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Excretion profile and detection of human adipose derived mesenchymal stem cells during and after isolated normothermic machine perfusion of ischemically damaged porcine kidneys

(2017) Eertman, T.B. (Tim)

Objectives: End-stage renal failure is a growing disease worldwide. The renal replacement therapy of choice is a kidney transplantation. Due to a shortage of suitable kidney grafts, the mean waiting time for a transplantation in the Netherlands is over 3.5 years. During this period morbidity and mortality increase. To reduce the shortage, more vulnerable grafts are transplanted. Machine perfusion (MP) of kidney grafts is used increasingly to improve graft quality. There is growing consensus on the beneficial immunomodulatoiry and anti-inflammatory features of mesenchymal stem cells (MSCs) in organ transplantation. In this study our aim was to gain more insights in the excretion products and detection of fluorescent-labeled MSCs during normothermic machine perfusion of an ischemically damaged porcine kidney. Methods: Two experimental perfusion groups consisted of a kidney with 0 (N=6) or 107 (N=5) MSCs added. In the third group solely 107 MSCs were added to the perfusion circuit in absence of a kidney (N=3). Cytokine release and graft function were measured and compared at multiple time points in every experimental group. Homing and migration of MSCs were analysed in tissue, perfusate and urine by flow-cytometry and fluorescence microscopy. Results: Not-significant trends were found in reduced urine output, lower injury marker AST and more suitable pH-regulation in kidneys exposed to MSCs. MSCs are found to be viable in glomeruli and perfusate during 6 hrs. of NMP. Degraded MCSs may have been found in collecting ducts and urine. Cytokines were detected in all 3 groups, indicating cross-reactivity and excretion through solely NMP-exposure occurred. Significant differences were found in IL-6 and IL-8 excretion. Conclusion: We succeeded in measuring functional parameters, cytokine analysis and detection of MSCs using fluorescence microscopy and flow-cytometry. Using Luminex, insights in excretion profile were obtained. Most findings were not significant, but provide sufficient evidence for conducting further research.





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