ArticleStem cell research & therapy2024
Generation of human hepatobiliary organoids with a functional bile duct from chemically induced liver progenitor cells.
Article in Stem cell research & therapy, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed.
- Bioengineered Bile Duct for Liver Regenerative Medicine and Bile Duct Reconstruction.JGH open : an open access journal of gastroenterology and hepatology · 2025Review
- In vitro liver models for toxicological research.Drug metabolism and pharmacokinetics · 2025Review
- Organoids in biliary research: insights into developmental signaling and applications in disease modeling.Frontiers in cell and developmental biology · 2025Review
- The utilisation of biliary organoids for biomedical applications.Frontiers in bioengineering and biotechnology · 2024Review
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Authors and funding
15 authors.
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Abstract
backgroundLiver disease imposes a significant medical burden that persists due to a shortage of liver donors and an incomplete understanding of liver disease progression. Hepatobiliary organoids (HBOs) could provide an in vitro mini-organ model to increase the understanding of the liver and may benefit the development of regenerative medicine.
methodsIn this study, we aimed to establish HBOs with bile duct (BD) structures and mature hepatocytes (MHs) using human chemically induced liver progenitor cells (hCLiPs). hCLiPs were induced in mature cryo-hepatocytes using a small-molecule cocktail of TGF-β inhibitor (A-83-01, A), GSK3 inhibitor (CHIR99021, C), and 10% FBS (FAC). HBOs were then formed by seeding hCLiPs into ultralow attachment plates and culturing them with a combination of small molecules of Rock-inhibitor (Y-27632) and AC (YAC).
resultsThese HBOs exhibited bile canaliculi of MHs connected to BD structures, mimicking bile secretion and transportation functions of the liver. The organoids showed gene expression patterns consistent with both MHs and BD structures, and functional assays confirmed their ability to transport the bile analogs of rhodamine-123 and CLF. Functional patient-specific HBOs were also successfully created from hCLiPs sourced from cirrhotic liver tissues.
conclusionsThis study demonstrated the potential of human HBOs as an efficient model for studying hepatobiliary diseases, drug discovery, and personalized medicine.
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