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1.发明授权Method for culturing three-dimensional tissue in diffusion gradient bioreactor and use thereof 失效在扩散梯度生物反应器中培养三维组织的方法及其用途公开(公告)号：US06218182B1
公开(公告)日：2001-04-17
申请号：US09470317
申请日：1999-12-21
IPC分类号： A01N102
CPC分类号： C12M29/04 , A61F2/022 , A61M1/3489 , C12M21/08 , C12M25/14 , C12M35/04 , C12M35/08 , C12M41/32 , C12N5/0671 , C12N2500/02 , C12N2500/32
摘要： A tissue engineering bioreactor is disclosed for growing three-dimensional tissue. Cells are seeded onto a mesh and provided with two media flows, each contacting a different side of the cells. The media flows contain different concentrations of nutrients, allowing nutrients to be delivered to the cells by diffusion gradient. The bioreactor can be used to grow liver tissue, and designed as an extracorporeal liver assist device in which blood or plasma is exposed to the three-dimensional liver tissue. The blood or plasma from a patient directed to flow against the liver tissue. The liver tissue is further exposed on its opposite side to media providing nutrients and gases. The device provides porous boundaries between the blood or plasma, tissue, and media; allowing nutrient and protein delivery by diffusion gradient to dialyze a patient's blood.
摘要翻译： 公开了用于生长三维组织的组织工程生物反应器。 将细胞接种到网状物上，并提供两个培养基流，每个接触细胞的不同侧。 培养基流中含有不同浓度的营养物质，允许通过扩散梯度将营养物质递送到细胞。 生物反应器可用于生长肝组织，并被设计为体外肝辅助装置，其中血液或血浆暴露于三维肝组织。 来自患者的血液或血浆导向流向肝组织。 肝脏组织进一步暴露在与提供营养和气体的介质的相对侧。 该装置在血液或血浆，组织和培养基之间提供多孔边界; 允许营养和蛋白质通过扩散梯度递送以透析患者的血液。
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公开(公告)号：US6008049A
公开(公告)日：1999-12-28
申请号：US136503
申请日：1998-08-19
IPC分类号： C12M1/00 , A01N1/02 , A61F2/02 , A61M1/34 , A61M1/36 , C12M1/16 , C12M3/06 , C12N5/00 , C12N5/071 , C12M3/00
CPC分类号： C12M29/04 , A61F2/022 , A61M1/3489 , C12M21/08 , C12M25/14 , C12M35/04 , C12M35/08 , C12M41/32 , C12N5/0671 , C12N2500/02 , C12N2500/32
摘要： A tissue engineering bioreactor is disclosed for growing three-dimensional tissue. Cells are seeded onto a mesh and provided with two media flows, each contacting a different side of the cells. The media flows contain different concentrations of nutrients, allowing nutrients to be delivered to the cells by diffusion gradient. The bioreactor can be used to grow liver tissue, and designed as an extracorporeal liver assist device in which blood or plasma is exposed to the three-dimensional liver tissue. The blood or plasma from a patient directed to flow against the liver tissue. The liver tissue is further exposed on its opposite side to media providing nutrients and gases. The device provides porous boundaries between the blood or plasma, tissue, and media, allowing nutrient and protein delivery by diffusion gradient to dialyze a patient's blood.
