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    Controlling proliferation of cells before and after encapsulation in a bioartificial organ by gene transformation
    1.
    发明授权
    Controlling proliferation of cells before and after encapsulation in a bioartificial organ by gene transformation 失效
    通过基因转化控制生物人工器官中包封前后细胞的增殖

    公开(公告)号：US5843431A

    公开(公告)日：1998-12-01

    申请号：US432698

    申请日：1995-05-09

    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 ,  C12N11/00 ,  C12N11/10

    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： 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. Cells can be transformed with a proliferation-promoting gene such as the oncogene, SV40, linked to a regulatable promoter such as the Mx1 promoter, the promotor is activated in vitro to express the gene to result in cell proliferation, and the promotor is inactivated before or after insertion of the cells in the bioartificial organ to inhibit expression of the gene to reduce or stop cell proliferation in vivo. The promoter can be reactivated in vivo to again express the gene to result in further cell proliferation. The gene may be a proliferation-suppressing gene such as p53 gene or RB gene, or a differentiation-inducing gene such as high mobility group chromosomal protein 14. Inhibiting gene expression in vitro causes cell proliferation, and inducing gene expression reduces or stops cell proliferation in vivo.

    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。 可以用增殖促进基因转化细胞，例如与可调节启动子如Mx1启动子连接的癌基因SV40，启动子在体外被激活以表达基因以导致细胞增殖，并且启动子在 或在细胞插入生物人造器官中以抑制基因表达以减少或停止体内细胞增殖。 启动子可以在体内再活化以再次表达基因以导致进一步的细胞增殖。 该基因可以是增殖抑制基因如p53基因或RB基因，或分化诱导基因如高迁移率组染色体蛋白14.体外抑制基因表达引起细胞增殖，诱导基因表达降低或停止细胞增殖 体内。

    Apparatus and method for storage and transporation of bioartificial organs
    6.
    发明授权
    Apparatus and method for storage and transporation of bioartificial organs 失效
    生物人造器官储存和运输的装置和方法

    公开(公告)号：US5681740A

    公开(公告)日：1997-10-28

    申请号：US463658

    申请日：1995-06-05

    申请人： Kenneth A. Messier ,  Nicholas F. Warner

    发明人： Kenneth A. Messier ,  Nicholas F. Warner

    IPC分类号： A01N1/02 ,  C12M1/24

    CPC分类号： A01N1/02 ,  A01N1/0263

    摘要： Bioartificial organ storage and transport apparatus having a media storage container. The apparatus is designed to securely maintain a bioartificial organ within the container in a sealed environment. The apparatus may also allow for gas exchange and media exchange to ensure the viability of the bioartificial organ. In addition, the apparatus may use a secondary container and cap, designed to allow access to the media storage container and allow for gas exchange and media exchange.

    摘要翻译： 具有介质储存容器的生物人造器官储存和运输装置。 该设备被设计成在密封的环境中可靠地将生物人造器官保持在容器内。 该装置还可以允许气体交换和介质交换以确保生物人造器官的活力。 此外，该设备可以使用次级容器和盖子，其被设计成允许进入介质存储容器并允许进行气体交换和介质交换。

    Bioartificial organ containing cells encapsulated in a permselective polyether suflfone membrane
    8.
    发明授权
    Bioartificial organ containing cells encapsulated in a permselective polyether suflfone membrane 失效
    含有细胞的生物人工器官包被在选择性聚醚砜膜中

    公开(公告)号：US5837234A

    公开(公告)日：1998-11-17

    申请号：US488317

    申请日：1995-06-07

    申请人： Frank T. Gentile ,  Shelley R. Winn ,  Michael Lysaght ,  Ulrich Baurmeister ,  Friedbert Wechs ,  Henning Rottger

    发明人： Frank T. Gentile ,  Shelley R. Winn ,  Michael Lysaght ,  Ulrich Baurmeister ,  Friedbert Wechs ,  Henning Rottger

    IPC分类号： A61K9/00 ,  A61K9/52 ,  A61K35/12 ,  A61K35/22 ,  A61K35/23 ,  A61K35/33 ,  A61K48/00 ,  B01D69/14 ,  C07K14/475 ,  C12N11/04 ,  C12N5/00 ,  C12N11/08 ,  A61F2/00

    CPC分类号： A61K9/0092 ,  A61K35/22 ,  A61K35/33 ,  A61K9/0024 ,  A61L27/18 ,  A61L27/3804 ,  A61L27/54 ,  A61L27/56 ,  B01D69/141 ,  C07K14/475 ,  C12N11/04 ,  A61K48/00 ,  A61L2300/64

