Establishing a 3d in vitro hepatic model mimicking physiologically relevant to in vivo state
Kang H.K. Sarsenova M. Kim D.-H. Kim M.S. Lee J.Y. Sung E.-A. Kook M.G. Kim N.G. Choi S.W. Ogay V. Kang K.-S.
May 2021MDPI
Cells
2021#10Issue 5
Three-dimensional (3D) bioprinting is a promising technology to establish a 3D in vitro hepatic model that holds great potential in toxicological evaluation. However, in current hepatic models, the central area suffers from hypoxic conditions, resulting in slow and weak metabolism of drugs and toxins. It remains challenging to predict accurate drug effects in current bioprinted hepatic models. Here, we constructed a hexagonal bioprinted hepatic construct and incorporated a spinning condition with continuous media stimuli. Under spinning conditions, HepG2 cells in the bioprinted hepatic construct exhibited enhanced proliferation capacity and functionality compared to those under static conditions. Additionally, the number of spheroids that play a role in boosting druginduced signals and responses increased in the bioprinted hepatic constructs cultured under spinning conditions. Moreover, HepG2 cells under spinning conditions exhibited intensive TGFβ-induced epithelial-to-mesenchymal transition (EMT) and increased susceptibility to acetaminophen (APAP)induced hepatotoxicity as well as hepatotoxicity prevention by administration of N-acetylcysteine (NAC). Taken together, the results of our study demonstrate that the spinning condition employed during the generation of bioprinted hepatic constructs enables the recapitulation of liver injury and repair phenomena in particular. This simple but effective culture strategy facilitates bioprinted hepatic constructs to improve in vitro modeling for drug effect evaluation.
3D bioprinting , Dynamic environment , In vitro model , Liver
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Adult Stem Cell Research Center, College of Veterinary Medicine, Seoul National University, Seoul, 08826, South Korea
Stem Cell Laboratory, National Center for Biotechnology, 13/5 Qorgalzhin Highway, Nur-Sultan, 010000, Kazakhstan
Department of Medicine, Cardiovascular Research Institute, UCSF, San Francisco, 94143, CA, United States
Department of Cell Biology and Molecular Medicine, Rutgers New Jersey Medical School, Newark, 07103, NJ, United States
Adult Stem Cell Research Center
Stem Cell Laboratory
Department of Medicine
Department of Cell Biology and Molecular Medicine
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