Functional and morphological comparison of three primary liver cell types cultured in the AMC bioartificial liver

Abstract

The selection of a cell type for bioartificial liver (BAL) systems for the treatment of patients with acute liver failure is in part determined by issues concerning patient safety and cell availability. Consequently, mature porcine hepatocytes (MPHs) have been widely applied in BAL systems. The success of clinical BAL application systems is, however, largely dependent on the functionality and stability of hepatocytes. Therefore, we compared herein the general metabolic and functional activities of MPHs with mature human hepatocytes (MHHs) in the Academic Medical Center (AMC)-BAL during a 7-day culture period. We also tested fetal human hepatocytes (FHHs), since their proliferation capacity is higher than MHHs and their function is increased compared to human liver cell lines. The results showed large differences between the 3 cell types. MHHs eliminated 2-fold more ammonia and produced 3-fold more urea than MPHs, whereas FHHs produced ammonia. Lidocaine elimination of FHHs was 3.5-fold higher than MPHs and 6.6-fold higher than of MHHs. Albumin production was not different between the 3 cell types. MPHs and FHHs became increasingly glycolytic, whereas MHHs remained metabolically stable during the whole culture period. MHHs and MPHs formed tissue-like structures inside the AMC-BAL. In conclusion, we propose that FHHs can be considered as a suitable cell type for pharmacological studies inside a bioreactor. However, we conclude that MHHs are the preferred cell source for loading a BAL device for clinical use, because of their high ammonia eliminating capacity and metabolic stability. MPHs should be considered as the best alternative cell source for BAL application, although their phenotypic instability urges application within 1 or 2 days after loading. Liver Transpl 13:589-598, 2007.

Heterotypic interactions in the preservation of morphology and functionality of porcine hepatocytes by bone marrow mesenchymal stem cells in vitro

“…Due to physiological similarities with human hepatocytes as well as ready availability, porcine hepatocytes have been serving as the most ideal cell source to be used in both pre-clinical and clinical liver support (Demetriou et al, 2004;Poyck et al, 2007). Recent attempts to improve hepatocyte morphology and function in vitro include the use of various medium supplementation, extracellular matrix (ECM) components, and co-cultivation of hepatocytes with liver-derived or non-liver derived mesenchymal cells (Thomas et al, 2005;Zinchenko and Coger, 2005;Price et al, 2006;Seo et al, 2006a,b;Nishikawa et al, 2008).…”

Problems and prospects of creation of extracorporal systems for support of functional livers status

“…Сравнение метаболизма ПГЧ, фетальных гепатоцитов человека (ФГЧ) и гепатоцитов свиней в аппарате "ЭБИП" показало, что способность ПГЧ к удалению аммиака и синтезу мочевины в 2 и 3 раза соответственно выше по сравнению с гепатоцитами свиней [34]. В то же время, метаболизм лидокаина у ФГЧ был в 3,5 раза выше, чем у гепатоцитов свиней.…”

Evaluation of a new immortalized human fetal liver cell line (cBAL111) for application in bioartificial liver

“…Immunostaining was performed on complete transverse 8 lm sections of 4% paraformaldehyde-fixed and paraplast embedded bioreactors, as described [10,11].…”