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    Protein sustaining undifferentiated stem cells as such
    1.
    发明申请
    Protein sustaining undifferentiated stem cells as such 审中-公开
    蛋白质维持未分化的干细胞

    公开(公告)号：US20050221477A1

    公开(公告)日：2005-10-06

    申请号：US10507343

    申请日：2002-03-11

    申请人： Hideo Ema ,  Hiromitsu Nakauchi ,  Mitsujiro Osawa

    发明人： Hideo Ema ,  Hiromitsu Nakauchi ,  Mitsujiro Osawa

    IPC分类号： A61P43/00 ,  C07K14/47 ,  C12N5/0789 ,  C12N5/08 ,  C07K7/06

    CPC分类号： C12N5/0647 ,  C07K14/47 ,  C12N2501/125 ,  C12N2501/145 ,  C12N2501/22 ,  C12N2501/23 ,  C12N2501/26 ,  C12N2501/415

    摘要： The sustaining stem cells for example, hematopoietic stem cells while holding in the undifferentiated state and maintaining pluripotency by providing a polypeptide having a WIF domain for example, WIF-1 to the stem cells has been successfully achieved. This polypeptide preferably also contains an EGF-like repeat. This result has been achieved by providing a polypeptide preferably having the WIF domain together with a stem cell survival factor such as SCF. Thus, it becomes possible to easily provide a large amount of stem cells for example, hematopoietic stem cells containing functional precursor cells. It has also become possible to more efficiently transfer a gene into the stem cells. Because it is homogeneous and almost free from impurities, the stem cell composition can remarkably relieve side effects for example, infection, which occur in conventional therapies using hematopoietic stem cells.

    摘要翻译： 维持性干细胞例如造血干细胞同时保持未分化状态并通过向干细胞提供具有WIF结构域例如WIF-1的多肽来保持多能性已被成功地实现。 该多肽优选还含有EGF样重复。 该结果已经通过提供优选具有WIF结构域的多肽与干细​​胞存活因子如SCF来实现。 因此，可以容易地提供大量的干细胞，例如含有功能性前体细胞的造血干细胞。 也可以更有效地将基因转移到干细胞中。 因为它是均质的并且几乎没有杂质，干细胞组合物可以显着地减轻使用造血干细胞的常规疗法中发生的副作用，例如感染。

    Organ regeneration method utilizing blastocyst complementation
    2.
    发明申请
    Organ regeneration method utilizing blastocyst complementation 审中-公开
    器官再生方法利用囊胚互补

    公开(公告)号：US20100122360A1

    公开(公告)日：2010-05-13

    申请号：US12583559

    申请日：2009-08-21

    申请人： Hiromitsu Nakauchi ,  Toshihiro Kobayashi ,  Younsu Lee ,  Joichi Usui ,  Tomoyuki Yamaguchi ,  Sanae Hamanaka

    发明人： Hiromitsu Nakauchi ,  Toshihiro Kobayashi ,  Younsu Lee ,  Joichi Usui ,  Tomoyuki Yamaguchi ,  Sanae Hamanaka

    IPC分类号： A01K67/00 ,  C12N5/07 ,  A01N1/02

    CPC分类号： A01K67/0271 ,  A01K2207/20 ,  A61L27/3834

    摘要： An object of the present invention is to produce a mammalian organ having a complicated cellular composition composed of multiple kinds of cells, such as kidney, pancreas, thymus and hair, in the living body of a non-human animal. The inventors of the present invention applied the chimeric animal assay described above, to a novel solid organ production method. More specifically, the inventors has shown that a model mouse which is deficient of kidney, pancreas, thymus or hair due to the dysfunction of the metanephric mesenchyme that is differentiated into most of an adult kidney, is rescued by blastocyst complementation by the chimeric animal assay, and whereby a kidney, a pancreas, thymus or hair can be newly produced.

    摘要翻译： 本发明的目的是在非人动物的活体中制备由多种细胞如肾，胰腺，胸腺和毛发组成的细胞组成复杂的哺乳动物器官。 本发明的发明人将上述嵌合动物实验应用于新型的固体器官生产方法。 更具体地，本发明人已经表明，由分化成大部分成年肾脏的间质间质的功能障碍引起的肾，胰腺，胸腺或毛发缺陷的模型小鼠通过嵌合动物试验通过囊胚互补来拯救 ，由此可以新生产肾，胰腺，胸腺或毛发。

    METHOD FOR PRODUCING FOUNDER ANIMAL FOR REPRODUCING ANIMAL HAVING LETHAL PHENOTYPE CAUSED BY GENE MODIFICATION
    4.
    发明申请
    METHOD FOR PRODUCING FOUNDER ANIMAL FOR REPRODUCING ANIMAL HAVING LETHAL PHENOTYPE CAUSED BY GENE MODIFICATION 审中-公开
    生产基因动物的方法，用于复制由基因修饰引起的具有原始基因的动物

