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Cited by 62Drug-Induced Hepatotoxicity and ProtectionLiver physiology and pathology3D Printing in Biomedical Research

3D human liver spheroids for translational pharmacology and toxicology

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Ingelman‐Sundberg, Magnus, Lauschke, Volker M.·2022·Basic & Clinical Pharmacology & Toxicology
DOI 10.1111/bcpt.13587
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Abstract

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.

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  • This work contributes to reducing reliance on animal testing and promoting ethical innovation in preclinical research.

    “this work contributes to reducing reliance on animal testing and promoting ethical innovation in preclinical research, as emphasized by Ingelman-Sundberg and Lauschke43.”

    From ​Temporal proteomic profiling of iPSC-derived human liver organoids reveals optimal maturation for drug metabolism and toxicology (2026) · cites this paper as [43]

    The Introduction and Conclusions describe human liver spheroids as tools for preclinical pharmacology and toxicology. Neither section says they reduce reliance on animal testing or discusses an ethical benefit; searches for animal testing, replacement, and ethics found no such passage in our copy. (LLM, conf=0.72)

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  • Spheroid culture formats are reasonably easy to use, reproducible, allow medium to high throughput screening, and have shown vast improvements in retention of mature phenotypes compared to 2D adhesion cultures.

    “Spheroid culture formats are reasonably easy to use, reproducible, allow medium to high throughput screening, and have shown vast improvements in retention of mature phenotypes compared to 2D adhesion cultures [10] .”

    From 3D microperfusion of mesoscale human microphysiological liver models improves functionality and recapitulates hepatic zonation (2023) · cites this paper as [10]

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Cited by

Sorted by citations

Authors
Ingelman‐Sundberg, M., & Lauschke, V. M.
Affiliations
Karolinska Institutet (SE)
Corresponding author
Lauschke, Volker M.
ORCID
Venue
Basic & Clinical Pharmacology & Toxicology
Publisher
Wiley
Published
2021-05-04
Volume
130
Issue
S1
Pages
5-15
ISSN
  • 1742-7835 (ISSN-L)
  • 1742-7843
DOI
10.1111/bcpt.13587
OpenAlex
W3153323717
Cited by
62
References
12
Citations by year
2026: 11 · 2025: 14 · 2024: 11 · 2023: 15 · 2022: 7 · 2021: 4
FWCI
1.64
Type
journal article
Language
en
Open access
Licence
Locations
  • Basic & Clinical Pharmacology & Toxicology (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
Funders
  • Innovative Medicines Initiative (875510)
  • Vetenskapsrådet (2015‐02760, 2016‐01153, 2016‐01154, 2019‐01837)
  • H2020 European Research Council (742020)
  • Cancerfonden (17 0599)
Topics
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Drug-Induced Hepatotoxicity and Protection
  • Health Sciences › Medicine › Hepatology › Liver physiology and pathology
  • Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
Keywords
hepatotoxicity, drug toxicity prediction, hepatic drug metabolism, drug disposition, nonalcoholic steatohepatitis, liver fibrosis, malaria, viral hepatitis, chronic liver disease, translational toxicology, translational pharmacology
MeSH terms
Drug Development, Animals, Humans, Liver, Liver Diseases, Pharmacology, Toxicology, Spheroids, Cellular, Chemical and Drug Induced Liver Injury, Translational Research, Biomedical

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