公开(公告)号：EP1181355A4

公开(公告)日：2005-05-04

申请号：EP98909974

申请日：1998-01-09

申请人： YISSUM RES DEV CO

发明人： MITRANI EDUARDO N

IPC分类号： A61F2/02 ,  A61M1/34 ,  C12M3/02 ,  C12M3/04 ,  C12M3/06 ,  C12N5/071 ,  C12N5/06

CPC分类号： C12M25/14 ,  A61M1/3472 ,  A61M1/3489 ,  C12M29/10 ,  C12N5/0671

摘要： A device for performing a biological modification of a fluid, particularly in order to assist or replace the functioning of an organ which normally performs this modification, including a collection of liver micro-organ cultures. The device of the present invention is preferably directly connected to a subject for performing this modification.

公开(公告)号：EP1326968A1

公开(公告)日：2003-07-16

申请号：EP01981506.7

申请日：2001-10-12

申请人： Institute of Materials Research and Engineering ,  The National University of Singapore

发明人： YU, Harry ,  LEONG, Kam, W. ,  CHIA, Ser-Mien

IPC分类号： C12N11/04 ,  C12N11/06 ,  C12N11/16

CPC分类号： C12N5/0062 ,  A61K2035/128 ,  C12N5/0012 ,  C12N5/0671 ,  C12N2533/30 ,  C12N2533/54 ,  C12N2533/72 ,  Y10S514/963 ,  Y10S514/97

摘要： A multi-layered microcapsule has an inner extracellular matrix and an outer shell. The inner extracellular matrix includes a first inner layer of biopolymer and a second intermediate layer of polymer that provides partial immune-protection and holds the first layer in place. The outer shell can form an exoskeleton to provide mechanical stability. Each of the individual layers can be varied to optimize mechanical stability, cell function, and immuno-protection.

公开(公告)号：EP1264879A1

公开(公告)日：2002-12-11

申请号：EP01202221.6

申请日：2001-06-08

申请人： Leadd B.V.

发明人： The designation of the inventor has not yet been filed

IPC分类号： C12N5/06

CPC分类号： C12N5/0677 ,  A61K35/12 ,  C12N5/0671 ,  C12N2502/14 ,  C12N2502/22

摘要： The invention relates to the field of the isolation of a cluster of cells and more in particular to the isolation of islets of Langerhans. The invention provides a method for the isolation of a cluster of cells from an isolated organ wherein said cluster of cells encompasses a network of vascular tissue. Furthermore the invention provides a method for the isolation and in vitro prolongation of a cluster of cells from an isolated organ wherein said cluster of cells encompasses a network of vascular tissue. The invention also provides a method for prolonging the in vitro lifespan of a cluster of cells comprising culturing said cluster of cells in a culturing medium comprising an extracellular matrix component which surrounds said cluster of cells in vivo.

摘要翻译： 本发明涉及隔离细胞簇的领域，更具体地涉及兰格汉斯岛的分离。 本发明提供了用于从分离的器官分离细胞簇的方法，其中所述细胞簇包含血管组织网络。 此外，本发明提供了用于从分离的器官分离和体外延长细胞簇的方法，其中所述细胞簇包含血管组织网络。 本发明还提供了一种用于延长细胞群的体外寿命的方法，包括在培养培养基中培养所述细胞簇，所述培养基包含在体内围绕所述细胞群的细胞外基质组分。

公开(公告)号：EP1123975A4

公开(公告)日：2002-06-19

申请号：EP99973970

申请日：1999-11-10

申请人： BIO QUEST RES LTD

发明人： GOTO MITSUAKI ,  AKAIKE TOSHIHIRO ,  YANG JUN

IPC分类号： C12M3/00 ,  C12N1/38 ,  C12N5/00 ,  C12N5/02 ,  C12N5/071 ,  C12N11/10 ,  C08B37/00 ,  C08B37/06 ,  C12M1/40

CPC分类号： C12N5/0068 ,  C12N5/0671 ,  C12N2501/11 ,  C12N2501/33 ,  C12N2533/70

摘要： Three-dimensional cell incubation media constructed by three-dimensionally shaping cell incubation media comprising sugar chain polymers having at least one type of sugar chain attached thereto as a side chain via a spacer molecule. Preferable examples of the sugar chain polymers include those having carboxyl such as alginic acid, hyaluronic acid, pectic acid and derivatives thereof. Since such a medium has, as the side chain, a sugar chain capable of specifically recognizing certain cells, cells incubated therein undergo a specific interaction with the sugar chain so that the proliferation properties, morphology and functions of the cells can be sustained or improved and a cell morphology similar to the one in vivo can be maintained.

公开(公告)号：EP1203075A1

公开(公告)日：2002-05-08

申请号：EP00943034.9

申请日：2000-06-21

申请人： THE GENERAL HOSPITAL CORPORATION ,  ORGANOGENESIS INC.

发明人： COSMAN, Maury, D. ,  DIMILLA, Paul, A. ,  TONER, Mehmet ,  YARMUSH, Martin, L. ,  BALIS, Ulysses, J. ,  TILLES, Arno, W.