摘要翻译： 公开了用于生长三维组织的组织工程生物反应器。 将细胞接种到网状物上，并提供两个培养基流，每个接触细胞的不同侧。 培养基流中含有不同浓度的营养物质，允许通过扩散梯度将营养物质递送到细胞。 生物反应器可用于生长肝组织，并被设计为体外肝辅助装置，其中血液或血浆暴露于三维肝组织。 来自患者的血液或血浆导向流向肝组织。 肝脏组织进一步暴露在与提供营养和气体的介质的相对侧。 该装置在血液或血浆，组织和培养基之间提供多孔边界，允许营养和蛋白质通过扩散梯度递送以透析患者的血液。
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公开(公告)号：US5858721A
公开(公告)日：1999-01-12
申请号：US978520
申请日：1997-11-25
IPC分类号： A61B10/00 , A61B10/02 , A61B19/00 , A61K35/12 , A61K35/28 , A61L27/38 , A61L27/60 , C12N5/00 , C12N5/071 , C12N5/077 , C12N5/0789 , C12P21/02 , C12N5/10
CPC分类号： A61L27/3604 , A61B90/00 , A61K35/28 , A61L27/3886 , A61L27/60 , C12N5/0698 , A61B2010/0258 , A61K2035/124 , A61K35/12 , C12N2500/34 , C12N2501/11 , C12N2501/33 , C12N2501/335 , C12N2501/39 , C12N2502/091 , C12N2502/094 , C12N2502/1323 , C12N2503/04 , C12N2510/00 , C12N2533/30 , C12N2533/40 , C12N2533/70 , Y10S623/915
摘要： The present invention relates to a three-dimensional cell culture system which can be used to culture a variety of different cells and tissues in vitro for prolonged periods of time. In accordance with the invention, cells derived from a desired tissue are inoculated and grown on a pre-established stromal support matrix. The stromal support matrix comprises stromal cells, such as fibroblasts actively growing on a three-dimensional matrix. Stromal cells may also include other cells found in loose connective tissue such as endothelial cells, macrophages/monocytes, adipocytes, pericytes, reticular cells found in bone marrow stroma, etc. The stromal matrix provides the support, growth factors, and regulatory factors necessary to sustain long-term active proliferation of cells in culture. When grown in this three-dimensional system, the proliferating cells mature and segregate properly to form components of adult tissues analogous to counterparts found in vivo.
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公开(公告)号：US5510254A
公开(公告)日：1996-04-23
申请号：US241259
申请日：1994-05-11
IPC分类号： A61B10/00 , A61B10/02 , A61B19/00 , A61K35/12 , A61K35/28 , A61L27/38 , A61L27/60 , C12N5/00 , C12N5/071 , C12N5/077 , C12N5/0789 , C12M3/00
CPC分类号： C12N5/0671 , A61B90/00 , A61K35/28 , A61L27/3604 , A61L27/3629 , A61L27/3637 , A61L27/3641 , A61L27/3804 , A61L27/3839 , A61L27/3886 , A61L27/3895 , A61L27/60 , A61B2010/0258 , A61K2035/124 , A61K35/12 , C12N2500/34 , C12N2501/11 , C12N2501/33 , C12N2501/335 , C12N2501/39 , C12N2502/13 , C12N2503/04 , C12N2510/00 , C12N2533/30 , C12N2533/40 , C12N2533/70
摘要： The present invention relates to a three-dimensional cell and tissue culture system. In particular, it relates to this culture system for the long term culture of liver cells and tissues in vitro in an environment that more closely approximates that found in vivo. The culture system described herein provides for proliferation and appropriate liver cell maturation to form structures analogous to tissue counterparts in vivo. The resulting liver tissues survive for prolonged periods, perform liver-specific functions, and maintain hepatic tissue architecture following in vivo implantation. The liver cultures have a variety of applications ranging from transplantation or implantation in vivo, to screening cytotoxic compounds and pharmaceutical compounds in vitro, to the production of biologically active molecules in "bioreactors" and to the construction of extracorporeal liver assist device.
