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1. 发明授权

EP1600498B1 SUBSTRATES FOR HIGH-DENSITY CELL ARRAYS AND PREPARATION PROCESSES AND USES THEREOF 有权
标题翻译：用于高密度ZELLA ORDER板，处理衬底制备和使用它的方法
公开(公告)号：EP1600498B1
公开(公告)日：2012-08-15
申请号：EP03703212.5
申请日：2003-02-06
申请人： Cellseed Inc.
发明人： YAMATO, Masayuki , OKANO, Teruo
IPC分类号： G01N33/50
CPC分类号： G01N33/5023 , G01N33/5008 , G01N33/5011 , G01N33/5014
摘要： It is intended to provide a culture board, cell arrays, an automatic injector for chemicals and an assay system which are required in conveniently assaying various chemicals such as drugs and toxins. Use is made of a high-density cell array board characterized in that, on the surface thereof, domains coated with a cell-adhesive polymer are discontinuously, finely and regularly aligned and these domains are surrounded by domains coated with a cell-nonadhesive and hydrophilic polymer which are further continuously surrounded with domains coated with a cell-nonadhesive and strongly hydrophobic material. Using this high-density cell array board and an assay system with the use of the same, the concentration of a drug (for example, an anticancer agent) to be used can be optimized and thus side effects of the drug can be largely lessened. At the same time, the therapeutic achievement of the drug on a disease can be largely improved. Moreover, this is a highly effective technique which is also applicable to development of drugs, environmental assessment and fundamental studies in life science.

2. 发明公开

EP1602383A1 CELL SHEETS FOR ECTOCORNEA FORMATION, METHOD OF PRODUCING THE SAME AND METHOD OF USING THE SAME 有权转让
标题翻译：电池片形成用于生产和使用外角膜和方法
公开(公告)号：EP1602383A1
公开(公告)日：2005-12-07
申请号：EP04708896.8
申请日：2004-02-06
申请人： Cellseed Inc. , Nishida, Kohji
发明人： OKANO, Teruo , NISHIDA, Kohji , YAMATO, Masayuki
IPC分类号： A61L27/38 , C12N5/00 , C12N11/02
CPC分类号： A61L27/3891 , A61L27/3804 , A61L27/3839 , A61L27/3895 , A61L2430/16 , C12N5/0621 , C12N2539/10
摘要： The present invention has as its objective providing acorneal epithelium forming cell sheet that will adhere well to an anterior segment tissue. To attain this objective, a corneal epithelium forming cell sheet is produced by a process comprising the steps of cultivating under specified conditions corneal epithelium forming cells on a cell culture support comprising a substrate having its surface covered with a temperature responsive polymer of which the hydrating force varies in a temperature range of 0-80°C, optionally stratifying the layer of cultured cells, and thereafter,

(1) adjusting the temperature of the culture solution to either above an upper critical dissolution temperature or below a lower critical dissolution temperature,
(2) bringing the cultured corneal epithelium forming cells into close contact with a carrier, and
(3) detaching the sheet together with the carrier under specified conditions.
摘要翻译：本发明具有作为其目的提供acorneal上皮形成thatwill很好地粘附到前眼部组织细胞片。为了达到这个目的，角膜上皮形成细胞片是通过包括培养的步骤中指定的条件下在细胞培养载体，其包括基板角膜上皮形成细胞的方法产生的具有在其表面覆盖有一个温度响应性聚合物的水合力变化的温度范围内的0-80℃，任选地分层的培养细胞的层，此后，（1）调节所述培养液的温度升高到上述的上临界溶解温度的任一者或低于下临界溶解温度，（ 2）使所培养的角膜上皮形成细胞与载体紧密接触，（3）用所述载体在特定条件下一起拆卸片。

3. 发明公开

EP1312669A1 CULTURED EPIDERMAL CELL SHEET, LAMINATED CULTURED SKIN SHEET AND PROCESS FOR PRODUCING THE SAME 有权
标题翻译：培养表皮细胞层层叠培养的皮肤层和方法及其
公开(公告)号：EP1312669A1
公开(公告)日：2003-05-21
申请号：EP01945763.9
申请日：2001-07-02
申请人： Cellseed Inc.
发明人： OKANO, Teruo , YAMATO, Masayuki , UTSUMI, Mika , KUSHIDA, Ai , KONNO, Chie , KIKUCHI, Akihiko
IPC分类号： C12N5/06 , C12N5/08 , A61L27/38
CPC分类号： A61L27/3804 , A61L27/362 , A61L27/60 , C12N5/0698 , C12N2502/094 , C12N2502/1323 , C12N2539/10
摘要： Cells are cultured on a cell culture support having a substrate surface coated with a temperature-responsive polymer whose upper or lower critical solution temperature in water is 0~80°C, optionally forming multiple cultured cell layers by a conventional technique, and subsequently:

(1) the temperature of the culture solution is brought to above the upper critical solution temperature or below the lower critical solution temperature;
(2) the cultured epidermal cell sheet or multi-layered skin sheet is brought into close contact with the polymer membrane; and
(3) the sheet is peeled off together with the polymer membrane. The thus obtained epidermal cultured cell sheet and multi-layered cultured skin sheet do not degrade E-cadherin or laminin 5 as contrasted with Dispase treatment and they still involve very few structural defects; these sheets hence hold great promise in clinical applications such as skin grafting.
摘要翻译：细胞在具有涂覆有温度响应性聚合物，其上或低临界溶解温度在水中是0代字号及80℃下，通过常规技术OPTIONALLY形成多个培养细胞的层，并且随后在基板表面上的细胞培养载体培养的：（ 1）培养液的温度高于上临界溶液温度或低于下临界溶解温度升至; （2）培养的表皮细胞片或多层表层板被带入与该聚合物膜紧密接触; 和（3）片材与聚合物膜一起被剥离。将如此得到的培养表皮细胞片和多层培养皮肤片不降解E-钙粘蛋白或层粘连蛋白5与分散酶处理和护理观照它们涉及非常少的结构缺陷; 论文床单因此保持在临床应用中巨大潜力：如皮肤移植。

4. 发明授权

EP1302535B1 HEART MUSCLE-LIKE CELL SHEET, THREE-DIMENSIONAL CONSTRUCT, HEART MUSCLE-LIKE TISSUE AND PROCESS FOR PRODUCING THE SAME 有权
标题翻译：心肌样细胞层三维构建，心脏肌肉LIKE用于生产织物与方法
公开(公告)号：EP1302535B1
公开(公告)日：2011-01-19
申请号：EP01945762.1
申请日：2001-07-02
申请人： Cellseed Inc.
发明人： OKANO, Teruo , SHIMIZU, Tatsuya , YAMATO, Masayuki , KIKUCHI, Akihiko
IPC分类号： A61L27/38 , C12N5/071
CPC分类号： A61L27/383 , A61K35/12 , A61L27/3826 , A61L27/3839 , C12N5/0657 , C12N2539/10
摘要： A heart muscle cell sheet can be three-dimensionally cultured and a heart muscle-like tissue can be constructed by culturing cells on a cell culture support which comprises a base material coated with a temperature-responsive polymer having an upper or lower critical temperature of dissolution in water of from 0 to 80°C, and then (1) adjusting the temperature of the liquid culture medium to a level higher than the upper critical dissolution temperature or lower than the lower critical dissolution temperature; and, if necessary, (2) closely adhering the cultured cell sheet to a polymer film; and (3) peeling off as such together with the polymer film.

5. 发明公开

EP1859817A1 CULTURED CELL SHEET, PROCESS FOR PRODUCING THE SAME AND METHOD FOR RESTORING TISSUE USING THE SAME 审中-公开
标题翻译： BRED电池板，方法进行恢复组织制备和使用方法的板
公开(公告)号：EP1859817A1
公开(公告)日：2007-11-28
申请号：EP06714891.6
申请日：2006-02-28
申请人： Cellseed Inc.
发明人： KANZAKI, Masato , YAMATO, Masayuki , KOHNO, Tinatsu , SEKINE, Hidekazu , KIKUCHI, Akihiko , OKANO, Teruo , ONUKI, Takamasa
IPC分类号： A61L27/00 , C12N5/06
CPC分类号： A61L27/3895 , A61L27/34 , A61L27/3804 , A61L27/3839 , C12N5/0068 , C12N5/0688 , C12N2533/30
摘要： The problem to be solved by the present invention is to provide a cultured cell sheet having a superior tissue adhesiveness and an excellent flexibility. The problems can be solved by producing the cultured cell sheet in which cells are cultured in the presence of a surfactant protein or a cross-linking inhibitor on a surface of a cell culture support that is coated with a temperature responsive polymer having an upper or lower critical solution temperature ranging from 0°C to 80°C in water, including steps of: adjusting the temperature of the culture medium to a temperature below the lower critical solution temperature or above the upper critical solution temperature; and detaching the cultured cell sheet.
摘要翻译：通过本发明要解决的问题是提供具有优异的密合性的组织和优良的柔软性的培养细胞片。这些问题可以通过产生，其中细胞是在表面活性剂蛋白或细胞培养载体的一个表面上的交联抑制剂的存在下培养并涂覆有在上部或下部的温度响应性聚合物的培养细胞片来解决临界溶液温度下在水中范围从0℃至80℃，包括以下步骤：调节所述培养液的温度至低于最低临界溶解温度或高于该上限临界溶解温度的温度; 和分离培养的细胞片。