IPC分类号： C12N5/06 ,  C12M3/06

CPC分类号： A61M1/3472 ,  A61F2/022 ,  A61M1/3482 ,  A61M1/3489 ,  A61M1/3633 ,  A61M2210/1071 ,  C12M23/24 ,  C12M29/04 ,  C12M29/10 ,  C12N5/0068 ,  C12N5/0671

摘要： The invention features modular cell culturing devices (1) including one or more flat - plate modules (2), and is based on the discovery that if the flows of liquid medium and oxygenated fluid are separated by a gas-permeable, liquid-impermeable membrane, and the cells are grown attached to the liquid side of the membrane, the device can be used to culture cells with transport of oxygen through the membrane (i.e., direct oxygenation), without regard for the flow rate of the liquid medium passing through the device. The new flow-through cell culturing devices (1) can thus be used to culture cells, e.g., hepatocytes, with high levels of cell function in organ, e.g., liver assist systems, for production of cells, for production of cell-derived products, such as proteins or viruses, or for systems to treat biological liquid to remove toxins, such as ammonia, or add cell-synthesized products, or both.

公开(公告)号：EP1063289A1

公开(公告)日：2000-12-27

申请号：EP99112279.7

申请日：1999-06-25

申请人： JMS Co., Ltd.

发明人： Qiang,Shi Dr. ,  Klinkmann, Horst ,  Kimura, Hajime ,  Kazuo, Izumi

IPC分类号： C12N5/08 ,  A61F2/02 ,  A61M1/36

CPC分类号： C09D11/38 ,  A61F2/022 ,  A61M1/3687 ,  A61M1/3689 ,  C12N5/0671 ,  C12N2501/06 ,  C12N2531/00

摘要： Disclosed is a blood perfusion device or apparatus that is used for bioartificial liver support. Human hepatocyte lines established from normal regenerating liver tissue and modulated in toxin-challenging conditions are provided. These functional hepatocytes exhibit extraordinarily enhanced detoxification functions, which are characterised by the elevated glutathione content and glutathione S-transferase activity. A bioreactor is constructed with the functional hepatocytes for bioartificial liver support system, which includes perfusion inlets and perfusion outlets, a containment vessel, a centrifugal pump and macroporous microcarriers where the functional hepatocytes are grown.

摘要翻译： 公开了一种用于生物人造肝支持的血液灌注装置或装置。 提供从正常再生肝组织建立并在毒素 - 挑战性条件下调节的人肝细胞系。 这些功能性肝细胞表现出非常强大的解毒功能，其特征在于谷胱甘肽含量升高和谷胱甘肽S-转移酶活性。 构建生物反应器用于生物人造肝支持系统的功能性肝细胞，其包括灌注入口和灌注出口，容纳容器，离心泵和功能性肝细胞生长的大孔微载体。

公开(公告)号：EP1045024A1

公开(公告)日：2000-10-18

申请号：EP99201134.6

申请日：1999-04-12

申请人： K.U. Leuven Research & Development

发明人： The designation of the inventor has not yet been filed

IPC分类号： C12N5/06 ,  C12M3/06 ,  A61K35/407 ,  A61L27/00

CPC分类号： A61L27/3804 ,  A61K35/12 ,  A61L27/3839 ,  C12N5/0068 ,  C12N5/0671 ,  C12N2503/00 ,  C12N2510/04 ,  C12N2533/90

摘要： The present invention relates to a cell line of human immortalized hepatocytes for medical use. In particular, the invention relates to a cell line of human immortalized hepatocytes for the treatment of liver failure. More specifically, the invention relates to a cell line of human hepatocytes for use in a bioartificial liver system for the treatment of chronic or acute liver failure. The invention further relates to the use of said cell line for the preparation of a bioartificial liver system for the treatment of liver failure.
Furthermore, the invention relates to a bioartificial liver system provided with said cell line, and the use thereof for the treatment liver failure.
According to the present invention it has for the first time been demonstrated that a cell line of human immortalized hepatocytes can effectively be used for the treatment of liver failure, resulting in a prolongation of survival accompanied by an improvement of biochemical parameters and neurological status.

摘要翻译： 本发明涉及一种用于医疗用途的人类肝细胞的永生化的细胞系。 特别地，本发明涉及永生化的人类肝细胞的肝衰竭的治疗的细胞系。 更具体地，本发明涉及一种用于在生物人工肝系统中使用用于慢性或急性肝衰竭的治疗的人肝细胞的细胞系。 本发明还涉及到使用所述细胞系用于制备生物人工肝系统的肝功能衰竭的治疗。 进一步，本发明涉及一种设置有所述细胞系生物人工肝系统，以及使用它们用于治疗肝功能衰竭。 。根据本发明，已经在第一次被实例阐述那样人永生化肝细胞的细胞系可以有效地用于肝功能衰竭的治疗，伴有关于提高生化参数和神经状态的存活延长所得到的。

公开(公告)号：EP0953633A1

公开(公告)日：1999-11-03

申请号：EP99303337.2

申请日：1999-04-28

申请人： Livercell L.L.C.

