526.13 - MicroRNA Drivers for Regenerative Capacity in Liver Transplantation

Ankita Srivastava (Thomas Jefferson University), Benjamin Barnhart (Thomas Jefferson University), Jan Hoek (Thomas Jefferson University), Rajanikanth Vadigepalli (Thomas Jefferson University)

Liver diseases, including alcoholic liver disease, nonalcoholic fatty liver disease, hepatitis, hepatocellular carcinoma, and other end-stage chronic liver disease complications, often require liver transplantation. There is an unmet demand for liver transplantation due to a limited availability of deceased-donor livers with adequate regenerative capacity. Current efforts to address this need involve treatments to improve transplant outcomes and utilize livers with diminished regenerative potential. Hence it is imperative to characterize the regenerative potential of donor livers for maximizing the utilization of available organs. We aim to identify microRNAs that can serve as potential markers of regeneration potential of the donor livers. For this study, flash-frozen wedge-biopsy samples were received from the Thomas Jefferson surgical team collected under the approved consent to research authorization obtained by the Gift of Life Donor Program. We compared samples of donor livers selected for transplant to those deemed non-transplantable by the surgical staff. We profiled 798 microRNAs using the NanoString miRNA nCounter assay. The data normalization was performed using tools in the R platform. ANOVA test revealed a cohort of 15 microRNAs upregulated in the rejected livers compared to the livers accepted for transplantation. Further evaluation of microRNA targets will provide insights into mechanisms driving regenerative capacity of donor livers, which can aid the development of therapeutic interventions using microRNAs in liver transplantation.

Funding: National Institute of Alcoholism and Alcohol Abuse: R01 AA018873; National Institute of Biomedical Imaging and Bioengineering: U01 EB023224.