Bioprinting of Human Liver-Derived Epithelial Organoids for Toxicity Studies.


Journal

Macromolecular bioscience
ISSN: 1616-5195
Titre abrégé: Macromol Biosci
Pays: Germany
ID NLM: 101135941

Informations de publication

Date de publication:
12 2021
Historique:
received: 02 09 2021
pubmed: 25 9 2021
medline: 30 3 2022
entrez: 24 9 2021
Statut: ppublish

Résumé

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.

Identifiants

pubmed: 34559943
doi: 10.1002/mabi.202100327
doi:

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

e2100327

Informations de copyright

© 2021 The Authors. Macromolecular Bioscience published by Wiley-VCH GmbH.

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Auteurs

Manon C Bouwmeester (MC)

Department of Clinical Sciences, Faculty of Veterinary Medicine, Regenerative Medicine Center Utrecht, Utrecht University, Uppsalalaan 8, Utrecht, 3584 CT, The Netherlands.

Paulina N Bernal (PN)

Department of Orthopaedics, Regenerative Medicine Center Utrecht, University Medical Center Utrecht, Uppsalalaan 8, Utrecht, 3584 CT, The Netherlands.

Loes A Oosterhoff (LA)

Department of Clinical Sciences, Faculty of Veterinary Medicine, Regenerative Medicine Center Utrecht, Utrecht University, Uppsalalaan 8, Utrecht, 3584 CT, The Netherlands.

Monique E van Wolferen (ME)

Department of Clinical Sciences, Faculty of Veterinary Medicine, Regenerative Medicine Center Utrecht, Utrecht University, Uppsalalaan 8, Utrecht, 3584 CT, The Netherlands.

Vivian Lehmann (V)

Department of Clinical Sciences, Faculty of Veterinary Medicine, Regenerative Medicine Center Utrecht, Utrecht University, Uppsalalaan 8, Utrecht, 3584 CT, The Netherlands.
Division of Pediatric Gastroenterology, Wilhelmina Children's Hospital, Regenerative Medicine Center Utrecht, Uppsalalaan 8, Utrecht, 3584 CT, The Netherlands.

Monique Vermaas (M)

Department of Clinical Sciences, Faculty of Veterinary Medicine, Regenerative Medicine Center Utrecht, Utrecht University, Uppsalalaan 8, Utrecht, 3584 CT, The Netherlands.

Maj-Britt Buchholz (MB)

Department of Clinical Sciences, Faculty of Veterinary Medicine, Regenerative Medicine Center Utrecht, Utrecht University, Uppsalalaan 8, Utrecht, 3584 CT, The Netherlands.

Quentin C Peiffer (QC)

Department of Orthopaedics, Regenerative Medicine Center Utrecht, University Medical Center Utrecht, Uppsalalaan 8, Utrecht, 3584 CT, The Netherlands.

Jos Malda (J)

Department of Clinical Sciences, Faculty of Veterinary Medicine, Regenerative Medicine Center Utrecht, Utrecht University, Uppsalalaan 8, Utrecht, 3584 CT, The Netherlands.
Department of Orthopaedics, Regenerative Medicine Center Utrecht, University Medical Center Utrecht, Uppsalalaan 8, Utrecht, 3584 CT, The Netherlands.

Luc J W van der Laan (LJW)

Department of Surgery, Erasmus Medical Center, Postbus 2040, Rotterdam, 3000 CA, The Netherlands.

Nynke I Kramer (NI)

Institute for Risk Assessment Sciences, Utrecht University, Yalelaan 2, Utrecht, 3584 CM, The Netherlands.
Division of Toxicology, Wageningen University, P.O. box 8000, Wageningen, 6700 EA, The Netherlands.

Kerstin Schneeberger (K)

Department of Clinical Sciences, Faculty of Veterinary Medicine, Regenerative Medicine Center Utrecht, Utrecht University, Uppsalalaan 8, Utrecht, 3584 CT, The Netherlands.

Riccardo Levato (R)

Department of Clinical Sciences, Faculty of Veterinary Medicine, Regenerative Medicine Center Utrecht, Utrecht University, Uppsalalaan 8, Utrecht, 3584 CT, The Netherlands.
Department of Orthopaedics, Regenerative Medicine Center Utrecht, University Medical Center Utrecht, Uppsalalaan 8, Utrecht, 3584 CT, The Netherlands.

Bart Spee (B)

Department of Clinical Sciences, Faculty of Veterinary Medicine, Regenerative Medicine Center Utrecht, Utrecht University, Uppsalalaan 8, Utrecht, 3584 CT, The Netherlands.

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