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

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 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.

Mesenchymal Stem Cell Protects Injured Renal Tubular Epithelial Cells by Regulating mTOR-Mediated Th17/Treg Axis

“…Currently, MSC has been extensively reported as a promising therapy for renal injury due to its renoprotection for injured RTEC (91)(92)(93). However, the therapeutic effect of MSC was greatly weakened in the light of the fact that a majority of MSC were stuck in the lungs after adoptive transfer, with a small part reaching to the spleen, liver, renal, and other organs (1,94).…”

Preconditioned Mesenchymal Stromal Cells to Improve Allotransplantation Outcome

“…In the transplantation field, the time between organ/tissue procurement and transplantation surgery provides a unique window to pretreat the transplant ex vivo, which can be regarded as an alternative way of local administration. In a kidney autotransplantation model, MSCs added during the normothermic machine perfusion stage can be retained within the kidney cortex for 14 days [ 79 ]. Pieróg et al infused the lung graft with hIL-10-BM-MSCs prior to implantation and found a significant improvement in the lung function on POD 5 [ 80 ].…”

Ex Vivo Mesenchymal Stem Cell Therapy to Regenerate Machine Perfused Organs

“…Neither negative effects on perfusion hemodynamics during NMP nor adverse effects on early transplantation outcome were observed. The study provided a proof of concept for ex vivo MSC application during NMP; however, no clear beneficial effect of MSC therapy during the short post-transplant follow-up period could be found [89].…”