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可生物降解和合成膜在大鼠胚胎肝细胞的扩增和功能分化中的应用。

Biodegradable and synthetic membranes for the expansion and functional differentiation of rat embryonic liver cells.

机构信息

Institute on Membrane Technology, ITM-CNR, University of Calabria, Rende, CS, Italy.

出版信息

Acta Biomater. 2011 Jan;7(1):171-9. doi: 10.1016/j.actbio.2010.07.039. Epub 2010 Aug 4.

Abstract

The insufficient availability of donor organs for orthotopic liver transplantation worldwide has urgently increased the requirement for new therapies for acute and chronic liver disease. The creation of an unlimited source of donor cells for hepatocyte transplantation therapy and pharmaceutical applications may be the isolation and expansion of liver progenitor cells or stem cells. Here we report the expansion and functional differentiation of rat embryonic liver cells on biodegradable and synthetic polymeric membranes in comparison with traditional substrates, such as collagen and polystyrene culture dishes. Membranes prepared from chitosan and modified polyetheretherketone were used for the culture of liver progenitor cells derived from rat embryonic liver. Cells proliferated, with a significant increase in their number within 8-11 days. The cells displayed functional differentiation showing urea synthesis, albumin production and diazepam biotransformation on all substrates investigated. In particular, on a chitosan membrane liver-specific functions were expressed at significantly higher levels for prolonged times compared with other synthetic membranes, utilizing traditional substrates (collagen and PSCD) as references. These results demonstrate that chitosan membranes offer cells favourable conditions to promote the expansion and functional differentiation of embryonic liver cells that could be effectively used in liver tissue engineering and in pharmaceutical applications.

摘要

全球用于原位肝移植的供体器官不足,这迫切需要新的疗法来治疗急性和慢性肝病。为肝实质细胞移植治疗和药物应用创造无限的供体细胞来源,可能需要分离和扩增肝祖细胞或干细胞。在这里,我们报告了在生物可降解和合成聚合物膜上培养大鼠胚胎肝细胞的扩增和功能分化,并与传统基质(如胶原和聚苯乙烯培养皿)进行了比较。壳聚糖和改性聚醚醚酮制备的膜用于培养大鼠胚胎肝来源的肝祖细胞。细胞增殖,在 8-11 天内数量显著增加。细胞表现出功能分化,在所有研究的基质上均显示出尿素合成、白蛋白产生和地西泮生物转化。特别是,壳聚糖膜上的肝特异性功能在与其他合成膜相比时,在较长时间内以显著更高的水平表达,利用传统基质(胶原和 PSCD)作为参考。这些结果表明壳聚糖膜为细胞提供了有利的条件,可促进胚胎肝细胞的扩增和功能分化,可有效用于肝组织工程和药物应用。

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