ArticleAdvanced materials interfaces2021
Elucidating Extracellular Matrix and Stiffness Control of Primary Human Hepatocyte Phenotype Via Cell Microarrays.
Article in Advanced materials interfaces, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
11 citing papers in PubMed, 13 citations in OpenAlex.
- Micro Pattern-Based 3D Cell Culture Platform: An Overview of Technologies and Applications.Exploration (Beijing, China) · 2026Review
- Spatial patterning strategies for liver tissue engineering: Biofabrication technologies and applications.Advanced drug delivery reviews · 2026Review
- Advances in drug-induced liver injury research: in vitro models, mechanisms, omics and gene modulation techniques.Cell & bioscience · 2024Review
- Advances in high throughput cell culture technologies for therapeutic screening and biological discovery applications.Bioengineering & translational medicine · 2024Review
- Combinatorial Microgels for 3D ECM Screening and Heterogeneous Microenvironmental Culture of Primary Human Hepatic Stellate Cells.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Decellularized Liver Nanofibers Enhance and Stabilize the Long-Term Functions of Primary Human Hepatocytes In Vitro.Advanced healthcare materials · 2023Article
- Combinatorial Microgels for 3D ECM Screening and Heterogeneous Microenvironmental Culture of Primary Human Hepatic Stellate Cells.bioRxiv : the preprint server for biology · 2023Article
- Regulators, functions, and mechanotransduction pathways of matrix stiffness in hepatic disease.Frontiers in physiology · 2023Review
- Engineered matrix microenvironments reveal the heterogeneity of liver sinusoidal endothelial cell phenotypic responses.APL bioengineering · 2022Article
- Modulation of human iPSC-derived hepatocyte phenotype via extracellular matrix microarrays.Acta biomaterialia · 2022Article
- An Engineered Protein-Based Building Block (Albumin Methacryloyl) for Fabrication of a 3D In Vitro Cryogel Model.Gels (Basel, Switzerland) · 2022Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
How the liver's extracellular matrix (ECM) protein composition and stiffness cooperatively regulate primary human hepatocyte (PHH) phenotype is unelucidated. Here, we utilize protein microarrays and high content imaging with single-cell resolution to assess PHH attachment/functions on 10 major liver ECM proteins in single and two-way combinations robotically spotted onto polyacrylamide gels of 1 kPa or 25 kPa stiffness. Albumin, cytochrome-P450 3A4 (CYP3A4), and hepatocyte nuclear factor alpha (HNF4α) positively correlate with each other and cell density on both stiffnesses. The 25 kPa stiffness supports higher average albumin and HNF4α expression after 14 days, while ECM protein composition significantly modulates PHH functions across both stiffnesses. Unlike previous rodent data, PHH functions are highest only when collagen-IV or fibronectin are mixed with specific proteins, whereas non-collagenous proteins without mixed collagens downregulate functions. Combination of collagen-IV and hyaluronic acid retains high CYP3A4 on 1 kPa, whereas collagens-IV and -V better retain HNF4α on 25 kPa over 14 days. Adapting ECM conditions to 96-well plates containing conjugated hydrogels reveals novel regulation of other functions (urea, CYP1A2/2A6/2C9) and drug-mediated CYP induction by the ECM protein composition/stiffness. This high-throughput pipeline can be adapted to elucidate ECM's role in liver diseases and facilitate optimization of engineered tissues.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.