公开(公告)号：US5962325A

公开(公告)日：1999-10-05

申请号：US157306

申请日：1998-09-18

申请人： Gail K. Naughton ,  Brian A. Naughton

发明人： Gail K. Naughton ,  Brian A. Naughton

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。

公开(公告)号：US5830708A

公开(公告)日：1998-11-03

申请号：US470101

申请日：1995-06-06

申请人： Gail K. Naughton

发明人： Gail K. Naughton

IPC分类号： A61L27/00 ,  A61F2/00 ,  A61F2/10 ,  A61L27/36 ,  A61L31/00 ,  C12N5/00 ,  A61K38/16 ,  C12P21/04

CPC分类号： A61L27/3839 ,  A61L27/3633 ,  A61L27/3683 ,  A61L27/3804 ,  A61F2/0059 ,  A61F2/105

摘要： The present invention is directed to methods for producing naturally secreted human extracellular matrix material and compositions containing the extracellular matrix material. The method includes culturing extracellular matrix-secreting human stromal cells on a biocompatible three-dimensional framework in vitro. After secretion of the extracellular matrix onto the framework, the stromal cells are killed and the cells and cellular contents are removed from the framework. The extracellular matrix material deposited on the framework is collected and further processed to obtain a physiologically acceptable compositions. The compositions of the present invention are useful for the repair of soft tissue and skin defects, including wrinkles and scars.

摘要翻译： 本发明涉及用于产生天然分泌的人细胞外基质材料和含有细胞外基质材料的组合物的方法。 该方法包括在体外在生物相容的三维框架上培养细胞外基质分泌的人类基质细胞。 在细胞外基质分泌到骨架上之后，基质细胞被杀死，细胞和细胞内容物从框架中除去。 收集沉积在骨架上的细胞外基质材料并进一步处理以获得生理上可接受的组合物。 本发明的组合物可用于修复软组织和皮肤缺陷，包括皱纹和疤痕。

公开(公告)号：US5792603A

公开(公告)日：1998-08-11

申请号：US672697

申请日：1996-06-27

申请人： Noushin Dunkelman ,  Alvin E. Peterson ,  Lee Kevin Landeen ,  Joan Zeltinger

发明人： Noushin Dunkelman ,  Alvin E. Peterson ,  Lee Kevin Landeen ,  Joan Zeltinger

IPC分类号： C12M3/00 ,  A61F2/06 ,  A61L2/24 ,  A61L27/50 ,  C12N5/06 ,  C12N5/08

CPC分类号： A61L2/24 ,  A61F2/062 ,  A61L27/507 ,  C12M21/08 ,  C12M23/46 ,  C12M25/14 ,  C12M29/10 ,  C12M35/04 ,  C12M41/00 ,  Y10S623/912

摘要： An apparatus and method for sterilizing, seeding, culturing, storing, shipping, and testing vascular grafts is disclosed. Specifically, the present invention relates to an apparatus and method for seeding and culturing vascular grafts with human cells. The apparatus includes a fluid reservoir, a pump, an alternating pressure source, and at least one treatment chamber. By alternating pressure to a support structure within the treatment chamber upon which a vascular graft scaffold is positioned, a varying radial stress is placed on the scaffold. In an alternative embodiment, fluid is pumped directly through the vascular graft subjecting the vascular graft to radial and shear stresses. Applying shear and/or radial stresses to the vascular graft during seeding and culturing simulates physiological conditions.

摘要翻译： 公开了一种消毒，播种，培养，储存，运输和测试血管移植物的装置和方法。 具体地说，本发明涉及一种用人细胞种植和培养血管移植物的装置和方法。 该装置包括流体储存器，泵，交流压力源和至少一个处理室。 通过交替压力到位于血管移植支架的治疗室内的支撑结构，将变化的径向应力放置在支架上。 在替代实施例中，流体被直接泵送通过血管移植物使血管移植物受到径向和剪切应力。 在播种和培养期间对血管移植物施加剪切和/或径向应力模拟生理条件。

公开(公告)号：US20040219134A1

公开(公告)日：2004-11-04

申请号：US10851938

申请日：2004-05-21

申请人： Advanced Tissue Sciences, Inc.