6. 发明公开

EP1598417A1 ANTERIOR OCULAR SEGMENT RELATED CELL SHEET, THREE-DIMENSIONAL STRUCTURES AND PROCESS FOR PRODUCING THE SAME 审中-公开
标题翻译： ZELLBLATT DES VORDEREN AUGENSEGMENTS，DREIDIMENSIONALE STRUKTUREN UND HERSTELLUNGSVERFAHRENDAFÜR
公开(公告)号：EP1598417A1
公开(公告)日：2005-11-23
申请号：EP03703213.3
申请日：2003-02-06
申请人： Cellseed Inc.
发明人： YAMATO, Masayuki , OKANO, Teruo
IPC分类号： C12N5/06 , A61F9/007
CPC分类号： C12N5/0621 , A61K35/12
摘要： An anterior ocular segment related cell sheet or three-dimensional structure that have only a few structural defects as they have been recovered retaining the intercellular desmosome structure and the basement membrane-like protein between cell and substrate. The anterior ocular segment related cell sheet or three-dimensional structure is produced by a process comprising the steps of cultivating cells on a cell culture support comprising a substrate having its surface covered with a temperature responsive polymer having an upper or lower critical dissolution temperature of 0-80°C with respect to water, optionally stratifying the layer of cultured cells by the usual method, and thereafter,

(1) adjusting the temperature of the culture solution to either above the upper critical dissolution temperature or below the lower critical dissolution temperature, and further optionally
(2) bringing the cultured anterior ocular segment related cell sheet or three-dimensional structure into close contact with a polymer membrane, and
(3) detaching the sheet or three-dimensional structure together with the polymer membrane.
摘要翻译：前眼部相关的细胞片或三维结构，只有几个结构缺陷，因为它们已经被回收，保留了细胞和基质之间的细胞间质粒结构和基底膜样蛋白。前眼部相关细胞片或三维结构的方法包括以下步骤：在细胞培养支持物上培养细胞，所述细胞培养载体包含其表面被温度响应性聚合物覆盖的基底，所述温度响应性聚合物具有上或下临界溶解温度为0 -80℃，任选地通过常规方法对培养细胞层进行分层，然后（1）将培养溶液的温度调节至高于上临界溶解温度或低于临界溶解温度以下，进一步任选地（2）使培养的眼前段相关细胞片或三维结构与聚合物膜紧密接触，和（3）与聚合物膜一起分离片或三维结构。

7. 发明授权

EP1748064B1 Cultured periodontal ligament cell sheet, process for producing the same and method of use thereof 有权
公开(公告)号：EP1748064B1
公开(公告)日：2019-04-17
申请号：EP05734422.8
申请日：2005-04-25
申请人： CellSeed Inc.
发明人： OKANO, Teruo , HASEGAWA, Masateru , YAMATO, Masayuki , KIKUCHI, Akihiko , ISHIKAWA, Isao
IPC分类号： C12N5/077 , A61C5/00 , A61C8/02 , A61K35/32 , A61P1/02

8. 发明授权

EP1312669B1 CULTURED EPIDERMAL CELL SHEET, LAMINATED CULTURED SKIN SHEET AND PROCESS FOR PRODUCING THE SAME 有权
标题翻译：培养表皮细胞层层叠培养的皮肤层和方法及其
公开(公告)号：EP1312669B1
公开(公告)日：2011-09-14
申请号：EP01945763.9
申请日：2001-07-02
申请人： CellSeed Inc.
发明人： OKANO, Teruo , YAMATO, Masayuki , UTSUMI, Mika , KUSHIDA, Ai , KONNO, Chie , KIKUCHI, Akihiko
IPC分类号： C12N5/07 , C12N5/071
CPC分类号： A61L27/3804 , A61L27/362 , A61L27/60 , C12N5/0698 , C12N2502/094 , C12N2502/1323 , C12N2539/10
摘要： A cultured epidermal cell sheet or a laminated cultured skin sheet is produced by culturing cells on a cell culture support which comprises a base material coated with a temperature-responsive polymer having an upper or lower critical temperature of dissolution in water of from 0 to 80?C, laminating the cultured cell layers if necessary, and then (1) adjusting the temperature of the liquid culture medium to a level higher than the upper critical dissolution temperature or lower than the lower critical dissolution temperature; (2) closely adhering the cultured epidermal cell sheet or the laminated skin sheet to a polymer film; and (3) peeling off as such together with the polymer film. Because of not decomposing E-cadherin or laminin 5 as in the case of treating with dispase and suffering from little structural defects, the cultured epidermal cell sheet and laminated cultured skin sheet thus obtained are strongly expected as being applicable to clinical operations such as skin transplantation.

