Data from: Activation of autophagy during normothermic machine perfusion of discarded livers is associated with improved hepatocellular function
Ohman, Anders et al. (2021), Data from: Activation of autophagy during normothermic machine perfusion of discarded livers is associated with improved hepatocellular function, Dryad, Dataset, https://doi.org/10.5061/dryad.f7m0cfxx0
Liver transplantation is hampered by a severe shortage of donor organs. Normothermic machine perfusion (NMP) of donor livers allows dynamic preservation in addition to viability assessment prior to transplantation. Little is known about the injury and repair mechanisms induced during NMP. To investigate these mechanisms, we examined gene and protein expression changes in a cohort of discarded human livers, stratified by hepatocellular function, during NMP. Six human livers acquired through donation after circulatory death (DCD) underwent 12 hours of NMP. Of the 6, 3 met predefined criteria for adequate hepatocellular function. We applied transcriptomic profiling and protein analysis to evaluate temporal changes in gene expression during NMP between functional and nonfunctional livers. Principal component analysis segregated the two groups and distinguished the various perfusion time points. Transcriptomic analysis of biopsies from functional livers indicated robust activation of innate immunity after 3 hours of NMP followed by enrichment of pro-repair and pro-survival mechanisms. Nonfunctional livers demonstrated delayed and persistent enrichment of markers of innate immunity. Functional livers demonstrated effective induction of autophagy, a cellular repair and homeostasis pathway, in contrast to nonfunctional livers. In conclusion, NMP of discarded DCD human livers results in innate immune-mediated injury, while also activating autophagy, a presumed mechanism for support of cellular repair. More pronounced activation of autophagy was seen in livers that demonstrated adequate hepatocellular function.
National Institute of Environmental Health Sciences, Award: T32ES007272
Massachusetts General Hospital Executive Committee on Research
National Institutes of Diabetes and Digestive and Kidney Diseases, Award: R01DK096075, R01DK107875, R01DK114506
National Science Foundation, Award: EEC 1941543, ATP-Bio
Rhode Island Hospital/Brown University Department of Pediatrics