公开(公告)号：US5853717A

公开(公告)日：1998-12-29

申请号：US447356

申请日：1995-05-23

申请人： Malcolm Schinstine ,  Molly S. Shoichet ,  Frank T. Gentile ,  Joseph P. Hammang ,  Laura M. Holland ,  Brian M. Cain ,  Edward J. Doherty ,  Shelley R. Winn ,  Patrick Aebischer

发明人： Malcolm Schinstine ,  Molly S. Shoichet ,  Frank T. Gentile ,  Joseph P. Hammang ,  Laura M. Holland ,  Brian M. Cain ,  Edward J. Doherty ,  Shelley R. Winn ,  Patrick Aebischer

IPC分类号： A01K67/027 ,  A61K48/00 ,  A61L27/00 ,  A61L27/18 ,  A61L27/22 ,  A61L27/38 ,  C07K14/82 ,  C12N5/00 ,  C12N5/10 ,  C12N15/09 ,  C12N15/12 ,  A01N63/00

CPC分类号： C12N5/0068 ,  A61L27/18 ,  A61L27/227 ,  A61L27/383 ,  A61L27/3834 ,  A61L27/3839 ,  A61L27/3895 ,  C07K14/82 ,  A61K48/00 ,  C12N2510/00 ,  C12N2510/04 ,  C12N2533/30 ,  C12N2533/54 ,  C12N2533/74

摘要： This invention relates to methods and compositions of controlling cell distribution within a bioartificial organ by exposing the cells to a treatment that inhibits cell proliferation, promotes cell differentiation, or affects cell attachment to a growth surface within the bioartificial organ. Such treatments include (1) genetically manipulating cells, (2) exposing the cells to a proliferation-inhibiting compound or a differentiation-inducing compound or removing the cells from exposure to a proliferation-stimulating compound or a differentiation-inhibiting compound; exposing the cells to irradiation, and (3) modifying a growth surface of the BAO with ECM molecules, molecules affecting cell proliferation or adhesion, or an inert scaffold, or a combination thereof. These treatments may be used in combination.

公开(公告)号：US5955095A

公开(公告)日：1999-09-21

申请号：US436281

申请日：1995-08-14

申请人： Frank T. Gentile ,  Tyrone Hazlett ,  Patrick A. Tresco ,  Thomas Flanagan ,  Edward J. Doherty ,  David Rein ,  Laura M. Holland

发明人： Frank T. Gentile ,  Tyrone Hazlett ,  Patrick A. Tresco ,  Thomas Flanagan ,  Edward J. Doherty ,  David Rein ,  Laura M. Holland

IPC分类号： A61K9/48 ,  A61F13/00

CPC分类号： A61K9/4816

摘要： Microporous macrocapsules are disclosed which are useful as implantation devices for cell therapy. The macrocapsule comprises living cells that secrete biological substance that are therapeutically useful and that are released from the macrocapsule to the site of implantation. The capsules can have selected permeability characteristics based upon their particular usage and desired viral retentivity characteristics.

摘要翻译： PCT No.PCT / US93 / 11232 Sec。 371日期1995年8月14日 102（e）日期1995年8月14日PCT提交1993年11月16日PCT公布。 公开号WO94 / 10950 PCT 日期1994年5月26日公开了可用作细胞治疗的植入装置的大孔微胶囊。 所述大囊包含分泌生物物质的活细胞，所述活细胞在治疗上有用并从所述宏胶囊释放到植入部位。 胶囊可以根据其特定用途和期望的病毒保持性特征具有选择的渗透性特征。

公开(公告)号：US5935849A

公开(公告)日：1999-08-10

申请号：US279773

申请日：1994-07-20

申请人： Malcolm Schinstine ,  Molly S. Shoichet ,  Frank T. Gentile ,  Joseph P. Hammang ,  Laura M. Holland ,  Brian M. Cain ,  Edward J. Doherty ,  Shelley R. Winn ,  Patrick Aebischer

发明人： Malcolm Schinstine ,  Molly S. Shoichet ,  Frank T. Gentile ,  Joseph P. Hammang ,  Laura M. Holland ,  Brian M. Cain ,  Edward J. Doherty ,  Shelley R. Winn ,  Patrick Aebischer

IPC分类号： A01K67/027 ,  A61K48/00 ,  A61L27/00 ,  A61L27/18 ,  A61L27/22 ,  A61L27/38 ,  C07K14/82 ,  C12N5/00 ,  C12N5/10 ,  C12N15/09 ,  C12N15/12

