Advancements in MAFLD Modeling with Human Cell and Organoid Models
Open accessAbstract
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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Limited translation of preclinical data from animal models due to interspecies differences increases the importance of human-oriented in vitro platforms compatible with controlled design and high-throughput screening.
“Against the background of the limited translation of preclinical data from animal models due to interspecies differences, the importance of human-oriented in vitro platforms compatible with controlled design and high-throughput screening is increasing.”
From The HepG2 Cell Line as a Model for Studying Metabolic Dysfunction-Associated Steatotic Liver Disease (2026) · cites this paper as [27]
Section 1.4 says species-specific differences may hinder translation from animal MAFLD models and calls human in vitro models critical. The Concluding Remarks identify high-throughput drug screening as an application, while Section 4.1 describes precise control of microfluidic models but says their low throughput makes high-throughput screening challenging. The claim therefore overgeneralizes the combination of controlled design and high-throughput compatibility. (LLM, conf=0.85)
Experimental — accuracy not yet measuredThe advantages of the MASLD model in HepG2 include reproducibility, preservation of key lipid metabolism pathways, high transfection efficiency, suitability for high-throughput screening, rapid lipid accumulation upon exposure to saturated fatty acids, and low cost.
“The advantages of the MASLD model in this cell line include reproducibility, preservation of key lipid metabolism pathways, high transfection efficiency, suitability for high-throughput screening (HTS), rapid lipid accumulation upon exposure to SFA, low cost, etc. [27,29,79].”
From The HepG2 Cell Line as a Model for Studying Metabolic Dysfunction-Associated Steatotic Liver Disease (2026) · cites this paper as [27]
Section 2.1 (page not specified) describes HepG2 as a stable, widely used MAFLD model and reports lipid accumulation after oleic-acid treatment, including models co-treated with saturated fatty acids. Section 2 also describes stable cell lines as suitable for genetic perturbation. The copy does not establish the claimed high transfection efficiency, preservation of key lipid-metabolism pathways, HepG2-specific high-throughput suitability, rapid lipid accumulation specifically upon saturated-fatty-acid exposure, or low cost. (LLM, conf=0.86)
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- Authors
- Wang, S.-X., Yan, J.-S., & Chan, Y.-S.
- Affiliations
- Guangzhou Laboratory, No. 9 Xing Dao Huan Bei Road, Guangzhou International Bio Island, Guangzhou 510005, China
- Yunnan University (CN)
- Guangzhou Laboratory (CN)
- Corresponding author
- Chan, Yun-Shen
- ORCID
- Chan, Yun-Shen
- Venue
- International Journal of Molecular Sciences
- Publisher
- MDPI AG
- Published
- 2022-10-06
- Volume
- 23
- Issue
- 19
- Pages
- 11850
- ISSN
- 1422-0067 (ISSN-L)
- PMC
- PMC9569457
- OpenAlex
- W4303699718
- Cited by
- 22
- References
- 202
- Citations by year
- 2026: 5 · 2025: 3 · 2024: 8 · 2023: 6
- FWCI
- 0.68
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- International Journal of Molecular Sciences (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Drug-Induced Hepatotoxicity and Protection
- Keywords
- non-alcoholic fatty liver disease, disease modeling, human organoids, patient-derived primary cells, immortalized cell lines, liver parenchymal cells, non-parenchymal liver cells, in vitro disease model, drug testing, disease progression
- MeSH terms
- Humans, Liver Diseases, Organoids, Cell Culture Techniques, Non-alcoholic Fatty Liver Disease
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