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Purification and ampliefication of hematopoietic stem cells

造血干细胞的纯化和扩增

基本信息

批准号：
06277104
负责人：
SUDA Toshio
金额：
$ 128.83万
依托单位：
Kumamoto University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research on Priority Areas
财政年份：
1994
资助国家：
日本
起止时间：
1994 至 1998
项目状态：
已结题

项目摘要

Soda, Miura and Kanakura have shown that some signal transduction pathways in hemopoictic stem cells (HSC). Novel receptor tyrosine kinases such as TIEs, HTK and STK/RON were cloned from purified HSC by RT-PCR and especially TIE-1 and 2 are expressed in hematopotetic stem cells as well as in vascular endothelial cells From these findings, it becomes possible to analyze the development of hematopoietic stem cells from angioblasts, which are endothelial precursor cells. It was clarified that gain of function of c Kit caused the autonomous proliferation of hematopoietic cells (mast cells) and specified cells in the gut (Kajal cells).Nakauchi has demonstrated that CD34tィイD1+ィエD1KitィイD1+ィエD1ScaィイD1+ィエD1LinィイD1-ィエD1 and CD34ィイD1+ィエD1KitィイD1+ィエD1ScaィイD1+ィエD1LinィイD1-ィエD1 cells of adult murine bone marrow have been shown to contain long-and short-term repopulating hematopoictic stem cells by a transplantation assay. CD34 negative stein cells are also confirmed in human hematopoletic system. There has been great interest in the ex vivo expansion of human hemopoictic stem/progenitor cells for clinical applications. Nakahata has shown that heanatopoietic progenitor cellscan be expanded in the presence of soluble IL-6 receptor+IL-6+SCF. However. stein cell expansion is still insatisfactoiy. Asano has tried to establish monkey transplantation system to analyze the hurtan HSC.Yamamoto has clearly shown that GATA and Maf families am involved in erythropoiesis by the GATA-1 KO mice and GATA promoter-LacZ transgenic mice.

Soda， Miura和Kanakura已经证明了造血干细胞（HSC）中的一些信号转导途径。通过RT-PCR从纯化的HSC中克隆出新的酪氨酸受体激酶，如TIEs、HTK和STK/RON，特别是TIE-1和2在造血干细胞和血管内皮细胞中表达。这些发现使得分析造血干细胞从内皮前体细胞成血管细胞发育成为可能。阐明了c Kit功能的获得可引起造血细胞（肥大细胞）和肠道特定细胞（Kajal细胞）的自主增殖。Nakauchi通过移植实验证明，成年小鼠骨髓中的CD34t γ γ γ γ γ + γ γ γ γ + γ γ γ + γ γ γ + γ γ γ + γ γ + γ γ + γ γ + γ γ + γ γ + γ γ + γ γ + γ γ + γ γ + γ γ + γ γ + γ γ + γ γ + γ γ + γ γ + γ γ + γ γ + γ γ + γ γ + γ γ + γ γ + γ γ + γ γ + γ γ + γ γ + γ γ + γ γ + γ γ + γ γ + γ γ + γ γ + γ γ + γ γ γ - γ γ - γ γ - γ γ细胞含有长期和短期再生造血干细胞。CD34阴性的stein细胞也在人造血系统中得到证实。人类造血干细胞/祖细胞的体外扩增用于临床应用已经引起了人们极大的兴趣。Nakahata已经证明造血祖细胞在可溶性IL-6受体+IL-6+SCF存在下可以扩增。然而。斯坦因细胞扩增仍不令人满意。浅野试图建立猴子移植系统来分析人体造血干细胞。Yamamoto清楚地表明GATA和Maf家族参与了GATA-1 KO小鼠和GATA启动子- lacz转基因小鼠的红细胞生成。