摘要翻译： 本发明涉及三维细胞和组织培养系统。 特别地，它涉及这种用于在与体内发现更接近的环境中长期培养肝细胞和组织的培养体系。 本文描述的培养系统提供增殖和合适的肝细胞成熟以形成类似于体内组织对应物的结构。 所得肝组织长时间存活，进行肝特异性功能，并在体内植入后维持肝组织结构。 肝脏培养物具有多种应用，从体内移植或植入到体外筛选细胞毒性化合物和药物化合物，在“生物反应器”中生产生物活性分子以及体外肝辅助装置的构建。
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公开(公告)号：US5443950A
公开(公告)日：1995-08-22
申请号：US131361
申请日：1993-10-04
IPC分类号： A61B10/00 , A61B10/02 , A61B19/00 , A61K35/12 , A61K35/28 , A61L27/38 , A61L27/60 , C12N5/00 , C12N5/071 , C12N5/077 , C12N5/0789 , C12N5/08 , C12N5/22 , C12N11/14 , C12N11/00
CPC分类号： A61L27/3604 , A61B90/00 , A61K35/28 , A61L27/3886 , A61L27/60 , C12N5/0698 , A61B2010/0258 , A61K2035/124 , A61K35/12 , C12N2500/34 , C12N2501/11 , C12N2501/33 , C12N2501/335 , C12N2501/39 , C12N2502/091 , C12N2502/094 , C12N2502/1323 , C12N2503/04 , C12N2510/00 , C12N2533/30 , C12N2533/40 , C12N2533/70 , Y10S623/915
摘要： The present invention relates to a three-dimensional cell culture system which can be used to culture a variety of different cells and tissues in vitro for prolonged periods of time. In accordance with the invention, cells derived from a desired tissue are inoculated and grown on a pre-established stromal support matrix. The stromal support matrix comprises stromal cells, such as fibroblasts actively growing on a three-dimensional matrix. Stromal cells may also include other cells found in loose connective tissue such as endothelial cells, macrophages/monocytes, adipocytes, pericytes, reticular cells found in bone marrow stroma, etc. The stromal matrix provides the support, growth factors, and regulatory factors necessary to sustain long-term active proliferation of cells in culture. When grown in this three-dimensional system, the proliferating cells mature and segregate properly to form components of adult tissues analogous to counterparts found in vivo.
摘要翻译： 本发明涉及三维细胞培养系统，其可用于在体外长时间培养各种不同的细胞和组织。 根据本发明，将来自所需组织的细胞接种并在预先建立的基质支持基质上生长。 基质支持基质包括基质细胞，例如在三维基质上积极生长的成纤维细胞。 基质细胞还可以包括在松散结缔组织中发现的其他细胞，例如内皮细胞，巨噬细胞/单核细胞，脂肪细胞，周细胞，骨髓基质中发现的网状细胞等。基质基质提供了支持，生长因子和调节因子 维持文化中细胞的长期积极扩散。 当在该三维体系中生长时，增殖细胞成熟并适当地分离以形成类似于在体内发现的对应物的成体组织的组分。
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公开(公告)号：US4721096A
公开(公告)日：1988-01-26
申请号：US36154
申请日：1987-04-03
CPC分类号： C12N5/0669 , A61K35/28 , A61L27/60 , A61K2035/124 , C12N2500/34 , C12N2501/11 , C12N2501/33 , C12N2501/335 , C12N2501/39 , C12N2502/1323 , C12N2510/00 , C12N2533/30 , C12N2533/40 , C12N2533/70
摘要： According to the present invention there is provided a process for treating a person whose bone marrow has been destroyed or lost its functional ability. The process includes the steps of obtaining bone marrow from a donor, cryropreserving the marrow, replicating the bone marrow cells in vitro, and then infusing the replicated bone marrow cells into a person whose bone marrow has been destroyed or functionally compromised by disease or the treatment of disease. The person receiving the replicated bone marrow infusion may be the donor or another person. There is also disclosed a process for replicating bone marrow in vitro.