发明人： Curcio, Francesco ,  Coon, Hayden G. ,  Ambesi-Impiombato, Francesco Saverio

IPC分类号： C12N5/06 ,  C12N5/02 ,  C12N5/10 ,  A61K39/12 ,  A61K39/002 ,  A61K47/38 ,  A61K47/42

CPC分类号： C12N5/0671 ,  A61K2035/128 ,  C12N7/00 ,  C12N2503/02 ,  C12N2510/00

摘要： The present invention provides improvements in a method for producing an expanded non-transformed cell culture of human liver cells comprising the steps of: (1) preparing partially purified, minced human liver tissue, (2) concentrating the resulting cells and tissue pieces, (3) resuspending the concentrated tissue cells and pieces in a growth medium, (4) culturing the resuspended cells in the growth medium for a time and under conditions to effect sustained cell division, and (5) passaging the cultured human liver cells periodically to expand the culture. The growth medium comprises a combination of a basal medium and ingredients to provide a medium in which the cultured human liver cells are selectively proliferated without being transformed, providing an expanded culture of proliferated, functionally differentiated human liver cells that is substantially free of fibroblast, macrophage and capillary endothelial cells, the improvement comprising the steps of harvesting cells of the expanded culture at a selected PDL preferably > 5, providing a high density cell suspension of such proliferated human liver cells, and incubating such high density cell suspension in a calm-down medium to induce a mitotically quiescent state and, using a culture procedure which encourages aggregation, making the cells adhere tightly to form a three-dimensional cell organisation typical of the organ of origin, thereby forming organoids. Methods of gel-embedding the single cells, aggregates and organoids produced by the method; the growth medium and calm-down medium; various different methods for use of the normal, proliferated human liver cells produced by the method, are also provided.

摘要翻译： 本发明提供的方法中的改进，在人肝细胞，包括以下步骤的扩展的非转化的细胞培养物中产生：（1）制备部分纯化的，切碎的人肝组织中，（2）浓缩所得的细胞和组织片（ 3）重悬浓缩组织细胞和碎片在生长培养基中，（4）培养所述重新悬浮的细胞在一段时间的生长培养基和条件，以实现持续细胞分裂下，和（5）良好的耐老化培养的人肝细胞定期扩大 文化。 生长培养基包含基础培养基和成分的组合，以提供在其中培养的人肝细胞被选择性而不被转化增殖的培养基中，提供到扩展培养的增殖，功能分化的人肝细胞所做的是基本上不含成纤维细胞，巨噬细胞 和毛细血管内皮细胞，其改进包括所述膨胀培养收获的细胞的步骤中的一个选定的PDL优选> 5，提供的求增殖的人肝细胞中的高密度的细胞悬浮液，并温育寻求在平静的减少具有高密度的细胞悬液 介质以诱导有丝分裂静止状态，并使用鼓励聚合，使细胞附着紧紧以形成三维细胞组织典型来源的器官的培养过程，从而形成类器官。 的方法凝胶嵌入单电池，聚集体和类器官的方法产生; 生长培养基和平静向下介质; 各种不同的方法中使用的正常的，增殖的人肝由该方法产生的细胞，提供了的。

公开(公告)号：EP0725816A1

公开(公告)日：1996-08-14

申请号：EP94930220.0

申请日：1994-10-25

申请人： BADER, Augustinus

发明人： BADER, Augustinus

IPC分类号： C12N5

CPC分类号： C12N5/0671 ,  C12N5/0068 ,  C12N2533/54

摘要： A method of adding extracellular matrix components to the stationary phase of the matrix for bipolar adhesion of hepatocytes enables these substances to be concentrated and bonded to a defined base matrix composed of a simple base matrix (e.g. type I collagen). One advantage, for example when fibronectin is added, is to provide a completely serum-free culture of liver cells while maintaining normal morphology and function; as a result conventional culture media previously unsuited to serum-free culture of liver cells are now also suitable for relatively long-term serum-free culture. Furthermore, reproducibility of trial results and mechanical stability are substantially improved over the conventional form of matrix layering. The method is applied using a specially adapted kit. Other matrix components can also be added to the matrix by this method, and thus concentration and bonding can be effected within the fibrillary matrix skeleton after the base matrix has gelled.

公开(公告)号：EP0673433A1

公开(公告)日：1995-09-27

申请号：EP94900612.0

申请日：1993-11-12

申请人： MERCK & CO. INC.

发明人： HOCHMAN, Jerome ,  LECLUYSE, Edward

IPC分类号： C12Q1 ,  C12N5 ,  G01N33

CPC分类号： G01N33/5008 ,  C12N5/0671 ,  C12N2503/04 ,  C12N2533/54 ,  G01N2500/00

摘要： A method for screening a chemical compound for hepatotoxicity or choleostatic potential, hepatic extraction potential, hepatic discharge into the bile, metabolite production, or the ability to alter hepatic cell metabolism, using a primary hepatic cell culture with a functional bile canalicular network, is disclosed.