发明人： Gail K. Naughton ,  Jonathan Noel Mansbridge ,  Robert Emmett Pinney ,  Joan Zeltinger

IPC分类号： A01N063/00

CPC分类号： A61L27/3886 ,  A61L27/3804 ,  A61L27/3839 ,  A61L27/507

摘要： The present invention relates to a method for promoting blood vessel formation in tissues and organs. In particular, the method relates to implantation or attachment of an engineered three-dimensional stromal tissue to promote endothelialization and angiogenesis in the heart and related tissues. The three-dimensional stromal tissue of the present invention may be used in a variety of applications including, but not limited to, promoting repair of and regeneration of damaged cardiac muscle, promoting vascularization and healing during cardiac surgery, promoting blood vessel formation at anastomosis sites, and promoting vascularization and repair of damaged skeletal muscle, smooth muscle or connective tissue.

摘要翻译： 本发明涉及促进组织器官中血管形成的方法。 特别地，该方法涉及植入或附着工程化的三维基质组织以促进心脏和相关组织中的内皮细胞化和血管发生。 本发明的三维基质组织可用于多种应用，包括但不限于促进损伤的心肌的修复和再生，促进心脏手术期间的血管化和愈合，促进吻合部位的血管形成 并促进损伤的骨骼肌，平滑肌或结缔组织的血管化和修复。

公开(公告)号：US6121042A

公开(公告)日：2000-09-19

申请号：US1609

申请日：1997-12-31

申请人： Alvin Peterson ,  Lee K. Landeen ,  John Bennett ,  Jason Gee ,  Scott Chesla ,  Joan Zeltinger ,  James H. Flatt ,  Mark A. Applegate ,  Noushin Dunkelman ,  Stephen V. Kemmerrer

发明人： Alvin Peterson ,  Lee K. Landeen ,  John Bennett ,  Jason Gee ,  Scott Chesla ,  Joan Zeltinger ,  James H. Flatt ,  Mark A. Applegate ,  Noushin Dunkelman ,  Stephen V. Kemmerrer

IPC分类号： C12M3/00 ,  A61F2/08 ,  A61F2/28 ,  C12M3/02 ,  C12N5/00 ,  C12N5/06

CPC分类号： C12M35/04 ,  C12M41/00 ,  A61F2/30756

摘要： An apparatus and method for sterilizing, seeding, culturing, storing, shipping, and testing three-dimensional tissue constructs is disclosed. The apparatus includes a fluid reservoir, a pump, at least one treatment chamber, and a means for controlling media flow characteristics around a tissue construct disposed within the treatment chamber, and for controlling movement of the construct itself, so as to simulate a variety of physiologic conditions. One exemplary embodiment of the invention includes a means for applying an axial stress to the construct. Applying an axial stress to the construct during seeding and culturing results in a tissue-engineered construct with cells and their fibers oriented in a manner which is more likely to possess long term dimensional stability and the patency of native vessels with normal physiologic function.

摘要翻译： 公开了用于灭菌，播种，培养，储存，运送和测试三维组织结构的装置和方法。 该装置包括流体储存器，泵，至少一个处理室，以及用于控制设置在处理室内的组织结构周围的介质流动特性的装置，并且用于控制构造体本身的移动，以便模拟各种 生理条件。 本发明的一个示例性实施例包括用于向结构施加轴向应力的装置。 在播种和培养过程中对构建体施加轴向应力导致组织工程构建体中细胞及其纤维以更可能具有长期尺寸稳定性和具有正常生理功能的天然血管通畅的方式取向。

