In vitro modeling of liver fibrosis with 3D co-culture system using a novel human hepatic stellate cell line

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In vitro modeling of liver fibrosis with 3D co-culture system using a novel human hepatic stellate cell line
Ho-Joon Lee; Seon Ju Mun; Cho-Rok JungHyun Mi Kang; Jae Eun Kwon; Jae Sung Ryu; Hyo Suk Ahn; Ok Seon KwonJiwon Ahn; K S Moon; Myung Jin SonKyung-Sook Chung
Bibliographic Citation
Biotechnology and Bioengineering, vol. 120, no. 5, pp. 1241-1253
Publication Year
Hepatic stellate cells (HSCs) play an important role in liver fibrosis; however, owing to the heterogeneity and limited supply of primary HSCs, the development of in vitro liver fibrosis models has been impeded. In this study, we established and characterized a novel human HSC line (LSC-1), and applied it to various types of three-dimensional (3D) co-culture systems with differentiated HepaRG cells. Furthermore, we compared LSC-1 with a commercially available HSC line on conventional monolayer culture. LSC-1 exhibited an overall upregulation of the expression of fibrogenic genes along with increased levels of matrix and adhesion proteins, suggesting a myofibroblast-like or transdifferentiated state. However, activated states reverted to a quiescent-like phenotype when cultured in different 3D culture formats with a relatively soft microenvironment. Additionally, LSC-1 exerted an overall positive effect on co-cultured differentiated HepaRG, which significantly increased hepatic functionality upon long-term cultivation compared with that achieved with other HSC line. In 3D spheroid culture, LSC-1 exhibited enhanced responsiveness to transforming growth factor beta 1 exposure that is caused by a different matrix-related protein expression mechanism. Therefore, the LSC-1 line developed in this study provides a reliable candidate model that can be used to address unmet needs, such as development of antifibrotic therapies.
Disease modelingFibrosisHepatic stellate cells (HSCs)LiverSpheroidThree?dimensional culture
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Division of Research on National Challenges > Stem Cell Convergenece Research Center > 1. Journal Articles
Division of Research on National Challenges > 1. Journal Articles
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