Analysis of the molecular mechanism regulating the development of hematopoietic stem cells in cord blood and their application to ex vivo expansion
脐带血造血干细胞发育调控分子机制分析及其在离体扩增中的应用
基本信息
- 批准号:10470174
- 负责人:
- 金额:$ 3.46万
- 依托单位:
- 依托单位国家:日本
- 项目类别:Grant-in-Aid for Scientific Research (B).
- 财政年份:1998
- 资助国家:日本
- 起止时间:1998 至 2000
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
We demonstrated a significant ex vivo expansion of cord blood hematopoietic stem cells capable of repopulating in NOD/SCID mice, using a combination of stem cell factor (SCF), Flk2/Flt3 ligand (FL), thrombopoietin (TPO) and a complex of interleukin (IL)-6 and soluble IL-6 receptor (IL-6/sIL-6R). When 1 to 2x104 cord blood CD34+ cells and the cells cultured with SCF+FL, SCF+FL+TPO and SCF+FL+TPO+IL-6/sIL-6R for 7 days were transplanted into NOD/SCID mice, 6/25 (24%), 7/16 (44%), 7/14 (50%) and 13/16 (81%) recipients revealed successful engraftment, and the bone marrow cells of the engrafted recipients contained 1.4%, 2.3%, 6.7% and 11.5% of human CD45+ cells, respectively, 10 to 12 weeks after the transplantation. The CD45+ cells in the recipients engrafted with the cells cultured with SCF+FL+TPO+IL-6/sIL-6R consisted of various lineages and a large number of CD34+ cells, which formed human hematopoietic colonies in in vitro clonal culture. In comparion of the reconstitution between fresh CD34+ cells from 12 samples and their progenies cultured with SCF+FL+TPO+IL-6/sIL-6R, the proportion of CD45+ cells in recipient marrow was 10 times higher in the latter, indicating the significant expansion of the long-term repopulating hematopoietic stem cells. The expansion rate was estimated at 4.2-fold by a limiting dilution method. The addition of IL-3 to the cytokine combination abrogated the repopulating ability of the expanded cells. The present study may provide a novel culture method for the expansion of human transplantable hematopoietic stem cells aimed for clinical applications.
我们证明了使用干细胞因子 (SCF)、Flk2/Flt3 配体 (FL)、血小板生成素 (TPO) 和白细胞介素复合物的组合,能够在 NOD/SCID 小鼠中重新增殖的脐带血造血干细胞的显着离体扩增(IL)-6 和可溶性 IL-6 受体 (IL-6/sIL-6R)。当1至2x104个脐带血CD34+细胞以及与SCF+FL、SCF+FL+TPO和SCF+FL+TPO+IL-6/sIL-6R培养7天的细胞移植到NOD/SCID小鼠中时,6/25 (24%)、7/16 (44%)、7/14 (50%) 和 13/16 (81%) 收件人显示成功移植后 10 至 12 周,移植受者的骨髓细胞中分别含有 1.4%、2.3%、6.7% 和 11.5% 的人 CD45+ 细胞。 SCF+FL+TPO+IL-6/sIL-6R培养细胞移植后的受者体内CD45+细胞谱系多样,并含有大量CD34+细胞,在体外克隆培养中形成人造血集落。 12个样本的新鲜CD34+细胞与其用SCF+FL+TPO+IL-6/sIL-6R培养的子代的重建比较,后者受者骨髓中CD45+细胞的比例高出10倍,表明显着长期再生造血干细胞的扩增。通过有限稀释法估计膨胀率为4.2倍。将IL-3添加到细胞因子组合中会消除扩增细胞的再增殖能力。本研究为临床应用的人类可移植造血干细胞的扩增提供了一种新的培养方法。
项目成果
期刊论文数量(279)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
田中竜平: "造血器疾患治療マニュアル"メディカルレビュー社(大阪)(印刷中).
田中龙平:《造血系统疾病治疗手册》Medical Review Co., Ltd.(大阪)(出版中)。
- DOI:
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- 影响因子:0
- 作者:
- 通讯作者:
Tsuji K.: "Methods in Molecular Medicine-Cytokines and Colony Stimulating Factors"The Human Press (in press).
Tsuji K.:“分子医学方法——细胞因子和集落刺激因子”The Human Press(出版中)。
- DOI:
- 发表时间:
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- 影响因子:0
- 作者:
- 通讯作者:
Ebihara Y.: "Exclusive expression of G-CSF receptor on myeloid progenitors in bone marrow CD34^+ cells."Br.J.Haematol.. 109. 153-161 (2000)
Ebihara Y.:“骨髓 CD34^ 细胞中骨髓祖细胞上 G-CSF 受体的独家表达。”Br.J.Haematol.. 109. 153-161 (2000)
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TSUJI Kohichiro其他文献
TSUJI Kohichiro的其他文献
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{{ truncateString('TSUJI Kohichiro', 18)}}的其他基金
Investigation into the molecular mechanisms for the occurrence of leukemia using iPS cells derived from congenital bone marrow failure syndrome and establishment of the methods to prevent its occurrence
利用先天性骨髓衰竭综合征来源的iPS细胞研究白血病发生的分子机制并建立预防其发生的方法
- 批准号:
24659489 - 财政年份:2012
- 资助金额:
$ 3.46万 - 项目类别:
Grant-in-Aid for Challenging Exploratory Research
Analysis of human fetal hematopoiesis using human ES cells
使用人类 ES 细胞分析人类胎儿造血功能
- 批准号:
23659533 - 财政年份:2011
- 资助金额:
$ 3.46万 - 项目类别:
Grant-in-Aid for Challenging Exploratory Research
Establishment of a method inducing embryonic stem cells to differentiate to hematopoietic stem cells (HSC) for therapeutic HSC transplantation
诱导胚胎干细胞分化为造血干细胞(HSC)用于治疗性HSC移植的方法的建立
- 批准号:
20390291 - 财政年份:2008
- 资助金额:
$ 3.46万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Generation of transplantable hematopoietic stem cells based from human embryonic stem cells
基于人类胚胎干细胞产生可移植造血干细胞
- 批准号:
17390297 - 财政年份:2005
- 资助金额:
$ 3.46万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
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。
- 批准号:
15390321 - 财政年份:2003
- 资助金额:
$ 3.46万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Induction of differentiation of monkey embryonic stem cells into tissue-specific functional cells
猴胚胎干细胞诱导分化为组织特异性功能细胞
- 批准号:
12557067 - 财政年份:2000
- 资助金额:
$ 3.46万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
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