    摘要： A bioartificial organ for implanting to provide a therapeutic effect is prepared containing a core of living cells encapsulated in a foam-like membrane having three regions: a dense, fine-pored, permselective inner region, a middle region that lacks macrovoids and a fine-pored outer region. The membrane has a molecular weight cutoff that permits passage to nutrients to the cells but not passage of the cells. Preferably, the membrane is made of polyether sulfone, pores range in size between 0.02 .mu.m and 2.0 .mu.m and have polyhedrally symmetric boundaries and are arranged asymmetrically from one surface to the other. The membrane has an asymmetry factor AF relative to the maximum pore diameter of 0.01 to 2.0 and a ratio of the maximum mean free path length to the diameter of the largest pore of greater than 3. The membrane can be hydrophobic or hydrophilic. The bioartificial organ is formed by coextrusion or by stepwise assembly by forming the cell core and then applying the membrane. A polyether sulfone membrane is prepared from a solution containing by weight 12 to 35% polyether sulfone and 15 to 65% .epsilon.-caprolactam, and optionally 0 to 85% latent solvent, 0 to 15% thickner, to 5% non-solvent and 0 to 1% auxiliaries. Cells encapsulated can be cells that produce a neurotransmitter such as dopamine or a biologically active factor such as CNTF, NGF, GDNF, endorphins, catecholamines or enkephalins.

    摘要翻译： 制备用于植入以提供治疗效果的生物人造器官，其包含封装在泡沫状膜中的活细胞核，其具有三个区域：致密，细孔，选择性选择性内部区域，缺乏大孔的中间区域， 外面的区域。 膜具有分子量截留值，允许通过营养物质进入细胞，但不能通过细胞。 优选地，膜由聚醚砜制成，孔的尺寸范围在0.02μm至2.0μm之间，具有多边形对称边界并且从一个表面到另一个表面不对称地布置。 该膜具有相对于最大孔径为0.01至2.0的不对称因子AF，并且最大平均自由程长度与最大孔的直径之比大于3。膜可以是疏水的或亲水的。 生物人造器官通过共挤出或通过形成细胞核然后施加膜逐步组装而形成。 聚醚砜膜由含有12-35％聚醚砜和15-65％ε-己内酰胺，和任选0-85％潜溶剂，0-15％增稠剂至5％非溶剂和0- 至1％的助剂。 包封的细胞可以是产生神经递质例如多巴胺或生物活性因子如CNTF，NGF，GDNF，内啡肽，儿茶酚胺或脑啡肽的细胞。

    Membrane formed by an acrylonitrile-based polymer
    9.
    发明授权
    Membrane formed by an acrylonitrile-based polymer 失效
    由丙烯腈基聚合物形成的膜

    公开(公告)号：US5720969A

    公开(公告)日：1998-02-24

    申请号：US535213

    申请日：1996-01-16

    申请人： Frank Gentile ,  Molly Shoichet ,  Milton Harris

    发明人： Frank Gentile ,  Molly Shoichet ,  Milton Harris

    IPC分类号： B01D71/42 ,  C08F8/00 ,  C08F8/12 ,  C08G69/00 ,  C08G69/04 ,  C08G81/02 ,  C08J5/18 ,  C08J5/22 ,  C08L71/02 ,  C08L20/44 ,  C08L81/02 ,  C12N11/04 ,  C12N11/08

    CPC分类号： C08L71/02 ,  C08F8/12 ,  C08G81/025 ,  C08J5/2268 ,  C08J2327/06 ,  C08J2371/02

    摘要： A permselective graft polymer is disclosed that is formed by converting into intermediate reactive sites a portion of the cyano groups of a backbone polymer and grafting polyalkylene oxide polymer chains to the backbone polymer through the reactive sites. Either the backbone polymer of a polymer resin or a permselective polymer membrane can be grafted. When a resin is used, it is formed into a permselective polymer membrane using known methods. The resulting permselective membrane can be formed into hollow fibers or flat sheets for the encapsulation of living cells. The encapsulated cells are then implanted into a patient in need of the biologically-active factors produced by the cells. The permselective graft polymer membrane exhibits good molecular diffusion with minimal protein adsorption.

    摘要翻译： 公开了通过将主链聚合物的一部分氰基转化为中间反应性位点并通过反应性位点将聚环氧烷聚合物链接枝到主链聚合物而形成的选择性选择性接枝聚合物。 聚合物树脂或选择性聚合物膜的主链聚合物可以被接枝。 当使用树脂时，使用已知的方法将其形成为选择性选择性聚合物膜。 所得到的选择性渗透膜可以形成用于活细胞包封的中空纤维或平板。 然后将包封的细胞植入需要由细胞产生的生物活性因子的患者体内。 选择性接枝聚合物膜表现出良好的分子扩散和最小的蛋白质吸附。