Highly porous polymer matrices as a three-dimensional culture system for hepatocytes

Highly porous polymer matrices as a three-dimensional culture system for hepatocytes
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DOI:
10.1016/s0963-6897(97)00052-3
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发表时间:
1997-09-01
影响因子:
3.3
通讯作者:
Mooney, DJ
Mooney, DJ
中科院分区:
医学4区
文献类型:
--
作者:
Kaufmann, PM;Heimrath, S;Mooney, DJ

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基于肝细胞的疗法(例如,肝细胞移植和体外支持装置)可以提供治疗肝病患者的替代疗法,但是必须开发将这些细胞定位于给定位置同时维持肝脏特异性基因表达的合适方法。在本研究中评价了作为肝细胞培养系统的(L-乳酸)[PLLA]。使用微粒沥滤技术制造海绵,其孔隙率约为95%,平均孔径为180 μ m的肝细胞接种到这些海绵中,粘附并保持存活14天,然而,这些细胞的白蛋白分泌率低,这是肝脏特异性基因表达的指示用胶原包被海绵,更优选地,用胶原凝胶固定PLLA海绵内的细胞,这些数据表明,多孔PLLA海绵可以提供用于肝细胞长期培养的新系统,并且系统的适当设计可以允许移植在这些基质中的肝细胞的肝脏特异性基因表达增强。(C)1997年爱思唯尔科学公司
Hepatocyte-based therapies (e.g., hepatocyte transplantation and extracorporeal support devices) may provide alternative therapies to treat patients with liver disease, but suitable approaches to localize these cells to a given location while maintaining liver-specific gene expression must be developed, The suitability of highly porous three-dimensional sponges fabricated from poly (L-lactic acid) [PLLA] as an hepatocyte culture system was evaluated in this study, Sponges were fabricated utilizing a particulate leaching technique, and were approximately 95% porous, with an average pore diameter of 180 mu m Hepatocytes seeded into these sponges adhered and remained viable for 14 days, However, the secretion rate of albumin from these cells, an indication of liver-specific gene expression, was low (approximately 6 pg/cell/day at day 1), and decreased steadily over the 14 days of the experiment, Coating sponges with collagen, and more preferably, immobilizing cells within the PLLA sponges with a collagen gel, led to enhanced cell survival and albumin secretion at all time points, These data suggest that porous PLLA sponges may provide a novel system for long-term culture of hepatocytes, and proper design of the system may allow the liver-specific gene expression of hepatocytes transplanted in these matrices to be enhanced. (C) 1997 Elsevier Science Inc.