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

Autor: Willemse J; Department of Surgery, Transplant Institute, Erasmus MC, University Medical Center Rotterdam, the Netherlands., van Tienderen G; Department of Surgery, Transplant Institute, Erasmus MC, University Medical Center Rotterdam, the Netherlands., van Hengel E; Department of Surgery, Transplant Institute, Erasmus MC, University Medical Center Rotterdam, the Netherlands., Schurink I; Department of Surgery, Transplant Institute, Erasmus MC, University Medical Center Rotterdam, the Netherlands., van der Ven D; Department of Surgery, Transplant Institute, Erasmus MC, University Medical Center Rotterdam, the Netherlands., Kan Y; Department of Surgery, Transplant Institute, Erasmus MC, University Medical Center Rotterdam, the Netherlands., de Ruiter P; Department of Surgery, Transplant Institute, Erasmus MC, University Medical Center Rotterdam, the Netherlands., Rosmark O; Lung Biology, Department Experimental Medical Science, Lund University, Lund, Sweden., Westergren-Thorsson G G; Lung Biology, Department Experimental Medical Science, Lund University, Lund, Sweden., Schneeberger K; Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, Utrecht, the Netherlands., van der Eerden B; Department of Internal Medicine, Calcium and Bone Metabolism, Erasmus MC-University, Rotterdam, the Netherlands., Roest H; Department of Surgery, Transplant Institute, Erasmus MC, University Medical Center Rotterdam, the Netherlands., Spee B; Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, Utrecht, the Netherlands., van der Laan L; Department of Surgery, Transplant Institute, Erasmus MC, University Medical Center Rotterdam, the Netherlands., de Jonge J; Department of Surgery, Transplant Institute, Erasmus MC, University Medical Center Rotterdam, the Netherlands., Verstegen M; Department of Surgery, Transplant Institute, Erasmus MC, University Medical Center Rotterdam, the Netherlands. Electronic address: m.verstegen@ermasmusmc.nl.
Jazyk: angličtina
Zdroj: Biomaterials [Biomaterials] 2022 May; Vol. 284, pp. 121473. Date of Electronic Publication: 2022 Mar 24.
DOI: 10.1016/j.biomaterials.2022.121473
Abstrakt: 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.
(Copyright © 2022. Published by Elsevier Ltd.)
Databáze: MEDLINE
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