Hydrogels derived from decellularized liver tissue support the growth and differentiation of cholangiocyte organoids
Open accessAbstract
Human cholangiocyte organoids are promising for regenerative medicine applications, such as repair of damaged bile ducts. However, organoids are typically cultured in mouse tumor-derived basement membrane extracts (BME), which is poorly defined, highly variable and limits the direct clinical applications of organoids in patients. Extracellular matrix (ECM)-derived hydrogels prepared from decellularized human or porcine livers are attractive alternative culture substrates. Here, the culture and expansion of human cholangiocyte organoids in liver ECM(LECM)-derived hydrogels is described. These hydrogels support proliferation of cholangiocyte organoids and maintain the cholangiocyte-like phenotype. The use of LECM hydrogels does not significantly alter the expression of selected genes or proteins, such as the cholangiocyte marker cytokeratin-7, and no species-specific effect is found between human or porcine LECM hydrogels. Proliferation rates of organoids cultured in LECM hydrogels are lower, but the differentiation capacity of the cholangiocyte organoids towards hepatocyte-like cells is not altered by the presence of tissue-specific ECM components. Moreover, human LECM extracts support the expansion of ICO in a dynamic culture set up without the need for laborious static culture of organoids in hydrogel domes. Liver ECM hydrogels can successfully replace tumor-derived BME and can potentially unlock the full clinical potential of human cholangiocyte organoids.
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Rheological data always showed storage modulus (G′) values higher than loss modulus (G′′) values, typical stable gel behavior.
“Rheological data always showed storage modulus (G′) values higher than loss modulus (G″) values, typical stable gel behavior.”
G′ values depended on ECM concentration (usually 5-20 mg/mL) and crosslinking method.
“G′ values quoted ranged between ∼100 Pa and in excess of 5000 Pa and depended on the concentration of the ECM (usually 5–20 mg/mL) and the crosslinking method [23,24].”
G′ values ranged between ∼100 Pa and in excess of 5000 Pa.
“G′ values quoted ranged between ∼100 Pa and in excess of 5000 Pa and depended on the concentration of the ECM (usually 5–20 mg/mL) and the crosslinking method [23,24].”
Turbidity measurements indicated a concentration-dependent initial lag followed by increasing turbidity, characteristic of collagen fibrillogenesis.
“Turbide measurements indicated a concentration-dependent initial lag followed by the formation of increasing turbide, characteristic of collagen fibrillogenesis [23].”
dLECM has potential as a better-than-Matrigel alternative culture system for organoid cultures, providing xenogeneic-free, tissue-specific niche that supports growth of cholangiocyte and hepatocyte organoids without risk profile of tumor-derived matrices.
“In addition, dLECM has been shown to have the potential as a better-than-Matrigel alternative culture system for organoid cultures that provides a xenogeneic-free, tissue-specific niche that supports the growth of cholangiocyte and hepatocyte organoids without the risk profile seen with tumor-derived matrices [23].”
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- Authors
- Willemse, J., van Tienderen, G., van Hengel, E., Schurink, I., van der Ven, D., Kan, Y., de Ruiter, P., Rosmark, O., Westergren-Thorsson G, G., Schneeberger, K., van der Eerden, B., Roest, H., Spee, B., van der Laan, L., de Jonge, J., & Verstegen, M.
- Affiliations
- Erasmus MC (NL)
- Lund University (SE)
- Utrecht University (NL)
- Corresponding author
- Verstegen, Monique
- ORCID
- Venue
- Biomaterials
- Publisher
- Elsevier BV
- Published
- 2022-05
- Volume
- 284
- Pages
- 121473
- ISSN
- 0142-9612 (ISSN-L)
- OpenAlex
- W4220784575
- Cited by
- 106
- References
- 75
- Citations by year
- 2026: 9 · 2025: 37 · 2024: 32 · 2023: 22 · 2022: 6
- FWCI
- 23.16
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Biomaterials (publishedVersion, cc-by)
- PubMed (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (publishedVersion, cc-by)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion, cc-by)
- Utrecht University Repository (Utrecht University) (submittedVersion, other-oa)
- Lund University Publications (Lund University) (submittedVersion)
- Funders
- University of Twente
- Medical Delta
- Topics
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Hydrogels: synthesis, properties, applications
- Keywords
- cholangiocyte organoids, hydrogels, bile duct regeneration, CK7, regenerative medicine
- MeSH terms
- Animals, Extracellular Matrix, Humans, Liver, Neoplasms, Organoids, Plant Extracts, Swine, Hydrogels, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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