CPC分类号： A61L27/3839 ,  A61L27/18 ,  A61L27/227 ,  C07K14/82 ,  C12N5/0012 ,  C12N5/0068 ,  A61K48/00 ,  C12N2510/00 ,  C12N2510/04 ,  C12N2533/30 ,  C12N2533/54 ,  C12N2533/74

摘要： This invention relates to methods and compositions of controlling cell distribution within a bioartificial organ by exposing the cells to a treatment that inhibits cell proliferation, promotes cell differentiation, or affects cell attachment to a growth surface within the bioartificial organ. Such treatments include (1) genetically manipulating cells, (2) exposing the cells to a proliferation-inhibiting compound or a differentiation-inducing compound or removing the cells from exposure to a proliferation-stimulating compound or a differentiation-inhibiting compound; exposing the cells to irradiation, and (3) modifying a growth surface of the BAO with ECM molecules, molecules affecting cell proliferation or adhesion, or an inert scaffold, or a combination thereof. These treatments may be used in combination.

摘要翻译： 本发明涉及通过将细胞暴露于抑制细胞增殖，促进细胞分化或影响细胞附着于生物人造器官内的生长表面的处理来控制生物人造器官内的细胞分布的方法和组合物。 这样的处理包括（1）遗传操纵细胞，（2）将细胞暴露于增殖抑制化合物或分化诱导化合物，或除去细胞暴露于增殖刺激化合物或分化抑制化合物; 使细胞暴露于照射，和（3）用ECM分子修饰BAO的生长表面，影响细胞增殖或粘附的分子，或惰性支架或其组合。 这些处理可以组合使用。

公开(公告)号：US5858747A

公开(公告)日：1999-01-12

申请号：US447810

申请日：1995-05-23

申请人： Malcolm Schinstine ,  Molly S. Shoichet ,  Frank T. Gentile ,  Joseph P. Hammang ,  Laura M. Holland ,  Brian M. Cain ,  Edward J. Doherty ,  Shelley R. Winn ,  Patrick Aebischer

发明人： Malcolm Schinstine ,  Molly S. Shoichet ,  Frank T. Gentile ,  Joseph P. Hammang ,  Laura M. Holland ,  Brian M. Cain ,  Edward J. Doherty ,  Shelley R. Winn ,  Patrick Aebischer

IPC分类号： A01K67/027 ,  A61K48/00 ,  A61L27/00 ,  A61L27/18 ,  A61L27/22 ,  A61L27/38 ,  C07K14/82 ,  C12N5/00 ,  C12N5/10 ,  C12N15/09 ,  C12N15/12 ,  C12N11/04 ,  C12N5/06 ,  C12N5/08 ,  C12N11/02

CPC分类号： C12N5/0068 ,  A61L27/18 ,  A61L27/227 ,  A61L27/383 ,  A61L27/3834 ,  A61L27/3839 ,  A61L27/3895 ,  C07K14/82 ,  A61K48/00 ,  C12N2510/00 ,  C12N2510/04 ,  C12N2533/30 ,  C12N2533/54 ,  C12N2533/74

摘要： Methods and compositions are provided for controlling cell distribution within an implantable bioartificial organ by exposing the cells to a treatment that inhibits cell proliferation, promotes cell differentiation, or affects cell attachment to a growth surface within the bioartificial organ. Such treatments include (1) genetically manipulating cells, (2) exposing the cells to a proliferation-inhibiting compound or a differentiation-inducing compound or removing the cells from exposure to a proliferation-stimulating compound or a differentiation-inhibiting compound; exposing the cells to irradiation, and (3) modifying a growth surface of the bioartificial organ with extracellular matrix molecules, molecules affecting cell proliferation or adhesion, or an inert scaffold, or a combination thereof. These treatments may be used in combination. The bioartificial organ typically has a semipermeable membrane encapsulating a cell-containing core, and is preferably immunoisolatory. Cells can be grown on microcarriers and then loaded into the bioartificial organ. The microcarriers may be coated with an extracellular matrix component such as collagen to cause decreased cell proliferation or increased cell differentiation. Microcarriers containing cells can be suspended in a proliferation inhibiting hydrogel matrix prior to encapsulation.