9. 发明公开

EP1748064A1 CULTURED PERIODONTAL MEMBRANE CELL SHEET, PROCESS FOR PRODUCING THE SAME AND METHOD OF USE THEREOF 审中-公开
标题翻译：培养牙周MEMBRANZELLAGE，方法及其生产，方法及其使用
公开(公告)号：EP1748064A1
公开(公告)日：2007-01-31
申请号：EP05734422.8
申请日：2005-04-25
申请人： Okano, Teruo , Cellseed Inc.
发明人： OKANO, Teruo , HASEGAWA, Masateru , YAMATO, Masayuki , KIKUCHI, Akihiko , ISHIKAWA, Isao
IPC分类号： C12N5/06 , A61C5/08 , A61C5/10 , A61C8/00 , A61K35/32 , A61P1/02
CPC分类号： A61L27/3886 , A61C8/0006 , A61K35/32 , A61L27/3804 , A61L27/3865 , C12N5/066 , C12N2502/097 , C12N2502/1311 , C12N2513/00 , C12N2539/10
摘要： A cultured periodontal ligament cell sheet is produced by a process comprising culturing cells on a cell culture support composed of a base material whose surface is coated with a temperature-responsive polymer having an upper limit or lower limit critical dissolution temperature in water of 0 to 80°C under specified conditions, (1) regulating the temperature of a culture fluid to the upper limit critical dissolution temperature or higher or to the lower limit critical temperature or lower, (2) allowing a cultured periodontal ligament cell sheet resulting from the culturing to adhere to a carrier and (3) detaching the sheet intact together with the carrier. This cultured periodontal ligament cell sheet has a syndesmotic microstructure, exhibits extremely high bioadherence to the dental root surface and realizes high density transplantation of target cells and positive reconstruction of periodontal tissues. Moreover, through lamination of cell sheets to be transplanted and donation of a three-dimensional polarity, highly efficient reconstruction of an adhesion apparatus can be accomplished and clinical application thereof to moderate periodontitis, severe peridontitis, gingival recession and the like is highly promising.
摘要翻译：甲培养的牙周膜细胞片是通过包括培养细胞在基底材料上，其表面涂覆有具有在0至80的水上限或下限临界溶解温度的温度响应性聚合物构成的细胞培养载体上的过程中产生的 ℃，在规定条件下，（1）调节培养液的温度到上限临界溶解温度以上或下限临界温度或更低，（2）允许培养的牙周韧带细胞片从培养到所得附着于载体，（3）与载体一起拆卸片完好无损。本培养的牙周膜细胞片具有韧带联合微观结构表现出非常高的生物粘附到牙齿根面，实现了靶细胞和牙周组织的阳性重建的高密度移植。更完了，通过细胞片层的层压要移植和三维极性的捐款，粘附装置的高效率的重建可以实现和临床应用它们至中度牙周炎，严重牙周炎，牙龈萎缩等是非常有前途。

10. 发明公开

EP1731030A1 METHOD OF CONSTRUCTING ANIMAL HAVING CANCER CELLS TRANSPLANTED THEREINTO 有权转让
标题翻译：方法用于生产动物提供ENTRY接枝癌细胞
公开(公告)号：EP1731030A1
公开(公告)日：2006-12-13
申请号：EP05720067.7
申请日：2005-03-04
申请人： Cellseed Inc.
发明人： OKANO, Teruo , KIKUCHI, Akihiko , YAMATO, Masayuki , MASUDA, Akira
IPC分类号： A01K67/027 , G01N33/15
CPC分类号： A01K67/0271 , A01K2227/105 , A01K2267/0331 , A61K49/0008 , C12N5/0693
摘要： A cell culture support is first prepared that is coated on a surface with a polymer the hydration force of which changes in a temperature range of 0-80°C; cancer cells are then cultivated on the support in a temperature region where the polymer has weak hydration force; thereafter, the culture solution is adjusted to a temperature at which the polymer has a stronger hydration force, whereby the cultured cancer cells are detached; the detached cancer cells are then transplanted to a specified site of an animal on which transplantation is to be performed; this method is an efficient way of cancer cells transplantation.

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