    公开(公告)号：US20110067125A1

    公开(公告)日：2011-03-17

    申请号：US12918694

    申请日：2009-02-23

    申请人： Hiromitsu Nakauchi ,  Toshihiro Kobayashi

    发明人： Hiromitsu Nakauchi ,  Toshihiro Kobayashi

    IPC分类号： A01K67/027 ,  C12N15/06

    CPC分类号： A61K31/7088 ,  A01K67/0271 ,  A01K67/0275 ,  A01K2207/00 ,  A01K2217/00 ,  A01K2227/105 ,  A01K2267/03 ,  C12N15/8509

    摘要： An object of the present invention is to provide a method which constantly enables organ regeneration for the purpose of achieving organ regeneration with higher efficiency. It has been discovered that, in a blastocyst complementation method, a next generation is born when a deficiency in an organ, such as pancreas and kidney, is complemented by injection of ES cells into a generated blastocyst, and further discovered that a transgenic animal having a pancreas or a kidney thus complemented can transmit the phenotype to the next generation as a founder. This discovery has revealed that organ regeneration can be accomplished by using such a founder. Thus, the present invention achieved the above-described object.

    摘要翻译： 本发明的目的是提供一种能够以更高效率实现器官再生的目的，能够使器官再生持续的方法。 已经发现，在囊胚互补方法中，当通过将ES细胞注射到产生的囊胚中来补充器官如胰腺和肾脏的缺乏时，产生下一代，并且还发现具有 如此补充的胰腺或肾脏可以将表型传播给下一代作为创始人。 这一发现揭示了器官再生可以通过使用这样的创始人来完成。 因此，本发明实现了上述目的。

    Self-renewing pluripotent hepatic stem cells
    5.
    发明授权
    Self-renewing pluripotent hepatic stem cells 失效
    自我更新多能肝干细胞

    公开(公告)号：US07150990B2

    公开(公告)日：2006-12-19

    申请号：US10093311

    申请日：2002-03-06

    申请人： Hiromitsu Nakauchi ,  Atsushi Suzuki ,  Hideki Taniguchi ,  Katashi Fukao

    发明人： Hiromitsu Nakauchi ,  Atsushi Suzuki ,  Hideki Taniguchi ,  Katashi Fukao

    IPC分类号： C12N5/06 ,  C12N5/10 ,  A01N63/00 ,  C12N5/08

    CPC分类号： C12N5/0676 ,  A61K35/12 ,  C12N5/0672 ,  C12N2506/02 ,  C12N2506/14 ,  Y02A50/463

    摘要： The present invention provides clonal pluripotent hepatic stem cells using flow cytometry and in vitro single-cell-based assays. These cells possess multilineage differentiation potential and self-renewing capability. These cells may be clonally propagated in culture, to continuously produce hepatocytes and cholangiocytes as descendants while maintaining primitive stem cells. When expanded cells are transplanted into recipient animals, they morphologically and functionally differentiated into hepatocytes and cholangiocytes, with reconstitution of hepatocyte and bile duct structures. Furthermore, these cells differentiated into pancreatic ductal and acinar cells or intestinal epithelial cells when transplanted into pancreas or duodenal wall. Thus, the self-renewing multipotent stem cells persist in the developing mouse liver and can be induced to become cells of other organs of endodermal origin under appropriate microenvironment, providing new insight into therapies for diseases of the digestive system.

    摘要翻译： 本发明使用流式细胞术和体外基于单细胞的测定法提供克隆多能肝干细胞。 这些细胞具有多谱分化潜能和自我更新能力。 这些细胞可以在培养物中克隆繁殖，以连续产生肝细胞和胆管细胞作为后代，同时保持原始干细胞。 当将扩增的细胞移植到受体动物中时，其形态和功能上分化为肝细胞和胆管细胞，重组肝细胞和胆管结构。 此外，当移植到胰腺或十二指肠壁时，这些细胞分化为胰腺导管和腺泡细胞或肠上皮细胞。 因此，自我更新的多能干细胞持续存在于发育中的小鼠肝脏中，并可在适当的微环境下诱导成为内胚层起源的其他器官的细胞，为消化系统疾病的治疗提供新的见解。

    Method for producing differentiated cells
    6.
    发明授权
    Method for producing differentiated cells 有权
    产生分化细胞的方法