公开(公告)号：US6060306A

公开(公告)日：2000-05-09

申请号：US912948

申请日：1997-08-14

申请人： James H. Flatt ,  Mark A. Applegate ,  Alvin Peterson

发明人： James H. Flatt ,  Mark A. Applegate ,  Alvin Peterson

IPC分类号： A61F2/00 ,  A61F2/02 ,  A61F2/30 ,  A61F2/46 ,  A61L27/38 ,  C12M3/00 ,  C12N5/00

CPC分类号： C12M23/34 ,  A61F2/0095 ,  A61F2/30756 ,  A61F2/468 ,  A61L27/38 ,  C12M21/08 ,  C12M25/14 ,  C12M41/40 ,  C12M41/44 ,  A61F2002/30062 ,  A61F2002/30762 ,  A61F2210/0004

摘要： An apparatus and method for sterilizing, seeding, culturing, storing, shipping, and testing cartilage constructs is disclosed. The apparatus generally includes a treatment chamber and a means for varying the fluid flow and pressure within the treatment chamber during seeding and culturing. The application of pressure to the cartilage construct improves both the uniformity of seeding throughout the construct and facilitates the flow of nutrients to and removal of waste products from cells embedded in the construct. In this manner, a tissue-engineered cartilage construct with cells and their fibers oriented in a manner which is more likely to possess long term dimensional stability and the patency of cartilage with normal physiologic function may be formed.

摘要翻译： 公开了用于消毒，播种，培养，储存，运送和测试软骨构建体的装置和方法。 该设备通常包括处理室和用于在播种和培养期间改变处理室内的流体流动和压力的装置。 对软骨构造施加压力可改善整个构建体的接种的均匀性，并促进营养物质流入和从植物体内嵌入的细胞中除去废物。 以这种方式，可以形成具有以更可能具有长期尺寸稳定性和具有正常生理功能的软骨通畅的方式取向的细胞及其纤维的组织工程化软骨构建体。

公开(公告)号：US6022743A

公开(公告)日：2000-02-08

申请号：US264513

申请日：1999-03-08

申请人： Gail K. Naughton ,  Brian A. Naughton

发明人： Gail K. Naughton ,  Brian A. Naughton

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

公开(公告)号：US5849588A

公开(公告)日：1998-12-15

申请号：US690955

申请日：1996-08-01

申请人： Brian A. Naughton ,  Gail K. Naughton

发明人： Brian A. Naughton ,  Gail K. Naughton

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 ,  A61K2/00

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。

公开(公告)号：US2512375A

公开(公告)日：1950-06-20

申请号：US67269746

申请日：1946-05-27

申请人： PARFENTJEV IVAN A

发明人： PARFENTJEV IVAN A

IPC分类号： A23K1/10

CPC分类号： A23K10/22

公开(公告)号：US6140039A

公开(公告)日：2000-10-31

申请号：US237980

申请日：1999-01-25

申请人： Gail K. Naughton ,  Brian A. Naughton

发明人： Gail K. Naughton ,  Brian A. Naughton

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 ,  C12N11/08 ,  C12N5/08 ,  C12N11/10

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 provided which can be used to culture a variety of different cells and tissues in vitro for prolonged periods of time. The stromal cells along with 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. Living stromal tissue so formed provides 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. 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. A three-dimensional filamentous tissue having tendon or ligament function is prepared containing fibroblasts and collagen naturally secreted by the fibroblasts attached to and substantially enveloping a three-dimensional filamentous framework.

摘要翻译： 提供了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。 基质细胞以及由基质细胞天然分泌的结缔组织蛋白质附着在基底上并且基本上包围由生物相容的非生物材料组成的框架，所述框架形成为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支持，生长因子和调节因子，以维持体内植入的培养和/或培养物中细胞的长期活性增殖。 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。 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。 制备具有肌腱或韧带功能的三维丝状组织，其含有成纤维细胞和成胶原蛋白天然分泌的胶原，并且基本上包围三维丝状骨架。