摘要翻译： 提供了用于通过将细胞暴露于抑制细胞增殖，促进细胞分化或影响细胞附着于生物人造器官内的生长表面的处理来控制可植入的生物人造器官内的细胞分布的方法和组合物。 这样的处理包括（1）遗传操纵细胞，（2）将细胞暴露于增殖抑制化合物或分化诱导化合物，或除去细胞暴露于增殖刺激化合物或分化抑制化合物; 将细胞暴露于照射下，和（3）用细胞外基质分子，影响细胞增殖或粘附的分子，或惰性支架或其组合修饰生物人造器官的生长表面。 这些处理可以组合使用。 生物人造器官通常具有包封含细胞核的半透膜，并且优选地是免疫隔离的。 细胞可以在微载体上生长，然后装入生物人造器官。 微载体可以用细胞外基质组分如胶原包被，以引起细胞增殖减少或细胞分化增加。 含有细胞的微载体可以在包封之前悬浮于增殖抑制水凝胶基质中。

公开(公告)号：US5776747A

公开(公告)日：1998-07-07

申请号：US447778

申请日：1995-05-23

申请人： Malcolm Schinstine ,  Molly S. Shoichet ,  Frank T. Gentile ,  Joseph P. Hammang ,  Laura M. Holland ,  Brian M. Cain ,  Edward J. Doherty ,  Shelley R. Winn ,  Patrick Aebischer

发明人： Malcolm Schinstine ,  Molly S. Shoichet ,  Frank T. Gentile ,  Joseph P. Hammang ,  Laura M. Holland ,  Brian M. Cain ,  Edward J. Doherty ,  Shelley R. Winn ,  Patrick Aebischer

IPC分类号： A01K67/027 ,  A61K48/00 ,  A61L27/00 ,  A61L27/18 ,  A61L27/22 ,  A61L27/38 ,  C07K14/82 ,  C12N5/00 ,  C12N5/10 ,  C12N15/09 ,  C12N15/12 ,  C12N11/02 ,  C12N11/04 ,  C12N11/06 ,  C12N11/08

CPC分类号： C12N5/0068 ,  A61L27/18 ,  A61L27/227 ,  A61L27/383 ,  A61L27/3834 ,  A61L27/3839 ,  A61L27/3895 ,  C07K14/82 ,  A61K48/00 ,  C12N2510/00 ,  C12N2510/04 ,  C12N2533/30 ,  C12N2533/54 ,  C12N2533/74

摘要： This invention relates to methods and compositions of controlling cell distribution within a bioartificial organ by exposing the cells to a treatment that inhibits cell proliferation, promotes cell differentiation, or affects cell attachment to a growth surface within the bioartificial organ. Such treatments include (1) genetically manipulating cells, (2) exposing the cells to a proliferation-inhibiting compound or a differentiation-inducing compound or removing the cells from exposure to a proliferation-stimulating compound or a differentiation-inhibiting compound; exposing the cells to irradiation, and (3) modifying a growth surface of the BAO with ECM molecules, molecules affecting cell proliferation or adhesion, or an inert scaffold, or a combination thereof. These treatments may be used in combination. A particular embodiment is directed to derivatizing or adsorbing polyethylene oxide-poly(dimethylsiloxane) copolymer (PEO-PDMS) onto a surface within the bioartificial organ to inhibit cellular attachment.

摘要翻译： 本发明涉及通过将细胞暴露于抑制细胞增殖，促进细胞分化或影响细胞附着于生物人造器官内的生长表面的处理来控制生物人造器官内的细胞分布的方法和组合物。 这样的处理包括（1）遗传操纵细胞，（2）将细胞暴露于增殖抑制化合物或分化诱导化合物，或除去细胞暴露于增殖刺激化合物或分化抑制化合物; 使细胞暴露于照射，和（3）用ECM分子修饰BAO的生长表面，影响细胞增殖或粘附的分子，或惰性支架或其组合。 这些处理可以组合使用。 一个具体实施方案涉及将聚环氧乙烷 - 聚（二甲基硅氧烷）共聚物（PEO-PDMS）衍生或吸附到生物人造器官内的表面上以抑制细胞附着。

公开(公告)号：US5550050A

公开(公告)日：1996-08-27

申请号：US228403

申请日：1994-04-15

申请人： Laura M. Holland ,  Joseph P. Hammang ,  Seth A. Rudnick ,  Michael J. Lysaght ,  Keith E. Dionne

发明人： Laura M. Holland ,  Joseph P. Hammang ,  Seth A. Rudnick ,  Michael J. Lysaght ,  Keith E. Dionne

IPC分类号： A61K9/48 ,  A61K9/00 ,  A61K9/64 ,  A61K35/12 ,  A61K35/23 ,  A61K38/00 ,  A61K45/00 ,  A61K48/00 ,  A61P27/02 ,  C07K14/475 ,  C07K14/48 ,  C12N5/00 ,  C12N5/071 ,  C12N1/36 ,  C12N1/38

CPC分类号： A61K9/0024 ,  A61K35/13 ,  A61K35/22 ,  A61K9/0048 ,  A61K9/0085 ,  C07K14/475 ,  C07K14/48 ,  C12N5/0614 ,  C12N5/0618 ,  A61K38/00 ,  A61K48/00 ,  A61K9/0092 ,  C12N2500/02 ,  C12N2500/34

摘要： This invention provides methods for implanting encapsulated cells in a host comprising exposing cells to restrictive conditions for a sufficient period of time to establish a desired cell property in response to the restrictive conditions and implanting the encapsulated cells in a host, the cell property being substantially maintained following implantation. Also provided are cells produced by exposure to restrictive conditions.

