公开(公告)号：US20110231944A1

公开(公告)日：2011-09-22

申请号：US13062439

申请日：2009-09-04

申请人： Hiroshi Watarai ,  Tomokatsu Ikawa ,  Fumihiko Ishikawa ,  Hiroshi Kawamoto ,  Haruhiko Koseki ,  Masaru Taniguchi

发明人： Hiroshi Watarai ,  Tomokatsu Ikawa ,  Fumihiko Ishikawa ,  Hiroshi Kawamoto ,  Haruhiko Koseki ,  Masaru Taniguchi

IPC分类号： A01K67/027 ,  C12N5/071 ,  C12N5/10 ,  C12P21/08 ,  C12N15/00

CPC分类号： C12N5/0696 ,  A01K2267/01 ,  C12N15/8775 ,  C12N2501/2302 ,  C12N2501/235 ,  C12N2501/602 ,  C12N2501/603 ,  C12N2501/604 ,  C12N2501/606 ,  C12N2506/11 ,  C12N2510/00

摘要： Provided are a B cell-derived iPS cell generated using a convenient technique, a technology for providing a human antibody at low cost using the iPS cell, an immunologically humanized mouse prepared using cells differentiated from the iPS cell, and the like. Also provided are a cloned cell obtained by contacting a B cell with nuclear reprogramming factors excluding C/EBPα and Pax5 expression inhibiting substances, particularly nucleic acids that encode Oct3/4, Sox2, Klf4 and c-Myc, wherein the cloned cell has an immunoglobulin gene rearranged therein and possesses pluripotency and replication competence (B-iPS cell). Still also provided are a method of producing a monoclonal antibody against a specified antigen, comprising recovering an antibody from a culture of B cells obtained by differentiating a B-iPS cell derived from a B cell immunized with the specified antigen, and a method of generating an immunologically humanized mouse, comprising transplanting to an immunodeficient mouse a human immunohematological system cell obtained by differentiating a B-iPS cell.

摘要翻译： 提供了使用方便的技术产生的B细胞衍生的iPS细胞，使用iPS细胞以低成本提供人抗体的技术，使用从iPS细胞分化的细胞制备的免疫人源化小鼠等的技术。 还提供了通过使B细胞与不包括C /EBPα和Pax5表达抑制物质，特别是编码Oct3 / 4，Sox2，Klf4和c-Myc的核酸的核重编程因子接触获得的克隆细胞，其中克隆的细胞具有免疫球蛋白 基因重排并具有多能性和复制能力（B-iPS细胞）。 还提供了针对特定抗原产生单克隆抗体的方法，包括从通过分化来源于用特定抗原免疫的B细胞的B-iPS细胞获得的B细胞的培养物中回收抗体，以及产生 一种免疫人源化的小鼠，包括将免疫缺陷小鼠移植到通过分化B-iPS细胞获得的人免疫血液学系统细胞中。

公开(公告)号：US20110158955A1

公开(公告)日：2011-06-30

申请号：US12922037

申请日：2009-03-11

申请人： Yoshimoto Katsura ,  Hiroshi Kawamoto ,  Tomokatsu Ikawa

发明人： Yoshimoto Katsura ,  Hiroshi Kawamoto ,  Tomokatsu Ikawa

IPC分类号： A61K35/12 ,  C12N5/0789 ,  C12N5/078 ,  A61P37/02

CPC分类号： C12N5/0647 ,  A61K2035/124 ,  C12N2501/60 ,  C12N2501/999 ,  C12N2506/11

摘要： Provided are a new method of producing cells having characteristics of hematopoietic stem/progenitor cells, for use in hematopoietic stem cell transplantation, and hematopoietic stem/progenitor cell-like cells produced by the method. Provided in particular are a method of producing hematopoietic stem/progenitor cell-like cells retaining differentiation pluripotency and self-replication potential, comprising (1) a step for providing a mammalian pro-B cell or progenitor cell thereof, and (2) a step for culturing the cell (1) above under conditions for induction of differentiation into B cells, wherein the function and/or expression of the transcription factor E2A is suppressed at least at the stage of pre-pro-B cells or pro-B cells in the process (2) above; a hematopoietic stem/progenitor cell-like cell produced by the method; and an immunotherapeutic agent comprising the hematopoietic stem/progenitor cell-like cell, and the like.

摘要翻译： 本发明提供了一种生产造血干/细胞移植造血干/祖细胞特征的细胞的新方法，以及通过该方法产生的造血干/祖细胞样细胞。 特别提供一种产生保留分化多能性和自我复制潜力的造血干/祖细胞样细胞的方法，其包括（1）提供哺乳动物前体B细胞或祖细胞的步骤，和（2）步骤 用于在诱导分化成B细胞的条件下培养上述细胞（1），其中转录因子E2A的功能和/或表达至少在前B细胞或前B细胞的阶段被抑制 上述过程（2）; 通过该方法产生的造血干/祖细胞样细胞; 和包含造血干/祖细胞样细胞的免疫治疗剂等。