Bioprinting of Human Liver-Derived Epithelial Organoids for Toxicity Studies

Manon C. Bouwmeester, Paulina N. Bernal, Loes A. Oosterhoff, Monique E. van Wolferen, Vivian Lehmann, Monique Vermaas, Maj Britt Buchholz, Quentin C. Peiffer, Jos Malda, Luc J.W. van der Laan, Nynke I. Kramer, Kerstin Schneeberger, Riccardo Levato, Bart Spee*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

5 Citations (Scopus)
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Abstract

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.

Original languageEnglish
Article number2100327
JournalMacromolecular Bioscience
Volume21
Issue number12
Early online date24 Sep 2021
DOIs
Publication statusPublished - Dec 2021

Bibliographical note

Funding Information:
This work is part of the research program Applied and Engineering Sciences with project number 15498, which is financed by the Dutch Research Council (NWO). R.L. acknowledges funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme (grant agreement No. 949806 and No. 964497) and the Gravitation Program “Materials Driven Regeneration”, funded by the Dutch Research Council (NWO), project number 024.003.013.

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

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