Reconditioning of donor livers by Normothermic Machine Perfusion (NMP) is already increasing the numbers of transplantable organs from the extended criteria donors. The hepatoblastoma-derived cell line C3A is used as a surrogate for primary hepatocytes in ELAD® (Vital Therapies, Inc), an investigational human hepatic cell-based treatment comprised of C3A cell cartridges used to treat severe alcoholic hepatitis. C3A conditioned medium (C3ACM) has shown beneficial effects on isolated liver parenchymal cells, including reduction of inflammatory mediators, promotion of hepatocyte function and survival with improvement of bile acid metabolism. We investigated the impact of C3ACM on recovery of liver function during NMP of 13 discarded donor livers. Eight livers were perfused with C3ACM enhanced fluid, and 5 matched controls with blood-based perfusate only. Liver function was monitored up to 6 hours according to viability criteria established for clinical transplantation (lactate <2.5mmol/l). Sequential perfusate and tissue samples were taken for biochemical, histological and proteomic analysis. Nearly all (7 of 8, 88%) livers in the C3ACM group achieved viability. This compared with only 2 of 5 (40%) livers being viable in the control group. Histological assessment confirmed increased glycogen deposition in all livers meeting viability criteria, without revealing other changes. Transmission electron microscopy of C3ACM perfused livers showed improved ultrastructure over time. Comparative proteomic analysis yielded a panel of 54 proteins uniquely detectable in livers perfused with C3ACM consistent with the proposed beneficial effects reported in cell culture systems. This preliminary data suggests C3ACM might offer a novel therapeutic intervention capable of enhancing the reconditioning of extended criteria livers during NMP.

CITATION INFORMATION: Afford S., Wallace L., Laing R., Botteon Y., He D., Soundararajan S., Mirza D., Ashley R., Brotherton J., Mergental H., Reich D. Impact of ELAD C3A Cell Conditioned Medium Enhanced Perfusate Fluid on Functional Recovery of Extended Criteria Donor Livers during Normothermic Machine Perfusion Am J Transplant. 2017;17 (suppl 3).

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