PDGFRα and CD51 mark human nestin+ sphere-forming mesenchymal stem cells capable of hematopoietic progenitor cell expansion.

PDGFRα and CD51 mark human nestin+ sphere-forming mesenchymal stem cells capable of hematopoietic progenitor cell expansion.
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DOI:
10.1084/jem.20122252
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发表时间:
2013-07-01
期刊:
The Journal of experimental medicine
影响因子:
--
通讯作者:
Frenette PS
Frenette PS
中科院分区:
其他
文献类型:
--
作者:
Pinho S;Lacombe J;Hanoun M;Mizoguchi T;Bruns I;Kunisaki Y;Frenette PS

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人巢蛋白+间充质干细胞亚群表达PDGFRα和CD 51,这些标志物可用于这些细胞的前瞻性分离。中间丝蛋白Nestin标记干/祖细胞群体,包括自我更新间充质干细胞(MSC),造血干细胞(HSC)生态位的主要组成部分。然而,巢蛋白的细胞内位置阻止其用于预期的活细胞分离。因此,重要的是找到特异性针对Nestin+细胞的表面标志物。在这项研究中,我们发现CD 45 − Ter 119 − CD 31 −小鼠骨髓(BM)基质细胞中PDGFRα和CD 51的表达表征了大部分Nestin+细胞,包含大多数成纤维细胞CFU,间充质球和移植后的自我更新能力。巢蛋白+细胞的PDGFRα+ CD 51+亚群也富含主要的HSC维持基因,支持小生境活性与MSC活性共分离的观点。此外,我们发现人胎儿骨髓中的PDGFRα+ CD 51+细胞代表了表达Nestin的CD 146+细胞的一小部分,并富含MSC和HSC的生态位活性。重要的是,培养的人PDGFRα+ CD 51+非粘附性间充质球可以显著扩增能够植入免疫缺陷小鼠的多能造血祖细胞。因此,这些结果表明,HSC龛之间的小鼠和人类物种是保守的,并建议高度纯化的非贴壁培养的龛细胞可能代表一个有用的新技术,培养人造血干细胞和祖细胞。
A subset of human Nestin+ mesenchymal stem cells expresses PDGFRα and CD51, and these markers can be used for prospective isolation of these cells. The intermediate filament protein Nestin labels populations of stem/progenitor cells, including self-renewing mesenchymal stem cells (MSCs), a major constituent of the hematopoietic stem cell (HSC) niche. However, the intracellular location of Nestin prevents its use for prospective live cell isolation. Hence it is important to find surface markers specific for Nestin+ cells. In this study, we show that the expression of PDGFRα and CD51 among CD45− Ter119− CD31− mouse bone marrow (BM) stromal cells characterizes a large fraction of Nestin+ cells, containing most fibroblastic CFUs, mesenspheres, and self-renewal capacity after transplantation. The PDGFRα+ CD51+ subset of Nestin+ cells is also enriched in major HSC maintenance genes, supporting the notion that niche activity co-segregates with MSC activity. Furthermore, we show that PDGFRα+ CD51+ cells in the human fetal BM represent a small subset of CD146+ cells expressing Nestin and enriched for MSC and HSC niche activities. Importantly, cultured human PDGFRα+ CD51+ nonadherent mesenspheres can significantly expand multipotent hematopoietic progenitors able to engraft immunodeficient mice. These results thus indicate that the HSC niche is conserved between the murine and human species and suggest that highly purified nonadherent cultures of niche cells may represent a useful novel technology to culture human hematopoietic stem and progenitor cells.
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