Extracellular Vesicles Released During Normothermic Machine Perfusion Are Associated With Human Donor Kidney Characteristics
Transplantation, vol. 106, pp. 2360–2369
Abstract
BACKGROUND: Extracellular vesicles (EVs) are tissue-specific particles released by cells containing valuable diagnostic information in the form of various biomolecules. The characterization of EVs released by kidney grafts during normothermic machine perfusion (NMP) may present a promising avenue to assess graft status before transplantation. METHODS: We phenotyped and determined the concentrations of EVs in the perfusate of 8 discarded expanded-criteria donor human kidneys during 6 h of NMP. Perfusate samples were taken at 0/60/180/360 min and examined with nanoparticle tracking analysis and imaging flow cytometry (IFCM). Using IFCM, EVs were identified by their expression of common EV markers CD9, CD63, and CD81 (tetraspanins) in combination with either platelet endothelial cell adhesion molecule (CD31), pan-leukocyte protein (CD45), or carboxyfluorescein succiminidyl ester (CFSE) fluorescence. RESULTS: Nanoparticle tracking analysis measurements revealed the release of nanoparticles <400 nm into the perfusate during NMP. With IFCM, tetraspanin protein signatures of the released nanoparticles were characterized, and the majority (~75%) of CFSE+ EVs were found to be CD81+, whereas ~16% were CD9+ and ~8% CD63+. Correlation analysis of concentrations of identified EV subsets with crude donor characteristics and NMP viability characteristics revealed significant correlations with cold ischemia time, donor age, and renal flow. CONCLUSIONS: Our findings demonstrate that discarded expanded-criteria donor kidney grafts release distinct EV subsets during NMP. Because these subsets correlate with well-established indicators of transplant outcome, EVs might represent new potential candidates for assessment of kidney graft quality.
Authors 7
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Wouter W. Woud corresponding
Erasmus MC · Erasmus MC Transplant Institute
Affiliation as printed
Department of Internal Medicine, University Medical Center Rotterdam, Erasmus MC Transplant Institute, Rotterdam, The Netherlands
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Leiden University Medical Center
Affiliation as printed
Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands
Transplant Center, Leiden University Medical Center, Leiden, The Netherlands
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Leiden University Medical Center
Affiliation as printed
Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands
Transplant Center, Leiden University Medical Center, Leiden, The Netherlands
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Erasmus MC · Erasmus MC Transplant Institute
Affiliation as printed
Department of Internal Medicine, University Medical Center Rotterdam, Erasmus MC Transplant Institute, Rotterdam, The Netherlands
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Erasmus MC · Erasmus MC Transplant Institute
Affiliation as printed
Division of Hepato-Pancreato-Biliary and Transplant Surgery, Department of Surgery, Erasmus MC Transplant Institute, Erasmus MC, University Medical Center Rotterdam, Rotterdam,The Netherlands
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Erasmus MC · Erasmus MC Transplant Institute
Affiliation as printed
Department of Internal Medicine, University Medical Center Rotterdam, Erasmus MC Transplant Institute, Rotterdam, The Netherlands
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Erasmus MC · Erasmus MC Transplant Institute
Affiliation as printed
Department of Internal Medicine, University Medical Center Rotterdam, Erasmus MC Transplant Institute, Rotterdam, The Netherlands
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