ArticleJournal of biological engineering2020
Tubular bile duct structure mimicking bile duct morphogenesis for prospective in vitro liver metabolite recovery.
Article in Journal of biological engineering, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 12 citations in OpenAlex.
- Generation of human hepatobiliary organoids with a functional bile duct from chemically induced liver progenitor cells.Stem cell research & therapy · 2024Article
- Evidence for in vitro extensive proliferation of adult hepatocytes and biliary epithelial cells.Stem cell reports · 2023Article
- Evidence forbioRxiv : the preprint server for biology · 2023Article
- Live functional assays reveal longitudinal maturation of transepithelial transport in kidney organoids.Frontiers in cell and developmental biology · 2022Article
- [A review on cell-based models of human liver disease in vitro].Sheng wu yi xue gong cheng xue za zhi = Journal of biomedical engineering = Shengwu yixue gongchengxue zazhi · 2021Review
- Development of liver microtissues with functional biliary ductular network.Biotechnology and bioengineering · 2021Article
- Prospect ofFrontiers in toxicology · 2021Review
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundLiver metabolites are used to diagnose disease and examine drugs in clinical pharmacokinetics. Therefore, development of an in vitro assay system that reproduces liver metabolite recovery would provide important benefits to pharmaceutical research. However, liver models have proven challenging to develop because of the lack of an appropriate bile duct structure for the accumulation and transport of metabolites from the liver parenchyma. Currently available bile duct models, such as the bile duct cyst-embedded extracellular matrix (ECM), lack any morphological resemblance to the tubular morphology of the living bile duct. Moreover, these systems cannot overcome metabolite recovery issues because they are established in isolated culture systems. Here, we successfully established a non-continuous tubular bile duct structure model in an open-culture system, which closely resembled an in vivo structure. This system was utilized to effectively collect liver metabolites separately from liver parenchymal cells.
resultsTriple-cell co-culture of primary rat hepatoblasts, rat biliary epithelial cells, and mouse embryonic fibroblasts was grown to mimic the morphogenesis of the bile duct during liver development. Overlaying the cells with ECM containing a Matrigel and collagen type I gel mixture promoted the development of a tubular bile duct structure. In this culture system, the expression of specific markers and signaling molecules related to biliary epithelial cell differentiation was highly upregulated during the ductal formation process. This bile duct structure also enabled the separate accumulation of metabolite analogs from liver parenchymal cells.
conclusionsA morphogenesis-based culture system effectively establishes an advanced bile duct structure and improves the plasticity of liver models feasible for autologous in vitro metabolite-bile collection, which may enhance the performance of high-throughput liver models in cell-based assays.
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