Exosomal Small RNA From Donor Liver Preservation Solution Exhibits Molecular Signatures That Distinguish Organ Quality and Posttransplant Complications.

Background: Liver transplantation remains the optimal treatment for end-stage liver disease; however, the selection of suitable donors is often reliant on tissue biopsies that are invasive and reflective of only a portion of the liver. Prediction of posttransplant graft function or complications by molecular analyses of RNA profiles released by the liver during preservation would provide a more comprehensive and timely intervention to optimize recipient selection and survival. Methods: We collected exosomes from liver preservation fluid and identified differentially expressed small RNA profiles for different donor types and recipient outcomes. Our cohort consisted of donors after circulatory death or brain death, as well as living donors. Significant changes were determined by statistical analysis. Results: We demonstrate a successful method to collect exosomes from preservation fluid and isolate sufficient small RNA for sequencing analysis. MicroRNA (miRNA) profiles identified distinct groupings of living donors and donors after circulatory death types, with donor after circulatory death miRNA profiles providing a set of stress-induced biomarkers that project a greater propensity for poor function based on bioinformatic algorithms. Similarly, distinct miRNA profiles were expressed in different posttransplant complication groups. Conclusions: This method of exosomal collection for predictive miRNA signatures supports a promising technique for noninvasive sample collection to support patient-centered therapy after liver transplantation by identifying biomarkers for transplant outcomes.