Massive culture of human liver cancer cells in a newly developed radial flow bioreactor system: Ultrafine structure of functionally enhanced hepatocarcinoma cell lines
Massive culture of human liver cancer cells in a newly developed radial flow bioreactor system: Ultrafine structure of functionally enhanced hepatocarcinoma cell lines
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在新开发的径向流生物反应器系统中大规模培养人肝癌细胞：功能增强肝癌细胞系的超细结构
DOI：
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发表时间：
1998
期刊：
影响因子：
--
通讯作者：
H. Ikenaga
中科院分区：
文献类型：
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作者：
M. Kawada;S. Nagamori;H. Aizaki;K. Fukaya;M. Niiya;T. Matsuura;H. Sujino;S. Hasumura;Hitoshi Yashida;S. Mizutani;H. Ikenaga
为了启动临床试验，细胞形态和功能的新开发的人工肝支持系统采用高功能的人肝细胞系，FLC-7，所述径向流生物反应器由垂直延伸的圆柱形基质组成，所述圆柱形基质由多孔玻璃珠微载体组成，液体培养基从所述微载体流过所述圆柱形基质。周边朝向中心轴线，产生氧气和营养物的有益浓度梯度，同时防止过度的剪切应力或废物的积累。三维培养系统支持高密度（1.1 × 108个细胞/ml基质）、大规模培养物（4.4 × 1010个细胞/400 ml生物反应器）和长期活力。扫描和透射电子显微镜（SEM和TEM）显示，在单层系统中培养的细胞被压扁，并与许多细胞质的突起延伸。三维培养的细胞呈球形，表面有微绒毛状突起，类似于体内的肝细胞。细胞以高密度集落牢固地附着在微载体的表面上和孔内。球形细胞与相邻细胞保持紧密接触，而液体培养基的循环自由地流过细胞之间的空间。FLC-7细胞产生白蛋白的速率为6.41 µg/24 h/106个细胞。甲胎蛋白（AFP）的生产下降了近三倍，相比单层培养。结果表明，新的人工肝支持系统（ALSS）提供了一个上级三维培养环境，使细胞在自然功能水平上运行。
SummaryWith a view to initiating clinical trials, cell morphology and function for a newly developed artificial liver support system employing highly functional human liver cell line, FLC-7, cultured in a radial flow bioreactor were compared to cells grown in a conventional monolayer culture.The radial flow bioreactor consists of a vertically extended cylindrical matrix comprised of porous glass bead microcarriers through which liquid medium flows from the periphery in toward the central axis generating a beneficial concentration gradient of oxygen and nutrients, while preventing excessive shear stresses or buildup of waste products. The three-dimensional culture system supports high-density (1.1 × 108 cells/ml-matrix), large scale cultures (4.4 × 1010 cells/400 ml-bioreactor) with long-term viability. Scanning and transmission electron microscopy (SEM and TEM) revealed that cells cultured in a monolayer system were flattened and extended with numerous cytoplasmic projections. Cells in the three-dimensional culture were spherical and covered with microvillilike processes resembling liver cells in vivo. The cells were solidly attached on the surfaces and within the pores of the microcarriers in highly dense colonies. The spherical cells remained in close contact with adjacent cells, while circulation of liquid medium flowed freely through spaces between cells. FLC-7 cells produced albumin at a rate of 6.41 µg/24 h/106 cells. Alpha-fetoprotein (AFP) production dropped nearly threefold in comparison to monolayer cultures. Results demonstrated that the new artificial liver support systems (ALSS) provides a superior three-dimensional culture environment that allows cells to perform at naturally functioning levels.
体外肝脏辅助装置治疗合体巨细胞肝炎一例。
DOI：
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发表时间：
1994
期刊：
The American journal of gastroenterology
影响因子：
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作者：
Sussman,NL;Finegold,MJ;Barish,JP;Kelly,JH
通讯作者：
Kelly,JH
原发性硬化性胆管炎患者肝移植的疗效。
DOI：
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发表时间：
1993
期刊：
Surgery, gynecology & obstetrics
影响因子：
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作者：
Abu-Elmagd,KM;Malinchoc,M;Dickson,ER;Fung,JJ;Murtaugh,PA;Langworthy,AL;Demetris,AJ;Krom,RA;VanThiel,DH;Starzl,TE
通讯作者：
Starzl,TE