Methods comprising apoptosis inhibitors for the generation of transgenic pigs

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Stem Cell Related Patent Number US6949380

Title:Transdifferentiation of epidermal basal cells into neural progenitor cells, neuronal cells and/or glial cells
Inventors:Lévesque, Michel F.; Beverly Hills, CA, USA
Neuman, Toomas; Santa Monica, CA, USA
Summary:Described herein is a method of transdifferentiating epidermal basal cells via exposure to fetuin, noggin, chordin gremlin or follistatin antagonist of bone morphogenetic protein. This invention relates to a method of transdifferentiating an epidermal basal cell into a cell having one or more morphological, physiological and/or immunological features of a neural progenitor, neuronal, or glial cell by culturing a proliferating epidermal basal cell population derived from the skin of a mammalian subject, exposing the epidermal basal cell(s) to an antagonist of bone morphogenetic protein (BMP) such as fetuin, noggin, chordin, gremlin, or follistatin, and growing the cell(s) in the presence of at least one antisense oligonucleotide comprising a segment of a human MSX1 gene and/or a segment of a human HES1 gene, or homologous non-human counterpart thereof. Further disclosed is a transdifferentiated cell of epidermal origin and cell cultures derived from such a cell. Also included are methods of using the transdifferentiated cell(s) and cell cultures to identify a novel nerve growth factor or to screen a potential chemotherapeutic agent by detecting the presence or absence of an effect, in vitro, on a morphological, physiological or molecular biological property of the transdifferentiated cell(s). Also included are methods of using the transdifferentiated cell(s) and cell cultures to screen a potential chemotherapeutic agent to treat a nervous system disorder of genetic origin, as is a kit useful for practicing such methods. Therapeutic applications in the treatment of stroke and Alzheimer's disease are included.
Abstract:Disclosed is a method of transdifferentiating an epidermal basal cell into a cell having one or more morphological, physiological and/or immunological features of a neural progenitor, neuronal, or glial cell by culturing a proliferating epidermal basal cell population derived from the skin of a mammalian subject; exposing the epidermal basal cell(s) to an antagonist of bone morphogenetic protein (BMP), such as fetuin, noggin, chordin, gremlin, or follistatin; and growing the cell(s) in the presence of at least one antisense oligonucleotide comprising a segment of a human MSX1 gene and/or a segment of a human HES1 gene, or homologous non-human counterpart of either of these. Also disclosed is a transdifferentiated cell of epidermal origin and cell cultures derived therefrom. In addition, methods of using the inventive transdifferentiated cell(s) and cell cultures to identify a novel nerve growth factor or to screen a potential chemotherapeutic agent by detecting the presence or absence of an effect, in vitro, on a morphological, physiological and/or molecular biological property of the transdifferentiated cell(s) are described, as is a method of using the transdifferentiated cell(s) and cell cultures to screen a potential chemotherapeutic agent to treat a nervous system disorder of genetic origin. A kit useful for practicing the methods is disclosed
US Patent Website:Click Here for Full Text of Patent
Title Number:US6949380
Application Number:US2000000488491
Date Filed:20/01/2000
Date Published:27/09/2005
Assignee:Cedars-Sinai Medical Center, Los Angeles, CA, USA


 
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