Bioprinting of Human Liver-derived Epithelial Organoids for Toxicity Studies

Autor: Bouwmeester, Manon C, Bernal, Paulina Nunez, Oosterhoff, Loes A, van Wolferen, Monique, Lehmann, Vivian, Vermaas, Monique, Buchholz, Maj-Britt, Peiffer, Quentin, Malda, Jos, van der Laan, Luc J W, Kramer, Nynke I, Schneeberger, Kerstin, Levato, Riccardo, Spee, Bart, Interne geneeskunde GD, dCSCA RMSC-1, Equine Musculoskeletal Biology, dES RMSC, dIRAS RA-1, CS_STEM
Přispěvatelé: Interne geneeskunde GD, dCSCA RMSC-1, Equine Musculoskeletal Biology, dES RMSC, dIRAS RA-1, CS_STEM, Surgery
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: Macromolecular Bioscience, 21(12), 1. Wiley-VCH Verlag
Macromolecular Bioscience 21 (2021) 12
Macromolecular Bioscience
Macromolecular Bioscience, 21(12)
Macromolecular Bioscience, 21(12):2100327. Wiley-VCH
ISSN: 1616-5187
Popis: There is a need for long-lived hepatic in vitro models to better predict drug induced liver injury (DILI). Human liver-derived epithelial organoids are a promising cell source for advanced in vitro models. Here, organoid technology is combined with biofabrication techniques, which holds great potential for the design of in vitro models with complex and customizable architectures. Here, porous constructs with human hepatocyte-like cells derived from organoids are generated using extrusion-based printing technology. Cell viability of bioprinted organoids remains stable for up to ten days (88–107% cell viability compared to the day of printing). The expression of hepatic markers, transporters, and phase I enzymes increased compared to undifferentiated controls, and is comparable to non-printed controls. Exposure to acetaminophen, a well-known hepatotoxic compound, decreases cell viability of bioprinted liver organoids to 21–51% (p < 0.05) compared to the start of exposure, and elevated levels of damage marker miR-122 are observed in the culture medium, indicating the potential use of the bioprinted constructs for toxicity testing. In conclusion, human liver-derived epithelial organoids can be combined with a biofabrication approach, thereby paving the way to create perfusable, complex constructs which can be used as toxicology- and disease-models.
Databáze: OpenAIRE