Cited by 107Tissue Engineering and Regenerative Medicine3D Printing in Biomedical ResearchHydrogels: synthesis, properties, applications

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Hydrogels derived from decellularized liver tissue support the growth and differentiation of cholangiocyte organoids

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Willemse, Jorke, van Tienderen, Gilles, van Hengel, Eline, Schurink, Ivo, van der Ven, Diana, Kan, Yik, de Ruiter, Petra, Rosmark, Oskar, Westergren-Thorsson G, Gunilla, Schneeberger, Kerstin, van der Eerden, Bram, Roest, Henk, Spee, Bart, van der Laan, Luc, de Jonge, Jeroen, Verstegen, Monique·2022·Biomaterials

DOI 10.1016/j.biomaterials.2022.121473

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Abstract

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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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: Willemse, Jorke
van Tienderen, Gilles
van Hengel, Eline
Schurink, Ivo
van der Ven, Diana
Kan, Yik
de Ruiter, Petra
Rosmark, Oskar
Schneeberger, Kerstin
van der Eerden, Bram
Roest, Henk
Spee, Bart
van der Laan, Luc
de Jonge, Jeroen
Verstegen, Monique
Venue: Biomaterials
Publisher: Elsevier BV
Published: 2022-05
Volume: 284
Pages: 121473
ISSN: 0142-9612 (ISSN-L)
DOI: 10.1016/j.biomaterials.2022.121473
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: cc-by
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
creativecommons.org/licenses/by/4.0/ (vor)
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
Physical Sciences › Materials Science › Biomaterials › 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

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Hydrogels derived from decellularized liver tissue support the growth and differentiation of cholangiocyte organoids

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