摘要翻译： 根据本发明，提供了一种治疗骨髓已被破坏或失去其功能能力的人的方法。 该方法包括以下步骤：从供体获得骨髓，冷冻保存骨髓，体外复制骨髓细胞，然后将复制的骨髓细胞注入骨髓已经被疾病或治疗破坏或功能受损的人 的疾病 接受复制骨髓输注的人可以是供体或另一个人。 还公开了在体外复制骨髓的方法。
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公开(公告)号：US5962325A
公开(公告)日：1999-10-05
申请号：US157306
申请日：1998-09-18
IPC分类号： C12Q1/02 , A61B10/00 , A61B10/02 , A61B19/00 , A61F2/00 , A61F2/04 , A61F2/06 , A61F2/08 , A61K35/12 , A61K35/28 , A61L27/00 , A61L27/38 , A61L27/60 , C12N5/00 , C12N5/071 , C12N5/077 , C12N5/0789 , G01N33/50 , A01N1/02 , A61F2/10
CPC分类号： A61L27/3886 , A61B90/00 , A61K35/28 , A61L27/3604 , A61L27/3629 , A61L27/3637 , A61L27/3641 , A61L27/3804 , A61L27/3839 , A61L27/3852 , A61L27/3895 , A61L27/60 , C12N5/0655 , G01N33/5088 , A61B2010/0258 , A61F2/0063 , A61F2/04 , A61F2/06 , A61F2/08 , A61K2035/124 , A61K35/12 , C12N2500/34 , C12N2501/11 , C12N2501/15 , C12N2501/33 , C12N2501/335 , C12N2501/39 , C12N2503/04 , C12N2510/00 , C12N2533/40 , G01N2500/00
摘要： The present invention relates to a method of stimulating the proliferation and appropriate cell maturation of a variety of different cells and tissues in three-dimensional cultures in vitro using TGF-.beta. in the culture medium. In accordance with the invention, stromal cells, including, but not limited to, chondrocytes, chondrocyte-progenitors, fibroblasts, fibroblast-like cells, umbilical cord cells or bone marrow cells from umbilical cord blood are inoculated and grown on a three-dimensional framework in the presence of TGF-.beta.. Stromal cells may also include other cells found in loose connective tissue such as endothelial cells, macrophages/monocytes, adipocytes, pericytes, reticular cells found in bone marrow stroma, etc. The stromal cells and connective tissue proteins naturally secreted by the stromal cells attach to and substantially envelope the framework composed of a biocompatible non-living material formed into a three-dimensional structure having interstitial spaces bridged by the stromal cells. The living stromal tissue so formed provides the support, growth factors, and regulatory factors necessary to sustain long-term active proliferation of cells in culture and/or cultures implanted in vivo. When grown in this three-dimensional system, the proliferating cells mature and segregate properly to form components of adult tissues analogous to counterparts in vivo.
摘要翻译： 本发明涉及在培养基中使用TGF-β在体外在三维培养物中刺激多种不同细胞和组织的增殖和适当的细胞成熟的方法。 根据本发明，将来自脐带血的软骨细胞，软骨细胞祖细胞，成纤维细胞，成纤维细胞样细胞，脐带细胞或骨髓细胞的基质细胞接种并生长在三维框架上 在TGF-β的存在下。 基质细胞还可以包括在松散结缔组织中发现的其它细胞，例如内皮细胞，巨噬细胞/单核细胞，脂肪细胞，周细胞，在骨髓基质中发现的网状细胞等。基质细胞天然分泌的基质细胞和结缔组织蛋白附着于 并且基本上包围由生物相容性非生物材料构成的框架，所述骨架形成具有由基质细胞桥接的间隙的三维结构。 如此形成的活的基质组织提供了在体内植入的培养和/或培养物中维持细胞的长期活性增殖所必需的支持，生长因子和调节因子。 当在该三维体系中生长时，增殖细胞成熟并适当地分离以形成类似于体内对应物的成体组织的组分。
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公开(公告)号：US5160490A
公开(公告)日：1992-11-03
申请号：US659220
申请日：1991-02-21
IPC分类号： A61B10/00 , A61B10/02 , A61B19/00 , A61K35/12 , A61K35/28 , A61L27/38 , A61L27/60 , C12N5/00 , C12N5/071 , C12N5/077 , C12N5/0789
