Primary hepatocytes and their cultures in liver apoptosis research

Abstract

Apoptosis not only plays a key role in physiological demise of defunct hepatocytes, but is also associated with a plethora of acute and chronic liver diseases as well as with hepatotoxicity. The Europe PMC Funders Group Europe PMC Funders Author ManuscriptsEurope PMC Funders Author Manuscripts present paper focuses on the modelling of this mode of programmed cell death in primary hepatocyte cultures. Particular attention is paid to the activation of spontaneous apoptosis during the isolation of hepatocytes from the liver, its progressive manifestation upon the subsequent establishment of cell cultures and simultaneously to strategies to counteract this deleterious process. In addition, currently applied approaches to experimentally induce controlled apoptosis in this in vitro setting for mechanistic research purposes and thereby its detection using relevant biomarkers are reviewed.

The pseudokinase MLKL mediates programmed hepatocellular necrosis independently of RIPK3 during hepatitis

“…For the first time to our knowledge, we describe that IFN-γ signal transduction in hepatocytes, via activation of STAT1 and transactivation of the Mlkl promoter, rapidly increased the amount of MLKL transcripts and protein, which are low under steady-state conditions. PMHs display spontaneous cell death during long-term cell culture but show rather low sensitivity to necroptosis induction by TNF-α/zVAD/SMAC mimetic treatment (43,48). However, pretreatment of mice or cells with IFN-γ upregulated Mlkl in hepatocytes and increased their susceptibility toward cell death (Supplemental Figure 12).…”

Current progress in hepatic tissue regeneration by tissue engineering

“…The main obstacle is a confined hepatocyte proliferation and expansion rate in the 2D system. For instance, the hepatocyte proliferation rate is commonly decreased 3 to 5 days post-isolation and these cells are prone to de-differentiate and acquire fibroblast-like phenotype by modulation of hepatic-associated genes, leading to cell functionality removal and limitation of activity [148,149]. It has shown that the secretion of Alb, synthesis of urea, and expression of gene CYP3A4 are decreased in freshly isolated hepatocytes [150,151].…”

Characterization of hepatocyte-based in vitro systems for reliable toxicity testing

“…Upon dedifferentiation, hepatocytes adopt a fibroblast-like flattened phenotype. Hepatocytes either swell and become leaky, or shrink and produce apoptotic bodies when dying by necrosis or apoptosis, respectively (Fraczek et al 2013;Vinken et al 2014).…”