Scimago Lab
powered by Scopus
call: +1.631.629.4327
Mon-Fri 10 am - 2 pm EST


Medical Science Monitor Basic Research


eISSN: 2329-0358

Get your full text copy in PDF

Alloresponses of Mixed Lymphocyte Hepatocyte Culture to Immunosuppressive Drugs as an In-Vitro Model of Hepatocyte Transplantation

Felix Oldhafer, Eva-Maria Wittauer, Christine S. Falk, Daphne E. DeTemple, Oliver Beetz, Kai Timrott, Moritz Kleine, Florian W.R. Vondran

(ReMediES, Department of General, Visceral and Transplant Surgery, Hannover Medical School, Hannover, Germany)

Ann Transplant 2019; 24:472-480

DOI: 10.12659/AOT.915982

BACKGROUND: Hepatocyte transplantation (HCTx) has the potential for the treatment of end-stage liver disease. However, failure of engraftment and the long-term acceptance of cellular allografts remain significant challenges for its clinical application. The aim of this study was to investigate the efficacy of the immunosuppressive agents, Cyclosporine, Everolimus, and Belatacept to suppress the alloresponse of primary human hepatocytes in a mixed lymphocyte-hepatocyte culture (MLHC) and their potential hepatotoxicity in vitro.
MATERIAL AND METHODS: Primary human hepatocytes were co-cultured with allogeneic peripheral blood mononuclear cells (PBMCs) in an MLHC. Proliferative alloresponses were determined by flow cytometry, and cytokine secretion was measured using Luminex-based multiplex technology. Using an MLHC, the alloresponses of primary human hepatocytes were compared in the presence and absence of Cyclosporine, Everolimus, and Belatacept. Cultured primary human hepatocytes were assessed for the production of albumin, urea, aspartate transaminase (AST) and DNA content. Metabolic activity was determined with the MTT assay.
RESULTS: Immune responses induced by primary human hepatocytes were effectively suppressed by Cyclosporine, Everolimus, and Belatacept. Everolimus significantly reduced the metabolic activity of primary human hepatocytes in vitro, suggesting impairment of cell viability. However, further functional analysis showed no significant differences between treated and untreated controls.
CONCLUSIONS: Cyclosporine, Everolimus, and Belatacept suppressed the alloresponse of primary human hepatocytes in an MLHC without significant cytotoxicity or functional cell impairment.

This paper has been published under Creative Common Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) allowing to download articles and share them with others as long as they credit the authors and the publisher, but without permission to change them in any way or use them commercially.
I agree