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.

最近从人类前植入前胚胎的内部细胞质量建立的人类胚胎干细胞（ESC）具有在培养中保持不分化的细胞而没有明显限制的能力，并且可以区分所有类型的组织细胞。人类ESC的这种特性表明了血液医学的潜在应用，包括细胞疗法，例如输血和造血干细胞移植，以及对药物对各种血液细胞的影响的评估。造血组织在生存，分化，造血细胞的分化和增殖中至关重要的造血性细胞在源源不断的情况下，对源化的造成范围的开发，这些脑部的发展是源化的。在胚胎中，血压素系统的发展是一个复杂的过程，依次发生在几个组织中，但是胎儿肝脏（FL）是血细胞的主要来源，直到造血性造血骨髓属于骨髓的时间之前，我们随后在骨髓中驻留在小鼠FL细胞中的基质细胞，并通过其胚胎胚胎胚胎（逃生）与之灭。人类ESC在共培养的第6天开始分化，并在第12天产生了未成熟的造血细胞。在第16天，我们对这些共培养细胞进行了克隆培养2周。人类ESC衍生的细胞产生了许多髓样细胞，红系和多细胞菌落，这些菌落由髓样细胞组成，包括中性粒细胞和巨噬细胞，含有成熟的红细胞的红细胞细胞，以及两者。该结果表明，人ESC具有产生各种造血祖细胞的能力，这些祖细胞可以用小鼠FL衍生的基质细胞在共培养中产生成熟的血细胞。人类ESC衍生的造血祖细胞可能是适用于各种细胞疗法的细胞的新来源。