CPC分类号： C12N5/0698 , A61B90/00 , A61K35/28 , A61L27/38 , A61L27/60 , A61B2010/0258 , A61K2035/124 , A61K35/12 , C12N2500/34 , C12N2501/11 , C12N2501/33 , C12N2501/335 , C12N2501/39 , C12N2502/091 , C12N2502/094 , C12N2502/1323 , C12N2503/04 , C12N2510/00 , C12N2533/30 , C12N2533/40 , C12N2533/70
摘要： The present invention relates to a three-dimensional cell culture system which can be used to culture a variety of different cells and tissues in vitro for prolonged periods of time. In accordance with the invention, cells derived from a desired tissue are inoculated and grown on a pre-established stromal support matrix. The stromal support matrix comprises stromal cells, such as fibroblasts actively growing on a three-dimensional matrix. Stromal cells may also include other cells found in loose connective tissue such as endothelial cells, macrophages/monocytes, adipocytes, pericytes, reticular cells found in bone marrow stroma, etc. The stromal matrix provides the support, growth factors, and regulatory factors necessary to sustain long-term active proliferation of cells in culture. When grown in this three-dimensional system, the proliferating cells mature and segregate properly to form components of adult tissues analogous to counterparts found in vivo.
摘要翻译： 本发明涉及三维细胞培养系统，其可用于在体外长时间培养各种不同的细胞和组织。 根据本发明，将来自所需组织的细胞接种并在预先建立的基质支持基质上生长。 基质支持基质包括基质细胞，例如在三维基质上积极生长的成纤维细胞。 基质细胞还可以包括在松散结缔组织中发现的其他细胞，例如内皮细胞，巨噬细胞/单核细胞，脂肪细胞，周细胞，骨髓基质中发现的网状细胞等。基质基质提供支持，生长因子和调节因子 维持文化中细胞的长期积极扩散。 当在该三维体系中生长时，增殖细胞成熟并适当地分离以形成类似于在体内发现的对应物的成体组织的组分。
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公开(公告)号：US4963489A
公开(公告)日：1990-10-16
申请号：US242096
申请日：1988-09-08
IPC分类号： A61B10/00 , A61B10/02 , A61B19/00 , A61K35/12 , A61L27/38 , A61L27/60 , C12N5/00 , C12N5/071
CPC分类号： C12N5/0698 , A61B90/00 , A61L27/38 , A61L27/60 , C12N5/0062 , C12N5/0669 , C12N5/0671 , C12N5/0677 , A61B2010/0258 , A61K2035/124 , A61K35/12 , C12N2500/34 , C12N2501/11 , C12N2501/33 , C12N2501/335 , C12N2501/39 , C12N2502/094 , C12N2502/1323 , C12N2502/28 , C12N2503/04 , C12N2510/00 , C12N2533/30 , C12N2533/40 , C12N2533/70
摘要： The present invention relates to a three-dimensional cell culture system which can be used to culture a variety of different cells and tissues in vitro for prolonged periods of time. In accordance with the invention, cells derived from a desired tissue are inoculated and grown on a pre-established stromal support matrix. The stromal support matrix comprises stromal cells, such as fibroblasts, grown to subconfluence on a three-dimensional matrix. Stromal cells may also include other cells found in loose connective tissue such as endothelial cells, macrophages/monocytes, adipocytes, pericytes, reticular cells found in bone marrow stroma, etc. The stromal matrix provides the support, growth factors, and regulatory factors necessary to sustain long-term active proliferation of cells in culture. When grown in this three-dimensional system, the proliferating cells mature and segregate properly to form components of adult tissues analogous to counterparts found in vivo.
