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 ischemia-reperfusion injury. The aims of this study were to evaluate the safety and feasibility of MSC treatment of kidneys during NMP using a porcine autotransplantation model, and examine potential MSC treatment-associated kidney improvements up to 14 days posttransplant. After 75 min of kidney warm ischemia, four experimental groups of n = 7 underwent 14 h of oxygenated hypothermic machine perfusion. In three groups this was followed by 240 min of NMP with infusion of vehicle, 10 million porcine, or 10 million human adipose-derived MSCs. All kidneys were autotransplanted after contralateral nephrectomy. MSC treatment did not affect perfusion hemodynamics 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 posttransplant follow-up period, no beneficial effects of ex vivo MSC therapy could be demonstrated.
Bibliographical noteFunding Information:
The authors thank the following people for assistance: laboratory technician Karin Christensen, Maria Arge, and Birgitte Sahl, Department of Renal Medicine, Aahurs University Hospital as well as Lene Elsebeth Nielsen from Department of Nuclear Medicine & PET-Centre, Aarhus University Hospital for 99Tc-diethylenetriamine pentaacetic acid analysis. They thank their expert statistician Associated Professor Bo Martin Bibby and Aparna Udupi, Department of Public Health ? Department of Biostatistics, Aarhus University for statistical consulting and assistance. This work was supported by the Lundbeck Foundation, grant number R198-2015-184 and by the Dutch Kidney Foundation, grant number 14OKG01. The funding sources had no role in the study design; in the collection, analysis, or interpretation of data; in the writing of the report or the decision to submit the article for publication.
© 2021 The American Society of Transplantation and the American Society of Transplant Surgeons