Cited by 6Liver physiology and pathologyLiver Disease Diagnosis and TreatmentDrug-Induced Hepatotoxicity and Protection

Live-cell imaging of human liver fibrosis using hepatic micro-organoids

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Guan, Yuan, Fang, Zhuoqing, Hu, Angelina, Roberts, Sarah, Wang, Meiyue, Ren, Wenlong, Johansson, Patrik K., Heilshorn, Sarah C. +2 more·2025·JCI Insight

Abstract

Due to the limitations of available in vitro systems and animal models, we lack a detailed understanding of the pathogenetic mechanisms of and have minimal treatment options for liver fibrosis. Therefore, we engineered a live-cell imaging system that assessed fibrosis in a human multilineage hepatic organoid in a microwell (i.e., microHOs). Transcriptomic analysis revealed that TGFB converted mesenchymal cells in microHOs into myofibroblast-like cells resembling those in fibrotic human liver tissue. When pro-fibrotic intracellular signaling pathways were examined, the antifibrotic effect of receptor-specific tyrosine kinase inhibitors was limited to the fibrosis induced by the corresponding growth factor, which indicates their antifibrotic efficacy would be limited to fibrotic diseases solely mediated by that growth factor. Based upon transcriptomic and transcription factor activation analyses in microHOs, glycogen synthase kinase 3β and p38 MAPK inhibitors were identified as potential new broad-spectrum therapies for liver fibrosis. Other new therapies could subsequently be identified using the microHO system.

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  • Day 21 or around this timepoint has been identified as an important stage for liver organoid functional development in several previous studies.

    “It is also noteworthy that Day 21, or around this timepoint, has been identified as an important stage for liver organoid functional development in several previous studies13,15,28,29.”

    From ​Temporal proteomic profiling of iPSC-derived human liver organoids reveals optimal maturation for drug metabolism and toxicology (2026) · cites this paper as [28]

    The Results section (“A high-content screening system”) calls day-21 organoids mature and reports receptor expression at that timepoint, supporting a connection between day 21 and organoid maturation. It does not identify day 21 as an important stage specifically for functional development; its day-21 evidence concerns receptor expression. (LLM, conf=0.78)

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Cited by

Sorted by citations

Authors
Guan, Y., Fang, Z., Hu, A., Roberts, S., Wang, M., Ren, W., Johansson, P. K., Heilshorn, S. C., Enejder, A., & Peltz, G.
Affiliations
  • Stanford Medicine (US)
  • Stanford University (US)
Corresponding author
Peltz, Gary
Venue
JCI Insight
Published
2024-12-10
Volume
10
Issue
2
ISSN
2379-3708 (ISSN-L)
OpenAlex
W4405236007
Cited by
6
References
13
Citations by year
2026: 4 · 2025: 2
FWCI
1.55
Type
journal article
Language
en
Open access
Locations
  • JCI Insight (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • NIH Office of the Director (1R56DK129309A1)
  • National Science Foundation (CBET 2033302)
Topics
  • Health Sciences › Medicine › Hepatology › Liver physiology and pathology
  • Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Drug-Induced Hepatotoxicity and Protection
Keywords
liver fibrosis, hepatic organoids, live-cell imaging, TGF-beta signaling, myofibroblast differentiation, mesenchymal cells, tyrosine kinase inhibitors, glycogen synthase kinase-3β, p38 MAPK, antifibrotic therapy, gene expression profiling, transcription factor activation
MeSH terms
Glycogen Synthase Kinase 3 beta, Humans, Liver, Liver Cirrhosis, Organoids, Signal Transduction, Protein Kinase Inhibitors, p38 Mitogen-Activated Protein Kinases, Myofibroblasts, Mesenchymal Stem Cells

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