摘要翻译： 本发明提供了用于将包封的细胞植入宿主中的方法，其包括将细胞暴露于限制性条件足够长的时间以响应限制性条件建立所需的细胞特性并将包封的细胞植入宿主中，细胞特性基本保持 植入后。 还提供了通过暴露于限制条件产生的细胞。

公开(公告)号：US5840576A

公开(公告)日：1998-11-24

申请号：US445193

申请日：1995-05-23

申请人： Malcolm Schinstine ,  Molly S. Shoichet ,  Frank T. Gentile ,  Joseph P. Hammang ,  Laura M. Holland ,  Brian M. Cain ,  Edward J. Doherty ,  Shelley R. Winn ,  Patrick Aebischer

发明人： Malcolm Schinstine ,  Molly S. Shoichet ,  Frank T. Gentile ,  Joseph P. Hammang ,  Laura M. Holland ,  Brian M. Cain ,  Edward J. Doherty ,  Shelley R. Winn ,  Patrick Aebischer

IPC分类号： A01K67/027 ,  A61K48/00 ,  A61L27/00 ,  A61L27/18 ,  A61L27/22 ,  A61L27/38 ,  C07K14/82 ,  C12N5/00 ,  C12N5/10 ,  C12N15/09 ,  C12N15/12

CPC分类号： C12N5/0068 ,  A61L27/18 ,  A61L27/227 ,  A61L27/383 ,  A61L27/3834 ,  A61L27/3839 ,  A61L27/3895 ,  C07K14/82 ,  A61K48/00 ,  C12N2510/00 ,  C12N2510/04 ,  C12N2533/30 ,  C12N2533/54 ,  C12N2533/74

摘要： This invention relates to methods and compositions of controlling cell distribution within a bioartificial organ by exposing the cells to a treatment that inhibits cell proliferation, promotes cell differentiation, or affects cell attachment to a growth surface within the bioartificial organ. Such treatments include (1) genetically manipulating cells, (2) exposing the cells to a proliferation-inhibiting compound or a differentiation-inducing compound or removing the cells from exposure to a proliferation-stimulating compound or a differentiation-inhibiting compound; exposing the cells to irradiation, and (3) modifying a growth surface of the BAO with ECM molecules, molecules affecting cell proliferation or adhesion, or an inert scaffold, or a combination thereof. These treatments may be used in combination.

公开(公告)号：US5833979A

公开(公告)日：1998-11-10

申请号：US447771

申请日：1995-05-23

申请人： Malcolm Schinstine ,  Molly S. Shoichet ,  Frank T. Gentile ,  Joseph P. Hammang ,  Laura M. Holland ,  Brian M. Cain ,  Edward J. Doherty ,  Shelley R. Winn ,  Patrick Aebischer

发明人： Malcolm Schinstine ,  Molly S. Shoichet ,  Frank T. Gentile ,  Joseph P. Hammang ,  Laura M. Holland ,  Brian M. Cain ,  Edward J. Doherty ,  Shelley R. Winn ,  Patrick Aebischer

IPC分类号： A01K67/027 ,  A61K48/00 ,  A61L27/00 ,  A61L27/18 ,  A61L27/22 ,  A61L27/38 ,  C07K14/82 ,  C12N5/00 ,  C12N5/10 ,  C12N15/09 ,  C12N15/12 ,  A01N63/00

CPC分类号： C12N5/0068 ,  A61L27/18 ,  A61L27/227 ,  A61L27/383 ,  A61L27/3834 ,  A61L27/3839 ,  A61L27/3895 ,  C07K14/82 ,  A61K48/00 ,  C12N2510/00 ,  C12N2510/04 ,  C12N2533/30 ,  C12N2533/54 ,  C12N2533/74

摘要： This invention relates to methods and compositions of controlling cell distribution within a bioartificial organ by exposing the cells to a treatment that inhibits cell proliferation, promotes cell differentiation, or affects cell attachment to a growth surface within the bioartificial organ. Such treatments include (1) genetically manipulating cells, (2) exposing the cells to a proliferation-inhibiting compound or a differentiation-inducing compound or removing the cells from exposure to a proliferation-stimulating compound or a differentiation-inhibiting compound; exposing the cells to irradiation, and (3) modifying a growth surface of the BAO with ECM molecules, molecules affecting cell proliferation or adhesion, or an inert scaffold, or a combination thereof. These treatments may be used in combination.

