TY - JOUR
T1 - Bioprinting of Human Liver-Derived Epithelial Organoids for Toxicity Studies
AU - Bouwmeester, Manon C.
AU - Bernal, Paulina N.
AU - Oosterhoff, Loes A.
AU - van Wolferen, Monique E.
AU - Lehmann, Vivian
AU - Vermaas, Monique
AU - Buchholz, Maj Britt
AU - Peiffer, Quentin C.
AU - Malda, Jos
AU - van der Laan, Luc J.W.
AU - Kramer, Nynke I.
AU - Schneeberger, Kerstin
AU - Levato, Riccardo
AU - Spee, Bart
N1 - Publisher Copyright:
© 2021 The Authors. Macromolecular Bioscience published by Wiley-VCH GmbH
PY - 2021/12
Y1 - 2021/12
N2 - 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.
AB - 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.
KW - drug induced liver injury
KW - extrusion-based bioprinting
KW - in vitro modeling
KW - organoids
UR - http://www.scopus.com/inward/record.url?scp=85116316730&partnerID=8YFLogxK
U2 - 10.1002/mabi.202100327
DO - 10.1002/mabi.202100327
M3 - Article
C2 - 34559943
AN - SCOPUS:85116316730
SN - 1616-5187
VL - 21
JO - Macromolecular Bioscience
JF - Macromolecular Bioscience
IS - 12
M1 - 2100327
ER -