Regulation of human megakaryocytopoiesis. An in vito analysis.

Regulation of human megakaryocytopoiesis. An in vito analysis.
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人类巨核细胞生成的调节。

DOI:
10.1172/jci110309
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发表时间:
1981
期刊:
The Journal of clinical investigation
影响因子:
--
通讯作者:
Bruno,E
Bruno,E
中科院分区:
--
文献类型:
--
作者:
Mazur,EM;Hoffman,R;Bruno,E

文献摘要

被引文献

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我们最近描述了一种测定系统,用于人外周血巨核细胞集落形成单位细胞(CFU-M)使用抗血小板糖蛋白抗血清探针,以确定巨核细胞集落在体外生长。应用该系统研究了人骨髓CFU-M的性质和调控。在不存在特异性巨核细胞生长促进因子的情况下,每培养5 × 10(5)个细胞克隆12.4 +/- 3.0(平均值+/- SEM)个巨核细胞集落。在孵育6天后出现菌落,在第10天和第14天之间达到峰值,此后缓慢下降。促红细胞生成素浓度高达4 U/ml未能增加菌落数。含有爆发促进活性和集落刺激活性的培养基也不能提高巨核细胞集落接种效率。先前已证实含有血小板生成素的人胚肾细胞条件培养基对巨核细胞集落数也没有影响。与此相反,从三个严重再生障碍性贫血患者的血清产生显着增强CFU-M衍生的集落形成在体外。巨核细胞集落的数量和每个集落的巨核细胞数量均与再生障碍性贫血血清的最终浓度成比例增加。在存在10%再生障碍性贫血血清的情况下,培养的巨核细胞集落数与接种的骨髓单核细胞数呈线性关系,表明每个集落的克隆来源。骨髓CFU-M的体外测定是研究人巨核细胞生成调控的可靠方法。最初的数据表明,巨核细胞的产生是由再生障碍性贫血血清中可检测到的一种因子刺激的,这种因子可能与其他已知的造血干细胞调节因子不同。图片
We have recently described an assay system for human peripheral blood megakaryocyte colony-forming unit cells (CFU-M) using an anti-platelet glycoprotein antiserum probe to define megakaryocyte colonies grown in vitro. This system was applied to study the nature and regulation of human bone marrow CFU-M. In the absence of a specific megakaryocyte growth-promoting factor, 12.4 +/- 3.0 (means +/- SEM) megakaryocyte colonies were cloned per 5 X 10(5) cells cultured. Colonies were present after 6 d of incubation reaching peak numbers between days 10 and 14 and slowly decreasing thereafter. Erythropoietin in concentrations of up to 4 U/ml failed to augment colony numbers. Also failing to enhance megakaryocyte colony plating efficiency were media containing burst-promoting activity and colony-stimulating activity. A medium conditioned by human embryonic kidney cells, which has been previously demonstrated to contain thrombopoietin, also had no effect on megakaryocyte colony numbers. In contrast, sera from three patients with severe aplastic anemia produced significant enhancement of CFU-M-derived colony formation in vitro. Both the number of megakaryocyte colonies present and the number of megakaryocytes per colony were increased in proportion to the final concentration of aplastic anemia serum. In the presence of 10% aplastic anemia serum, cultured megakaryocyte colony numbers were linear with respect to the number of bone marrow mononuclear cells plated suggesting a clonal origin of each of the colonies. This in vitro assay for bone marrow CFU-M is a reliable means by which to study the regulation of human megakaryocytopoiesis. Initial data suggest that megakaryocyte production is stimulated by a factor detectable in aplastic anemia serum that may be distinct from other known hematopoietic stem cell regulators.Images