3D human liver spheroids for translational pharmacology and toxicology.
NASH
drug development
drug discovery
hepatotoxicity
organotypic culture
pharmacokinetics
Journal
Basic & clinical pharmacology & toxicology
ISSN: 1742-7843
Titre abrégé: Basic Clin Pharmacol Toxicol
Pays: England
ID NLM: 101208422
Informations de publication
Date de publication:
Jan 2022
Jan 2022
Historique:
revised:
12
04
2021
received:
10
03
2021
accepted:
13
04
2021
pubmed:
20
4
2021
medline:
25
3
2022
entrez:
19
4
2021
Statut:
ppublish
Résumé
Drug development is a failure-prone endeavour, and more than 85% of drugs fail during clinical development, showcasing that current preclinical systems for compound selection are clearly inadequate. Liver toxicity remains a major reason for safety failures. Furthermore, all efforts to develop pharmacological therapies for a variety of chronic liver diseases, such as non-alcoholic steatohepatitis (NASH) and fibrosis, remain unsuccessful. Considering the time and expense of clinical trials, as well as the substantial burden on patients, new strategies are thus of paramount importance to increase clinical success rates. To this end, human liver spheroids are becoming increasingly utilized as they allow to preserve patient-specific phenotypes and functions for multiple weeks in culture. We here review the recent application of such systems for i) predictive and mechanistic analyses of drug hepatotoxicity, ii) the evaluation of hepatic disposition and metabolite formation of low clearance drugs and iii) the development of drugs for metabolic and infectious liver diseases, including NASH, fibrosis, malaria and viral hepatitis. We envision that with increasing dissemination, liver spheroids might become the new gold standard for such applications in translational pharmacology and toxicology.
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
5-15Subventions
Organisme : Innovative Medicines Initiative
ID : 875510
Organisme : Vetenskapsrådet
ID : 2015-02760
Organisme : Vetenskapsrådet
ID : 2016-01153
Organisme : Vetenskapsrådet
ID : 2016-01154
Organisme : Vetenskapsrådet
ID : 2019-01837
Organisme : H2020 European Research Council
ID : 742020
Organisme : Cancerfonden
ID : 17 0599
Informations de copyright
© 2021 The Authors. Basic & Clinical Pharmacology & Toxicology published by John Wiley & Sons Ltd on behalf of Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).
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