    公开(公告)号：US09200254B2

    公开(公告)日：2015-12-01

    申请号：US13496321

    申请日：2010-09-15

    申请人： Koji Eto ,  Naoya Takayama ,  Sou Nakamura ,  Hiromitsu Nakauchi

    发明人： Koji Eto ,  Naoya Takayama ,  Sou Nakamura ,  Hiromitsu Nakauchi

    IPC分类号： C12N5/00 ,  C12N5/02 ,  C12N5/078 ,  A61K35/00

    CPC分类号： C12N5/0641 ,  A61K35/00 ,  C12N5/0644 ,  C12N2501/40 ,  C12N2501/48 ,  C12N2501/60 ,  C12N2501/606 ,  C12N2506/02 ,  C12N2506/45

    摘要： The present invention has an object of providing a method for producing specific cells by amplifying cells in a desired differentiation stage. The present invention provides a method for producing specific cells by inducing differentiation of cells, wherein an oncogene is forcibly expressed in cells in a desired differentiation stage to amplify the cells in the desired differentiation stage. The present invention also provides a method for producing specific cells, wherein oncogene-induced senescence (OIS) which is induced by the oncogene expressed in the cells in the desired differentiation stage is suppressed.

    摘要翻译： 本发明的目的是提供通过在期望的分化阶段中扩增细胞来产生特定细胞的方法。 本发明提供通过诱导细胞分化来产生特异性细胞的方法，其中癌细胞在期望的分化阶段的细胞中被强制表达以扩增所需分化阶段的细胞。 本发明还提供了一种制备特定细胞的方法，其中抑制了在所需分化阶段中在细胞中表达的癌基因诱导的致癌基因诱导的衰老（OIS）。

    Method for Producing Polyploidized Megakaryocyte and Platelets
    8.
    发明申请
    Method for Producing Polyploidized Megakaryocyte and Platelets 有权
    多倍体巨核细胞和血小板产生方法

    公开(公告)号：US20140127815A1

    公开(公告)日：2014-05-08

    申请号：US14117465

    申请日：2012-05-11

    申请人： Koji Eto ,  Hiromitsu Nakauchi ,  Naoya Takayama ,  Sou Nakamura

    发明人： Koji Eto ,  Hiromitsu Nakauchi ,  Naoya Takayama ,  Sou Nakamura

    IPC分类号： C12N5/078 ,  C12N15/85

    CPC分类号： C12N15/85 ,  A61K35/19 ,  C12N5/0644 ,  C12N2501/165 ,  C12N2501/48 ,  C12N2506/02

    摘要： An object of the present invention is to provide a method of promoting polyploidization of megakaryocytes and thereby producing highly polyploidized megakaryocytes, a method of efficiently producing platelets from polyploidized megakaryocytes, and the like. The present invention provides a method of producing polyploidized megakaryocytes comprising a step of forcing expression of an apoptosis suppressor gene in megakaryocytes before polyploidization and culturing the resulting cells.

    摘要翻译： 本发明的目的是提供一种促进巨核细胞多倍体化，从而产生高度多倍体的巨核细胞的方法，一种从多倍体巨核细胞中有效产生血小板的方法等。 本发明提供多倍体巨核细胞的制造方法，其特征在于，在多倍体化前，在巨核细胞中强制表达凋亡抑制基因的步骤，培养所得细胞。

    Novel Method for Producing Differentiated Cells
    9.
    发明申请
    Novel Method for Producing Differentiated Cells 有权
    生产分化细胞的新方法

    公开(公告)号：US20120238023A1

    公开(公告)日：2012-09-20

    申请号：US13496321

    申请日：2010-09-15

    申请人： Koji Eto ,  Naoya Takayama ,  Sou Nakamura ,  Hiromitsu Nakauchi

    发明人： Koji Eto ,  Naoya Takayama ,  Sou Nakamura ,  Hiromitsu Nakauchi

    IPC分类号： C12N15/85 ,  C12N5/10

    CPC分类号： C12N5/0641 ,  A61K35/00 ,  C12N5/0644 ,  C12N2501/40 ,  C12N2501/48 ,  C12N2501/60 ,  C12N2501/606 ,  C12N2506/02 ,  C12N2506/45

    摘要： The present invention has an object of providing a method for producing specific cells by amplifying cells in a desired differentiation stage. The present invention provides a method for producing specific cells by inducing differentiation of cells, wherein an oncogene is forcibly expressed in cells in a desired differentiation stage to amplify the cells in the desired differentiation stage. The present invention also provides a method for producing specific cells, wherein oncogene-induced senescence (OIS) which is induced by the oncogene expressed in the cells in the desired differentiation stage is suppressed.

    摘要翻译： 本发明的目的是提供通过在期望的分化阶段中扩增细胞来产生特定细胞的方法。 本发明提供通过诱导细胞分化来产生特异性细胞的方法，其中癌细胞在期望的分化阶段的细胞中被强制表达以扩增所需分化阶段的细胞。 本发明还提供了一种制备特定细胞的方法，其中抑制了在所需分化阶段中在细胞中表达的癌基因诱导的致癌基因诱导的衰老（OIS）。