Experimental model for the development of the artificial bone marrow

人工骨髓发育的实验模型

• 批准号: 08670041
• 负责人: AIZAWA Shin
• 金额: $ 0.96万
• 依托单位: Nihon University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08670041/
• 关键词: bone marrow stromal cell; hematopoietic stem cell; adherent molecule; artificial bone marrow; hematopoietic microenvironment; cytokine; CD34; long-term bone marrow culture; ストローマ細胞

The bone marrow microenvironment has been suggested to play a important role in hematopoietic phenomenon. Stromal cells has been emphasized to be a essential component of this microenvironment, however, the complexity of the stromal cell populations makes it difficult to study the nature of their interaction with hematopoietic cells. To elucidate the hematopoietic supportive function of stromal cells, cloned stromal cell line from bone marrow was eatablished and the specific character of stromal cell was analyzed.1. When purified bone marrow hematopoietic stem cells (CD34+) were cocultivated with cloned stromal cell (in vitro bone marrow cell culture system ; LTMC system), CD34+cells were increased one-hundred higher than that of stromal cell free control and these cells were maintained for more than 8 weeks. Further study showed that the stromal cells support the hematopoietic stem cell proliferation and differentiation by the mechanisms of ; 1)production of soluble hematopoietic regu … More latory factors and 2)physical cell-to-cell interactions through the adherent molecules expressed on the surface of stromal cells. It was found that the production of hematopoietic factors from stromal cells was regulated by not only various cytokines but also neurotransmitters. A novel Kd35 protein, which involved in the proliferation and differentiation of hematopoietic stem cells was detected on the surface of stromal cells by cell blotting technique and a study for cloning of this protein is now on going.2. By using the LTMC system, a role of stromal cell in hematopoietic disorders was studied. First, it was clarified that vesnarinone, an oral therapeutic agent for cardiac failure, caused agranulocytosis through the impairment of the production of hematopoietic growth factors from stromal cells. Second, a lack of hematopoietic supportive function of stromal cells was found in the patients with myelodysplastic syndrome. All these findings suggest that LTMC system provides an essential tool for studying the hematopoietic phenomenon in vitro. Less

骨髓微环境在造血现象中起重要作用。基质细胞一直被强调是这种微环境的重要组成部分，然而，基质细胞群体的复杂性使得难以研究它们与造血细胞相互作用的性质。为阐明基质细胞的造血支持功能，建立了骨髓基质细胞克隆系，并对其特性进行了分析.将纯化的骨髓造血干细胞（CD_（34）+）与克隆化的基质细胞共培养（体外骨髓细胞培养系统; LTMC系统），CD_（34）+细胞比无基质细胞对照组增加100倍以上，并能维持8周以上。进一步的研究表明，基质细胞通过以下机制支持造血干细胞的增殖和分化：1）产生可溶性造血调节因子; ...更多信息 刺激因子和2）通过在基质细胞表面上表达的粘附分子的物理细胞与细胞的相互作用。研究发现，基质细胞造血因子的产生不仅受多种细胞因子的调节，而且还受神经递质的调节。结论：1.利用细胞印迹技术在基质细胞表面检测到一种新的Kd 35蛋白，该蛋白参与造血干细胞的增殖和分化，目前正在进行克隆研究.通过使用LTMC系统，研究了基质细胞在造血疾病中的作用。首先，阐明了用于心力衰竭的口服治疗剂维司力农通过损害基质细胞产生造血生长因子而引起粒细胞缺乏症。骨髓增生异常综合征患者骨髓基质细胞缺乏造血支持功能。所有这些结果表明，LTMC系统提供了一个必要的工具，在体外研究造血现象。少

项目成果

Nabeshima R., Aizawa S.et al.: "Effects of vesnarinone on the bone marrow stromal cell-dependent proliferation and differentiation of HL60 cells in vitro." Experimental Hematology. 25. 509-515 (1997)

Nabeshima R.、Aizawa S.et al.：“vesnarinone 对体外 HL60 细胞骨髓基质细胞依赖性增殖和分化的影响”。

Suzuki A., Aizawa S.et al.: "Enhance engraftment of intravenously transplanted hematopoietic stem cells into bone marrow of irradiated mice treated with AcSDKP." Experimental Hematology. 26. 79-83 (1998)

Suzuki A.、Aizawa S.et al.：“增强静脉移植造血干细胞在接受 AcSDKP 治疗的受辐射小鼠骨髓中的植入。”

Aizawa S.et al.: "In vivo stimulatory effects of neopterin on hematopoiesis." Pteridine. (in press). (1998)

Aizawa S.et al.：“新蝶呤对造血作用的体内刺激作用。”

S.Aizawa et al.: "Possible involvement of bone marrow stromal cells in agrarabocytosis caused by vesnarinone treatment." Acta Haematology. 98. 140-146 (1997)

S.Aizawa 等人：“骨髓基质细胞可能参与维纳里酮治疗引起的无细胞增多症。”

Yaguchi M., Aizawa S.et al.: "Role of bone marrow stromal cells on apoptotic change of hematopoietic cells in the patients with myelodysplastic syndrome." Rinshouketsueki. 37. 542-546 (1996)

Yaguchi M.，Aizawa S.et al.：“骨髓基质细胞对骨髓增生异常综合征患者造血细胞凋亡变化的作用”。