摘要翻译： 本发明涉及三维细胞培养系统，其可用于在体外长时间培养各种不同的细胞和组织。 根据本发明，将来自所需组织的细胞接种并在预先建立的基质支持基质上生长。 基质支持基质包括基质细胞，例如成纤维细胞，其在三维基质上生长成亚融合。 基质细胞还可以包括在松散结缔组织中发现的其他细胞，例如内皮细胞，巨噬细胞/单核细胞，脂肪细胞，周细胞，骨髓基质中发现的网状细胞等。基质基质提供了支持，生长因子和调节因子 维持文化中细胞的长期积极扩散。 当在该三维体系中生长时，增殖细胞成熟并适当地分离以形成类似于在体内发现的对应物的成体组织的组分。
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10.发明授权
公开(公告)号：US6022743A
公开(公告)日：2000-02-08
申请号：US264513
申请日：1999-03-08
IPC分类号： C12N11/00 , A61B10/00 , A61B10/02 , A61B19/00 , A61F2/00 , A61F2/04 , A61F2/06 , A61F2/08 , A61K35/12 , A61K35/28 , A61L27/00 , A61L27/38 , A61L27/60 , C12N5/00 , C12N5/071 , C12N5/077 , C12N5/0789 , G01N33/50 , C12N5/08 , C12N11/08
CPC分类号： A61L27/3804 , A61B90/00 , A61K35/28 , A61L27/3629 , A61L27/3637 , A61L27/3641 , A61L27/3839 , A61L27/386 , A61L27/3886 , A61L27/60 , C12N5/0062 , C12N5/066 , C12N5/0671 , C12N5/0676 , C12N5/0677 , C12N5/0684 , C12N5/069 , C12N5/0691 , C12N5/0697 , C12N5/0698 , G01N33/5088 , A61B2010/0258 , A61F2/0063 , A61F2/04 , A61F2/06 , A61F2/08 , A61K2035/124 , A61K35/12 , C12N2500/34 , C12N2501/11 , C12N2501/33 , C12N2501/335 , C12N2501/39 , C12N2502/094 , C12N2502/1323 , C12N2502/28 , C12N2503/04 , C12N2510/00 , C12N2533/30 , C12N2533/40 , C12N2533/70 , G01N2500/00
摘要： A stromal cell-based three-dimensional cell culture system is prepared which can be used to culture a variety of different cells and tissues in vitro for prolonged periods of time. The stromal cells and connective tissue proteins naturally secreted by the stromal cells attach to and substantially envelope a framework composed of a biocompatible non-living material formed into a three-dimensional structure having interstitial spaces bridged by the stromal cells. The living stromal tissue so formed provides the support, growth factors, and regulatory factors necessary to sustain long-term active proliferation of cells in culture and/or cultures implanted in vivo. When grown in this three-dimensional system, the proliferating cells mature and segregate properly to form components of adult tissues analogous to counterparts in vivo, which can be utilized in the body as a corrective tissue. For example, and not by way of limitation, the three-dimensional cultures can be used to form tubular tissue structures, like those of the gastrointestinal and genitourinary tracts, as well as blood vessels; tissues for hernia repair and/or tendons and ligaments; etc.
摘要翻译： 制备基质细胞的三维细胞培养系统，其可用于在体外长时间培养各种不同的细胞和组织。 由基质细胞天然分泌的基质细胞和结缔组织蛋白附着到基本上包围由生物相容的非生物材料组成的框架，所述骨架由形成为具有由基质细胞桥接的间隙的三维结构构成。 如此形成的活的基质组织提供了在体内植入的培养和/或培养物中维持细胞的长期活性增殖所必需的支持，生长因子和调节因子。 当在该三维体系中生长时，增殖细胞成熟并且适当地分离以形成类似于体内对应物的成体组织的组分，其可以在身体中用作矫正组织。 例如，而不是限制，三维培养物可用于形成管状组织结构，如胃肠道和泌尿生殖道以及血管; 用于疝修补和/或腱和韧带的组织; 等等
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