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    In vitro and in vivo proliferation and use of multipotent neural stem cells and their progeny
    42.
    发明申请
    In vitro and in vivo proliferation and use of multipotent neural stem cells and their progeny 失效
    体外和体内增殖和使用多能神经干细胞及其后代

    公开(公告)号：US20030049837A1

    公开(公告)日：2003-03-13

    申请号：US09925911

    申请日：2001-08-09

    发明人： Samuel Weiss ,  Brent Reynolds ,  Joseph P. Hammang ,  E. Edward Baetge

    IPC分类号： C12N005/08

    CPC分类号： G01N33/5058 ,  A01K2217/05 ,  A61K48/00 ,  C07K14/47 ,  C07K14/475 ,  C07K14/82 ,  C12N5/0623 ,  C12N9/0065 ,  C12N9/2471 ,  C12N2500/25 ,  C12N2500/46 ,  C12N2500/90 ,  C12N2501/11 ,  C12N2501/148 ,  C12N2501/15 ,  C12N2501/392 ,  C12N2501/91 ,  C12N2503/02 ,  C12N2510/00 ,  C12Y302/01023 ,  G01N33/5008 ,  G01N33/5017 ,  G01N33/5023 ,  G01N33/5073 ,  G01N2500/00 ,  G01N2510/00

    摘要： Nucleic acids may be obtained from neural cell cultures produced by using growth factors to induce the proliferation of multipotent neural stem cells. The resultant progeny may be passaged repeatedly to produce a sufficient number of cells to obtain representative nucleic acid samples. Clonal cultures may be produced. Nucleic acids may be obtained from both cultured normal and dysfunctional neural cells and from neural cell cultures at various stages of development. This information allows for the identification of the sequence of gene expression during neural development and can be used to reveal the effects of biological agents on gene expression in neural cells. Additionally, nucleic acids derived from dysfunctional tissue can be compared with that of normal tissue to identify genetic material which may be the cause of the dysfunction. This information could then be used in the design of therapies to treat the neurological disorder. A further use of the technology would be in the diagnosis of genetic disorders or for use in identifying neural cells at a particular stage in development.

    摘要翻译： 核酸可以从通过使用生长因子诱导多能神经干细胞增殖产生的神经细胞培养物获得。 所得后代可以重复传代以产生足够数量的细胞以获得代表性的核酸样品。 可能产生克隆培养物。 核酸可以从培养的正常和功能障碍的神经细胞和来自神经细胞培养物的不同发育阶段获得。 该信息允许在神经发育期间鉴定基因表达序列，并且可以用于揭示生物剂对神经细胞中的基因表达的影响。 另外，来自功能障碍组织的核酸可以与正常组织的核酸进行比较，以鉴定可能是功能障碍的原因的遗传物质。 然后可以将该信息用于设计治疗神经障碍的治疗。 该技术的进一步使用将在于遗传疾病的诊断或用于在发育的特定阶段鉴定神经细胞。

    Hepatocytes for therapy and drug screening made from embryonic stem cells
    43.
    发明申请
    Hepatocytes for therapy and drug screening made from embryonic stem cells 有权
    用胚胎干细胞进行治疗和药物筛选的肝细胞

    公开(公告)号：US20030003573A1

    公开(公告)日：2003-01-02

    申请号：US10087142

    申请日：2002-03-01

    发明人： Lakshmi Rambhatle ,  Melissa K. Carpenter

    IPC分类号： C12N005/08

    CPC分类号： C12N5/067 ,  C12N2500/30 ,  C12N2500/36 ,  C12N2501/11 ,  C12N2501/115 ,  C12N2501/12 ,  C12N2501/148 ,  C12N2501/33 ,  C12N2501/335 ,  C12N2501/385 ,  C12N2501/39 ,  C12N2503/02 ,  C12N2506/02 ,  C12N2533/92

    摘要： It has been discovered that when pluripotent stem cells are cultured in the presence of a hepatocyte differentiation agent, a population of cells is derived that has a remarkably high proportion of cells with phenotypic characteristics of liver cells. In one example, human embryonic stem cells are allowed to form embryoid bodies, and then combined with the differentiation agent n-butyrate, optionally supplemented with maturation factors. In another example, n-butyrate is added to human embryonic stem cells in feeder-free culture. Either way, a remarkably uniform cell population is obtained, which is predominated by cells with morphological features of hepatocytes, expressing surface markers characteristic of hepatocytes, and having enzymatic and biosynthetic activity important for liver function. Since stem cells readily proliferate in culture, this system provides an abundant source of cells of the hepatocyte lineage for a variety of applications, such as drug screening, and replenishing liver function in the context of clinical treatment.

    摘要翻译： 已经发现，当在肝细胞分化剂存在下培养多能干细胞时，衍生出具有非常高比例的具有肝细胞表型特征的细胞的细胞群。 在一个实例中，允许人胚胎干细胞形成胚状体，然后与分选剂正丁酸酯组合，任选地补充成熟因子。 在另一个实例中，在无饲养细胞培养物中将正丁酸加入到人胚胎干细胞中。 无论哪种方式，获得了显着均匀的细胞群，其由具有肝细胞形态特征的细胞占主导，表达肝细胞特征的表达标志物，并具有对肝功能重要的酶和生物合成活性。 由于干细胞在培养物中容易增殖，所以该系统为各种应用提供了丰富的肝细胞谱系来源，例如药物筛选，并在临床治疗的背景下补充肝功能。

    Isolation propagation and directed differentiation of stem cells from embryonic and adult central nervous system of mammals
    48.
    发明授权
    Isolation propagation and directed differentiation of stem cells from embryonic and adult central nervous system of mammals 失效
    干细胞从哺乳动物的胚胎和成年中枢神经系统的分离繁殖和定向分化

    公开(公告)号：US5753506A

    公开(公告)日：1998-05-19

    申请号：US719450

    申请日：1996-09-25

    申请人： Karl K. Johe

    发明人： Karl K. Johe

    IPC分类号： A61K35/12 ,  C12N5/0797 ,  G01N33/50 ,  G01N33/94 ,  C12N5/08

    CPC分类号： G01N33/5073 ,  C12N5/0623 ,  G01N33/5008 ,  G01N33/502 ,  G01N33/5058 ,  G01N33/9413 ,  A61K35/12 ,  C12N2500/90 ,  C12N2501/11 ,  C12N2501/115 ,  C12N2501/13 ,  C12N2501/148 ,  C12N2501/395 ,  C12N2501/91 ,  C12N2506/02 ,  C12N2510/02

    摘要： The present invention reveals an in vitro procedure by which a homogeneous population of multipotential precursor cells from mammalian embryonic neuroepithelium (CNS stem cells) can be expanded up to 10.sup.9 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 proportions 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. These cells should be an important tool for many cell- and gene-based therapies for neurological disorders.

    摘要翻译： 本发明揭示了一种体外方法，通过该方法，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109倍，同时保持其多能分化为神经元，少突胶质细胞和星形胶质细胞的能力。 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，已经鉴定出四种因素 - PDGF，CNTF，LIF和T3-，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。 这些细胞应该是许多基于细胞和基因的神经障碍治疗的重要工具。