Inter-individual differences in the susceptibility of primary human hepatocytes towards drug-induced cholestasis are compound and time dependent

Parmentier, Céline; Hendriks, Delilah; Heyd, Bruno; Bachellier, Philippe; Ingelman‐Sundberg, Magnus; Richert, Lysiane

doi:10.1016/j.toxlet.2018.06.1069

Cited by 17 publications

(22 citation statements)

References 315 publications

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“…In addition, 3D PHH spheroids have been used for predicting drug-induced changes in BA transport and hepatocellular toxicity. Highest sensitivity is seen during prolonged incubation time of the spheroids in the presence of exogenous BAs and the drug and sensitivity might be somewhat improved 100,101 .…”

Section: Transporters In Drug-and Bile Acid (Ba)-induced Liver Injurymentioning

confidence: 99%

Managing the challenge of drug-induced liver injury: a roadmap for the development and deployment of preclinical predictive models

Weaver

Blomme

Chadwick

et al. 2019

Nat Rev Drug Discov

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154

148

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Drug-induced liver injury (DILI) is a patient-specific, temporal, multifactorial pathophysiological process that cannot yet be recapitulated in a single in vitro model. Current pre-clinical testing regimes for the detection of human DILI thus remain inadequate. A systematic and concerted research effort is required to address the deficiencies in current models and to present a defined approach towards the development of new or adapted model systems for DILI prediction. This Perspective defines the current status of available models and mechanistic understanding of DILI, and proposes our vision of a roadmap for the development of predictive preclinical models of human DILI.

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Section: Transporters In Drug-and Bile Acid (Ba)-induced Liver Injurymentioning

confidence: 99%

Managing the challenge of drug-induced liver injury: a roadmap for the development and deployment of preclinical predictive models

Weaver

Blomme

Chadwick

et al. 2019

Nat Rev Drug Discov

Self Cite

154

148

View full text Add to dashboard Cite

show abstract

“…PHH re‐establish bile canalicular networks when cultured in sandwich culture or spheroid culture, and PHH spheroids were able to discriminate cholestatic hepatotoxins from hepatotoxins with other mechanisms of injury . Importantly, identification of the cholestatic liability of drugs improved upon prolonged exposure . Precision‐cut human liver slices have also been shown responsive to typical cholestatic compounds with appropriate transcriptomic signatures .…”

Section: Applications Of Advanced Primary Human Hepatocyte Culture Momentioning

confidence: 99%

3D Primary Hepatocyte Culture Systems for Analyses of Liver Diseases, Drug Metabolism, and Toxicity: Emerging Culture Paradigms and Applications

Lauschke

Shafagh

Hendriks

et al. 2019

Biotechnology Journal

101

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Recent research has shown that the maintenance of relevant liver functions ex vivo requires models in which the cells exhibit an in vivo‐like phenotype, often achieved by reconstitution of appropriate cellular interactions. Multiple different models have been presented that differ in the cells utilized, media, and culture conditions. Furthermore, several technologically different approaches have been presented including bioreactors, chips, and plate‐based systems in fluidic or static media constituting of chemically diverse materials. Using such models, the ability to predict drug metabolism, drug toxicity, and liver functionality have increased tremendously as compared to conventional in vitro models in which cells are cultured as 2D monolayers. Here, the authors highlight important considerations for microphysiological systems for primary hepatocyte culture, review current culture paradigms, and discuss their opportunities for studies of drug metabolism, hepatotoxicity, liver biology, and disease.

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“…Such in vitro models include, but are not limited to, spheroid cultures as well as sandwich cultures of primary hepatocytes [ 361 , 362 , 363 ]. They have been shown most appropriate for testing liver-specific toxicity [ 118 , 339 , 364 , 365 ]. Stem cell-based in vitro models have emerged over the past 2 decades [ 366 , 367 ].…”

Section: Critical Parameters For Practical In Vitro Liver Toxicity Testingmentioning

confidence: 99%

In Vitro Liver Toxicity Testing of Chemicals: A Pragmatic Approach

Tabernilla

Rodrigues

Pieters

et al. 2021

IJMS

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The liver is among the most frequently targeted organs by noxious chemicals of diverse nature. Liver toxicity testing using laboratory animals not only raises serious ethical questions, but is also rather poorly predictive of human safety towards chemicals. Increasing attention is, therefore, being paid to the development of non-animal and human-based testing schemes, which rely to a great extent on in vitro methodology. The present paper proposes a rationalized tiered in vitro testing strategy to detect liver toxicity triggered by chemicals, in which the first tier is focused on assessing general cytotoxicity, while the second tier is aimed at identifying liver-specific toxicity as such. A state-of-the-art overview is provided of the most commonly used in vitro assays that can be used in both tiers. Advantages and disadvantages of each assay as well as overall practical considerations are discussed.

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Inter-individual differences in the susceptibility of primary human hepatocytes towards drug-induced cholestasis are compound and time dependent

Cited by 17 publications

References 315 publications

Managing the challenge of drug-induced liver injury: a roadmap for the development and deployment of preclinical predictive models

Managing the challenge of drug-induced liver injury: a roadmap for the development and deployment of preclinical predictive models

3D Primary Hepatocyte Culture Systems for Analyses of Liver Diseases, Drug Metabolism, and Toxicity: Emerging Culture Paradigms and Applications

In Vitro Liver Toxicity Testing of Chemicals: A Pragmatic Approach

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