Primary hepatocyte cultures for liver disease modeling

Vinken, Mathieu

doi:10.1016/j.cotox.2020.08.003

Cited by 7 publications

(6 citation statements)

References 44 publications

(40 reference statements)

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“…Next to the isolated mitochondria, hepatocyte culture systems are yet another highly valuable tool to study mitochondrial toxicity and dysfunction. Despite being used successfully for mitochondrial dysfunction studies and representing the gold standard and most relevant model from the clinical translational point of view, primary human hepatocytes do have some limitations [ 193 , 194 , 195 ]. These include inter-individual variability, scarcity, susceptibility to dedifferentiation, and low quality, considering that the source of hepatocytes is usually liver biopsies obtained from individuals suffering from liver disease or material unsuitable for liver transplantation [ 193 , 196 , 197 , 198 , 199 ].…”

Section: Experimental Models and Methods To Study Hepatic Mitochondri...mentioning

confidence: 99%

Mitochondria as the Target of Hepatotoxicity and Drug-Induced Liver Injury: Molecular Mechanisms and Detection Methods

Mihajlovic

Vinken

2022

IJMS

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One of the major mechanisms of drug-induced liver injury includes mitochondrial perturbation and dysfunction. This is not a surprise, given that mitochondria are essential organelles in most cells, which are responsible for energy homeostasis and the regulation of cellular metabolism. Drug-induced mitochondrial dysfunction can be influenced by various factors and conditions, such as genetic predisposition, the presence of metabolic disorders and obesity, viral infections, as well as drugs. Despite the fact that many methods have been developed for studying mitochondrial function, there is still a need for advanced and integrative models and approaches more closely resembling liver physiology, which would take into account predisposing factors. This could reduce the costs of drug development by the early prediction of potential mitochondrial toxicity during pre-clinical tests and, especially, prevent serious complications observed in clinical settings.

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Section: Experimental Models and Methods To Study Hepatic Mitochondri...mentioning

confidence: 99%

Mitochondria as the Target of Hepatotoxicity and Drug-Induced Liver Injury: Molecular Mechanisms and Detection Methods

Mihajlovic

Vinken

2022

IJMS

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“…99,100 The 3D-scaffold model consists of hepatocytes supported by a scaffold material processed into a 3D shape. This 3D-shape is created by a controlled emulsification, lyophilization, solvent casting, salt leaching or gas foaming Primary human hepatocytes • Gold standard 13 • Dedifferentiation 34 36 and 37 • Representing population 33 • Availability 33 • Invasive • Time-consuming isolation 35 • Limited proliferation 33 HepG2…”

Section: Reviewmentioning

confidence: 99%

“…10 Cells used for the generation of such models are of various origin. Primary human hepatocytes (PHH) are the gold standard, [11][12][13] but even in 3D-culture conditions they are very difficult to culture for longer than one month while maintaining their functionality. Furthermore, their availability is rather limited.…”

Section: Introductionmentioning

confidence: 99%

The native liver as inspiration to create superior in vitro hepatic models

et al. 2023

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“…Primary human hepatocytes (PHHs) derived from liver tissue have been a source of physiologically relevant in vitro models for liver diseases, including MAFLD [ 41 , 44 , 45 , 70 , 73 , 80 , 81 , 91 , 94 , 95 , 96 ]. The PHH culture faithfully retains many molecular and cellular features of their in vivo counterparts and the disease phenotypes of the liver origin.…”

Section: Human Immortalized and Primary Cell Lines For Modeling Mafldmentioning

confidence: 99%

Advancements in MAFLD Modeling with Human Cell and Organoid Models

Wang

Yan

Chan

2022

IJMS

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Metabolic (dysfunction) associated fatty liver disease (MAFLD) is one of the most prevalent liver diseases and has no approved therapeutics. The high failure rates witnessed in late-phase MAFLD drug trials reflect the complexity of the disease, and how the disease develops and progresses remains to be fully understood. In vitro, human disease models play a pivotal role in mechanistic studies to unravel novel disease drivers and in drug testing studies to evaluate human-specific responses. This review focuses on MAFLD disease modeling using human cell and organoid models. The spectrum of patient-derived primary cells and immortalized cell lines employed to model various liver parenchymal and non-parenchymal cell types essential for MAFLD development and progression is discussed. Diverse forms of cell culture platforms utilized to recapitulate tissue-level pathophysiology in different stages of the disease are also reviewed.

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Primary hepatocyte cultures for liver disease modeling

Abstract: Word count (excluding references): 1617. Highlights:-Liver disease research relies to an important extent on the use of in vitro models.

Cited by 7 publications

References 44 publications

Mitochondria as the Target of Hepatotoxicity and Drug-Induced Liver Injury: Molecular Mechanisms and Detection Methods

Mitochondria as the Target of Hepatotoxicity and Drug-Induced Liver Injury: Molecular Mechanisms and Detection Methods

The native liver as inspiration to create superior in vitro hepatic models

Advancements in MAFLD Modeling with Human Cell and Organoid Models

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