title: Cell sources for in vitro human liver cell culture models.
abstract: In vitro liver cell culture models are gaining increasing importance in pharmacological and toxicological research. The source of cells used is critical for the relevance and the predictive value of such models. Primary human hepatocytes (PHH) are currently considered to be the gold standard for hepatic in vitro culture models, since they directly reflect the specific metabolism and functionality of the human liver; however, the scarcity and difficult logistics of PHH have driven researchers to explore alternative cell sources, including liver cell lines and pluripotent stem cells. Liver cell lines generated from hepatomas or by genetic manipulation are widely used due to their good availability, but they are generally altered in certain metabolic functions. For the past few years, adult and pluripotent stem cells have been attracting increasing attention, due their ability to proliferate and to differentiate into hepatocyte-like cells in vitro However, controlling the differentiation of these cells is still a challenge. This review gives an overview of the major human cell sources under investigation for in vitro liver cell culture models, including primary human liver cells, liver cell lines, and stem cells. The promises and challenges of different cell types are discussed with a focus on the complex 2D and 3D culture approaches under investigation for improving liver cell functionality in vitro Finally, the specific application options of individual cell sources in pharmacological research or disease modeling are described.
authors.affiliation: Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Charité - Universitätsmedizin Berlin, 13353 Berlin, Germany katrin.zeilinger@charite.de.
authors.forename: Katrin
authors.initials: K
authors.lastname: Zeilinger
authors.affiliation: Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Charité - Universitätsmedizin Berlin, 13353 Berlin, Germany.
authors.forename: Nora
authors.initials: N
authors.lastname: Freyer
authors.affiliation: Department of General-, Visceral- and Transplantation Surgery, Charité - Universitätsmedizin Berlin, 13353 Berlin, Germany.
authors.forename: Georg
authors.initials: G
authors.lastname: Damm
authors.affiliation: Department of General-, Visceral- and Transplantation Surgery, Charité - Universitätsmedizin Berlin, 13353 Berlin, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Seehofer
authors.affiliation: Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Charité - Universitätsmedizin Berlin, 13353 Berlin, Germany.
authors.forename: Fanny
authors.initials: F
authors.lastname: Knöspel
mesh_terms: D018929:Cell Culture Techniques; D002460:Cell Line; D002478:Cells, Cultured / Q000378:metabolism*; D022781:Hepatocytes / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008099:Liver / Q000166:cytology*; D013234:Stem Cells / Q000378:metabolism
keywords: 3D culture technologies; Liver cell culture; in vitro models; liver cell lines; primary human hepatocytes; stem cells