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The induction cf the differentiation of human embryonic stem cells into hematopoietic stem and progenitor cells.

诱导人胚胎干细胞分化为造血干细胞和祖细胞。

基本信息

批准号：
15390321
负责人：
TSUJI Kohichiro
金额：
$ 9.47万
依托单位：
The University of Tokyo
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2004
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15390321/
关键词：
human embryonic stem cells hematopoietic stem cells hematopoietic progenitor cells blood cells transfusion medicine regenerative medicine embryonic hematopoiesis stromal cells 胎児肝 ES細胞分化誘導長期造血再構築能 NOD SCIDマウス

项目摘要

Human embryonic stem cells (ESC) recently established from the inner cell mass of human preimplantation embryos have the abilities to be maintained as undifferentiated cells in culture without apparent limit and to differentiate into all types of tissue cells. This property of human ESC indicates the potential application for blood medicine including cellular therapies, such as blood transfusion and hematopoietic stem cell transplantation, and the evaluation of drug effect on various blood cells in vitro.Because hematopoietic tissues play crucial roles in survival, differentiation and proliferation of hematopoietic cells, it is important to reproduce the circumstance surrounding hematopoietic cells in vitro for their development. In embryo, the development of hemotopoietic system is a complex process which sequentially occurs in several tissues, but fetal liver (FL) is the predominant source of blood cells until just before time when the hematopoiesis resides in bone marrow.We then established stromal cells from mouse FL cells and cocultured human embryonic stem cells (ESC) with them. Human ESC began to differentiate at day 6 of coculture, and generated immature hematopoietic cells at day 12. At day 16, we performed clonal cultures of these cocultured cells for 2 weeks. The human ESC-derived cells produced a number of myeloid, erythroid and multi-lineage colonies, which consist of myeloid cells including neutrophils and macrophages, erythroid cells which contain mature erythrocytes, and both, respectively. This result indicates that human ESC have the capability to generate a variety of hematopoietic progenitors which can produce mature blood cells in coculture with mouse FL-derived stromal cells. The human ESC-derived hematopoietic progenitors can be a novel source for the cells applicable to various cellular therapies.

新近从人着床前胚胎内细胞团中分离出的人胚胎干细胞具有在体外无明显限制地保持未分化细胞的能力，并能分化为各种类型的组织细胞。人胚胎干细胞的这一特性预示着其在包括细胞治疗在内的血液医学中的潜在应用，如输血和造血干细胞移植，以及在体外评价药物对各种血细胞的作用。由于造血组织在造血细胞的生存、分化和增殖中起着至关重要的作用，因此在体外复制造血细胞周围的环境对其发育至关重要。在胚胎中，造血系统的发育是一个复杂的过程，它依次发生在多个组织中，而胎肝(FL)一直是血细胞的主要来源，直到造血停留在骨髓中。人ESC在共培养第6天开始分化，第12天产生未成熟的造血细胞。在第16天，我们对这些细胞进行克隆培养2周。人胚胎干细胞产生了大量的髓系、红系和多系集落，其中髓系细胞包括中性粒细胞和巨噬细胞，红系细胞包括成熟的红细胞，两者都有。这一结果表明，人胚胎干细胞有能力在与小鼠FL来源的基质细胞共培养中产生多种造血祖细胞，这些造血祖细胞可以产生成熟的血细胞。人胚胎干细胞来源的造血祖细胞可能是一种新的细胞来源，适用于各种细胞疗法。