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    • 52. 发明申请
    • ISOLATION, PROPAGATION, AND DIRECTED DIFFERENTIATION OF STEM CELLS FROM CENTRAL NERVOUS SYSTEM OF MAMMALS
    • 干细胞从中央神经系统分离,传播和指导的差异
    • WO1997044442A1
    • 1997-11-27
    • PCT/US1997007669
    • 1997-05-07
    • NEURALSTEM BIOPHARMACEUTICALSJOHE, Karl, K.
    • NEURALSTEM BIOPHARMACEUTICALS
    • C12N05/08
    • G01N33/5073A61K35/12C12N5/0623C12N2500/90C12N2501/11C12N2501/115C12N2501/13C12N2501/148C12N2501/395C12N2501/91C12N2506/02C12N2510/02G01N33/5008G01N33/502G01N33/5058G01N33/9413
    • The present invention reveals an in vitro procedure by which an homogeneous population of multipotential precursor cells from mammalian embryonic neuroepithelium (CNS stem cells) can be expanded up to 10 fold in culture while maintaining their multipotential capacity to differentiate into neurons, oligodendrocytes, and astrocytes. Chemically defined conditions are presented that enable a large number of neurons, up to 50 % of the expanded cells, to be derived from the stem cells. In addition, four factors -- PDGF, CNTF, LIF and T3 -- have been identified, which, individually, generate significantly higher proportion of neurons, astrocytes, or oligodendrocytes. These defined procedures permit a large-scale preparation of the mammalian CNS stem cells, neurons, astrocytes, and oligodendrocytes under chemically defined conditions with efficiency and control. The present invention also reveals in vitro cultures of region-specific, terminally differentiated, mature neurons derived from cultures of mammalian multipotential CNS stem cells and an in vitro procedure by which the differentiated neurons may be generated.
    • 本发明揭示了一种体外方法,其中来自哺乳动物胚胎神经上皮(CNS干细胞)的多潜能前体细胞的均质群体可以在培养物中扩增至10 9倍,同时保持其多能力分化为神经元,少突胶质细胞, 和星形胶质细胞。 提出了化学上定义的条件,使得能够从干细胞中获得多达50%的扩增细胞的大量神经元。 此外,已经鉴定了四个因子 - PDGF,CNTF,LIF和T3-个体,其分别产生显着更高比例的神经元,星形胶质细胞或少突胶质细胞。 这些定义的方法允许在化学定义的条件下大量制备哺乳动物CNS干细胞,神经元,星形胶质细胞和少突胶质细胞,其效率和对照。 本发明还揭示衍生自哺乳动物多潜能CNS干细胞培养物的区域特异性,终末分化的成熟神经元的体外培养物,以及可产生分化的神经元的体外方法。