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    Controlling proliferation of cells before and after encapsulation in a bioartificial organ by gene transformation
    4.
    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

    Applicant: 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

    Inventor： 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: 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 classification number: A61L27/3839 ,  A61L27/18 ,  A61L27/227 ,  C07K14/82 ,  C12N5/0012 ,  C12N5/0068 ,  A61K48/00 ,  C12N2510/00 ,  C12N2510/04 ,  C12N2533/30 ,  C12N2533/54 ,  C12N2533/74

    Abstract: 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.

    Abstract translation: 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。

    Compositions for the delivery of biologically active molecules using genetically altered cells contained in biocompatible immunoisolatory capsules
    6.
    发明授权
    Compositions for the delivery of biologically active molecules using genetically altered cells contained in biocompatible immunoisolatory capsules 失效
    使用包含在生物相容性免疫隔离胶囊中的遗传改变细胞递送生物活性分子的组合物

    公开(公告)号：US06264941B1

    公开(公告)日：2001-07-24

    申请号：US09236246

    申请日：1999-01-25

    Applicant: Edward E. Baetge ,  Joseph P. Hammang ,  Frank T. Gentile ,  Mark D. Lindner ,  Shelley R. Winn ,  Dwaine F. Emerich

    Inventor： Edward E. Baetge ,  Joseph P. Hammang ,  Frank T. Gentile ,  Mark D. Lindner ,  Shelley R. Winn ,  Dwaine F. Emerich

    IPC: A61K4800

    CPC classification number: A61K9/0092 ,  A61K9/0024 ,  A61K9/0085 ,  A61K38/00 ,  A61K48/00 ,  C07K14/48 ,  C07K14/70 ,  C12N15/87

    Abstract: This invention provides improved devices and methods for long-term, stable expression of a biologically active molecule using a biocompatible capsule containing genetically engineered cells for the effective delivery of biologically active molecules to effect or enhance a biological function within a mammalian host. The novel capsules of this invention are biocompatible and are easily retrievable. This invention specifically provides improved methods and compositions which utilize cells transfected with recombinant DNA molecules comprising DNA sequences coding for biologically active molecules operatively linked to promoters that are not subject to down regulation in vivo upon implantation into a mammalian host. Furthermore, the methods of this invention allow for the long-term, stable and efficacious delivery of biologically active molecules from living cells to specific sites within a given mammal. In addition, this invention provides a general means for maintaining, for extended periods of time, the in vivo expression of transgenes.

    Abstract translation: 本发明提供改进的装置和方法，用于使用包含基因工程细胞的生物相容性胶囊长期稳定地表达生物活性分子，用于有效递送生物活性分子以实现或增强哺乳动物宿主内的生物学功能。 本发明的新颖胶囊是生物相容的并且易于回收。 本发明具体提供改进的方法和组合物，其利用重组DNA分子转染的细胞，所述重组DNA分子包含编码与植入哺乳动物宿主体内不受体内下调的启动子有效连接的生物活性分子的DNA序列。 此外，本发明的方法允许将生物活性分子从活细胞长期，稳定和有效地递送到给定哺乳动物内的特定位点。 此外，本发明提供了用于长时间维持转基因的体内表达的一般方法。

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