公开(公告)号：US5795790A

公开(公告)日：1998-08-18

申请号：US448201

申请日：1995-05-23

申请人： Malcolm Schinstine ,  Molly S. Shoichet ,  Frank T. Gentile ,  Joseph P. Hammang ,  Laura M. Holland ,  Brian M. Cain ,  Edward J. Doherty ,  Shelley R. Winn ,  Patrick Aebischer

发明人： Malcolm Schinstine ,  Molly S. Shoichet ,  Frank T. Gentile ,  Joseph P. Hammang ,  Laura M. Holland ,  Brian M. Cain ,  Edward J. Doherty ,  Shelley R. Winn ,  Patrick Aebischer

IPC分类号： A01K67/027 ,  A61K48/00 ,  A61L27/00 ,  A61L27/18 ,  A61L27/22 ,  A61L27/38 ,  C07K14/82 ,  C12N5/00 ,  C12N5/10 ,  C12N15/09 ,  C12N15/12 ,  A61K35/12 ,  C12N11/02 ,  C12N11/04

CPC分类号： C12N5/0068 ,  A61L27/18 ,  A61L27/227 ,  A61L27/383 ,  A61L27/3834 ,  A61L27/3839 ,  A61L27/3895 ,  C07K14/82 ,  A61K48/00 ,  C12N2510/00 ,  C12N2510/04 ,  C12N2533/30 ,  C12N2533/54 ,  C12N2533/74

摘要： Methods and compositions are provided for controlling cell distribution within a bioartificial organ by exposing the cells to a treatment that inhibits cell proliferation, promotes cell differentiation, or affects cell attachment to a growth surface within the bioartificial organ. Such treatments include (1) genetically manipulating cells, (2) exposing the cells to a proliferation-inhibiting compound or a differentiation-inducing compound or removing the cells from exposure to a proliferation-stimulating compound or a differentiation-inhibiting compound; exposing the cells to irradiation, and (3) modifying a growth surface of the bioartificial organ with extracellular matrix molecules, molecules affecting cell proliferation or adhesion, or an inert scaffold, or a combination thereof. These treatments may be used in combination. In a preferred treatment, cells are exposed to and then removed from exposure to a proliferation-stimulating and differentiation inhibiting compound prior to encapsulation of the cells in a semipermeable biocompatible jacket to form a bioartificial organ. Upon in vivo implantation of the bioartificial organ in a host, cellular proliferation is inhibited and cellular differentiation is promoted.

摘要翻译： 提供了用于通过将细胞暴露于抑制细胞增殖，促进细胞分化或影响细胞附着于生物人造器官内的生长表面的处理来控制生物人造器官内的细胞分布的方法和组合物。 这样的处理包括（1）遗传操纵细胞，（2）将细胞暴露于增殖抑制化合物或分化诱导化合物，或除去细胞暴露于增殖刺激化合物或分化抑制化合物; 将细胞暴露于照射下，和（3）用细胞外基质分子，影响细胞增殖或粘附的分子，或惰性支架或其组合修饰生物人造器官的生长表面。 这些处理可以组合使用。 在优选的治疗中，将细胞暴露于暴露于增殖刺激和分化抑制化合物之前，然后将细胞包封在半透性生物相容性护套中以形成生物人造器官。 在宿主体内植入生物人造器官后，抑制细胞增殖并促进细胞分化。

公开(公告)号：US06337088B1

公开(公告)日：2002-01-08

申请号：US08465392

申请日：1995-06-05

申请人： Frank T. Gentile ,  Patrick A. Tresco ,  Tyrone Hazlett ,  Thomas Flanagan ,  Edward J. Doherty ,  David Rein ,  Laura M. Holland

发明人： Frank T. Gentile ,  Patrick A. Tresco ,  Tyrone Hazlett ,  Thomas Flanagan ,  Edward J. Doherty ,  David Rein ,  Laura M. Holland

IPC分类号： A01N6300

CPC分类号： A61K9/0024

摘要： A method for determining the viral retentivity of an external jacket of an implantable permselective macrocapsule. Viral retentivity describes the ability of an external jacket to retard the transport of virus particles across the jacket.

摘要翻译： 一种用于确定可植入的选择性选择性大型胶囊的外部护套的病毒保持性的方法。 病毒保持性描述外部夹克阻止病毒颗粒穿过护套的运输的能力。