title: Effect of isoliquiritigenin on viability and differentiated functions of human hepatocytes maintained on PEEK-WC-polyurethane membranes.
abstract: In this study, we tested the ability of microporous membranes synthesised from a polymeric blend of modified polyetheretherketone (PEEK-WC) and polyurethane (PU) to support long-term maintenance and differentiation of human liver cells. The effect of isoliquiritigenin (ISL), which is a component of liquorice extract, exhibiting growth stimulatory and antiproliferative dose-dependent effect was investigated by comparing cultures treated with ISL with those untreated. To this purpose, flat-sheet membranes were prepared by a blend of PEEK-WC and PU polymers by phase inverse technique. The morphological and physico-chemical properties were characterised, respectively, by scanning electron microscopy and water contact angle measurements. Human hepatocytes cultured on PEEK-WC-PU membranes were constant up to 1 month albumin production and urea synthesis as well as the synthesis of total proteins. The liver-specific functions were expressed at high levels when cells were cultured on membranes with respect to collagen. Also the biotransformation functions were maintained for all culture periods: the ISL elimination rate increased during the culture time and high values were measured up to 22 days. Thereafter, a decrease was observed. ISL stimulated the proliferation of hepatocytes cultured on both substrata but did not affect their liver-specific functions. Hepatocytes cultured on PEEK-WC-PU membranes responded very well to ISL and expressed high levels of P450 cytochrome. These results demonstrated that long-term maintenance of human liver differentiation can be achieved on PEEK-WC-PU membranes. The incubation with ISL at the investigated concentration could stimulate the proliferation of human hepatocytes in biohybrid systems.
authors.affiliation: Institute on Membrane Technology, National Research Council of Italy, ITM-CNR, c/o University of Calabria, via P. Bucci cubo 17/C, 87030 Rende (CS), Italy. l.debartolo@itm.cnr.it
authors.forename: Loredana
authors.initials: L
authors.lastname: De Bartolo
authors.forename: Sabrina
authors.initials: S
authors.lastname: Morelli
authors.forename: Maria Carmela
authors.initials: MC
authors.lastname: Gallo
authors.forename: Carla
authors.initials: C
authors.lastname: Campana
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Statti
authors.forename: Maria
authors.initials: M
authors.lastname: Rende
authors.forename: Simona
authors.initials: S
authors.lastname: Salerno
authors.forename: Enrico
authors.initials: E
authors.lastname: Drioli
mesh_terms: D001577:Benzophenones; D001672:Biocompatible Materials / Q000737:chemistry; D018929:Cell Culture Techniques; D002462:Cell Membrane / Q000378:metabolism; D049109:Cell Proliferation; D002470:Cell Survival; D002478:Cells, Cultured; D002599:Chalcone / Q000031:analogs & derivatives* / Q000737:chemistry; D047188:Chalcones; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000737:chemistry; D022781:Hepatocytes / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D007659:Ketones / Q000737:chemistry*; D008099:Liver / Q000378:metabolism; D008855:Microscopy, Electron, Scanning; D011092:Polyethylene Glycols / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry; D011140:Polyurethanes / Q000737:chemistry*; D013997:Time Factors; D014508:Urea / Q000494:pharmacology
chemical_list: D001577:Benzophenones; D001672:Biocompatible Materials; D047188:Chalcones; D004791:Enzyme Inhibitors; D007659:Ketones; D011108:Polymers; D011140:Polyurethanes; C063834:polyetheretherketone; D011092:Polyethylene Glycols; D002599:Chalcone; D014508:Urea; C040920:isoliquiritigenin