Effect of isoliquiritigenin on viability and differentiated functions of human hepatocytes maintained on PEEK-WC–polyurethane membranes

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• 作者：Loredana De Bartolo ; Sabrina Morelli ; Maria Carmela Gallo ; Carla Campana ; Giancarlo Statti ; Maria Rende ; Simona Salerno and Enrico Drioli
• 关键词：Membrane ; Human hepatocyte ; Liver-specific functions ; Biotransformation ; Isoliquiritigenin
• 刊名：Biomaterials
• 出版年：2005
• 期刊代码：7_01429612
• 类别：ms
• 出版时间：2005
• 卷：26
• 期：33
• 页码：6625-6634
• 文件大小：852 K

摘要

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.