NMP+pMSC group compared to the NMP (p=0.003) and NMP+hMSC (p=0.017) groups at day 14. On day 14, mGFR significantly improved in the NMP group compared to the control (55 ± 3 vs 42 ± 12 ml/min, p=0.025). No differences in GFR were observed on day 14 in the other groups (NMP+pMSC, p=0.090 and NMP+hMSC, p=0.090). MSC were detectable in biopsies of MSC treated kidney after NMP and post-transplantation.
*Conclusions: Conclusion: NMP alone improved renal graft function compared to oxHMP of DCD kidneys post-transplant. The method of MSC administration during NMP proved to be safe, however in this model MSC treatment did not improve renal function. Nevertheless viable MSC remained detectable in the transplanted kidney at postoperative day 14 which may have an effect on longer term outcomes.
To cite this abstract in AMA style:
Rozenberg K, Lohmann S, Pool M, Eijken M, Møldrup U, Møller B, Sierra-Parraga J, Hoogduijn M, Faro LLo, Moers C, Hunter J, Keller A, Leuvenink H, Baan C, Ploeg R, Jespersen B. Mesenchymal Stromal Cell Treatment of Kidneys During Normothermic Machine Perfusion is Safe and Feasible with Effective Traceability after Transplantation [abstract]. Am J Transplant. 2020; 20 (suppl 3). https://atcmeetingabstracts.com/abstract/mesenchymal-stromal-cell-treatment-of-kidneys-during-normothermic-machine-perfusion-is-safe-and-feasible-with-effective-traceability-after-transplantation/. Accessed November 22, 2024.« Back to 2020 American Transplant Congress