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US5981211A Maintaining cells for an extended time by entrapment in a contracted matrix 失效
标题翻译：通过在收缩的矩阵中捕获来维持细胞长时间
公开(公告)号：US5981211A
公开(公告)日：1999-11-09
申请号：US726652
申请日：1996-10-07
申请人： Wei-Shou Hu , Frank Bernard Cerra , Scott Lyle Nyberg , Matthew Thomas Scholz , Russell A. Shatford
发明人： Wei-Shou Hu , Frank Bernard Cerra , Scott Lyle Nyberg , Matthew Thomas Scholz , Russell A. Shatford
IPC分类号： A61F2/02 , A61K35/12 , A61M1/16 , A61M1/34 , C12M3/06 , C12N5/071 , C12P1/00 , C12M3/00 , C12N5/00 , C12N11/04
CPC分类号： C12N5/0671 , A61F2/022 , A61M1/1625 , A61M1/3475 , A61M1/3489 , C12M21/08 , C12M23/34 , C12M25/12 , C12M25/14 , C12M29/10 , C12M29/16 , A61K2035/126 , C12N2500/02 , C12N2500/90 , C12N2510/00 , C12N2533/30 , C12N2533/54 , Y10S435/813
摘要： Methods of maintaining animal cells for product production, for supporting hepatocyte function and viability to treat a patient suffering from hepatic failure and for preserving tissue-specific function of mammalian cells are carried out with a bioreactor containing a feed and waste chamber and a cell chamber separated by a selectively permeable membrane. Within the cell chamber, a biocompatible contracted three-dimensional gel matrix entraps animal cells or genetic modifications thereof, and a liquid phase contains a concentrated solution of the cell product. The bioreactor uses only two chambers to achieve three distinct zones within the bioreactor. The bioreactor can be of either hollow fiber or flat-bed configuration. In the configuration using hollow fibers, the two fluid paths correspond to the cavity surrounding the hollow fibers (the extracapillary space), and to the lumens of the hollow fibers themselves. Both fluid paths have inlet and outlet ports. Communication between the two fluid paths is across the permeable medium--the hollow fiber material. To prepare a bioartificial liver, hepatocytes are inoculated into the hollow fibers in a solution which quickly forms a highly porous gel. The gel subsequently contracts, leaving an open channel within the hollow fiber adjacent to the gel core entrapped hepatocytes. This channel can be perfused with nutrient media for hepatocytes. The channel can also serve as a waste stream to remove toxins that the hepatocytes have modified to a water soluble form.
摘要翻译：维持用于产品生产的动物细胞，用于支持肝细胞功能和用于治疗患有肝衰竭的患者和维持哺乳动物细胞的组织特异性功能的活性的方法是用含有饲料和废物室的细胞室和分离的细胞室进行的通过选择性渗透膜。在细胞室内，生物相容的收缩的三维凝胶基质包裹动物细胞或其遗传修饰，液相含有细胞产物的浓缩溶液。生物反应器仅使用两个室来实现生物反应器内的三个不同区域。生物反应器可以是中空纤维或平床构型。在使用中空纤维的构造中，两个流体路径对应于围绕中空纤维（毛细管外空间）的空腔以及中空纤维本身的内腔。两个流体路径都具有入口和出口。两个流体路径之间的通信是穿过可渗透介质 - 中空纤维材料。为了制备生物人造肝，将肝细胞以快速形成高度多孔凝胶的溶液接种到中空纤维中。凝胶随后收缩，在中空纤维中留下与凝胶芯捕获的肝细胞相邻的开放通道。该通道可以用肝细胞的营养培养基灌注。该通道还可用作废物流以除去肝细胞已经修饰成水溶性形式的毒素。

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