Two distinct stem cell lineages in murine bone marrow

Two distinct stem cell lineages in murine bone marrow
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DOI:
10.1634/stemcells.2006-0325
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发表时间:
2007-01-01
期刊:
影响因子:
5.2
通讯作者:
Matsuzaki, Yumi
Matsuzaki, Yumi
中科院分区:
医学2区
文献类型:
--
作者:
Koide, Yoko;Morikawa, Satoru;Matsuzaki, Yumi

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间充质干细胞(MSC)是一种独特类型的成体干细胞,易于在离体培养中分离、培养和操作。这些细胞具有很大的可塑性和治疗应用的潜力,但由于其频率低,缺乏对细胞表面标志物及其起源位置的了解,因此对其特性知之甚少。本研究的目的是解决造血干细胞和间充质干细胞的谱系关系不明确。将遗传标记的高度纯化的造血干细胞(HSC)移植到野生型动物中,并且在骨髓再增殖后,通过分析体外分化成间充质组织来严格研究后代分化成间充质组织的潜力。没有/很少的造血细胞有助于集落形成单位成纤维细胞活性和间充质细胞分化;然而,未分级的骨髓细胞不仅导致造血细胞的广泛替代,而且还导致间充质细胞,包括MSC。因此,我们的结论是,纯化的HSC没有显着的潜能分化为间充质谱系。这些数据有力地表明,造血细胞和间充质谱系细胞来源于个体谱系特异性干细胞。此外,我们成功地可视化间充质谱系细胞在体内显微成像和免疫组织化学。流式细胞术分析显示CD 140 b(PDGFR β)可能是间充质谱系细胞的特异性标志物。这些结果可能会加强对间充质干细胞身份和特征的更全面看法的迫切需要。
Mesenchymal stem cells (MSC), a distinct type of adult stem cell, are easy to isolate, culture, and manipulate in ex vivo culture. These cells have great plasticity and potential for therapeutic application, but their properties are poorly understood because of their low frequency and the lack of knowledge on cell surface markers and their location of origin. The present study was designed to address the undefined lineage relationship of hematopoietic and mesenchymal stem cells. Genetically marked, highly purified hematopoietic stem cells (HSCs) were transplanted into wild-type animals and, after bone marrow repopulation, the progeny were rigorously investigated for differentiation potential into mesenchymal tissues by analyzing in vitro differentiation into mesenchymal tissues. None/very little of the hematopoietic cells contributed to colony-forming units fibroblast activity and mesenchymal cell differentiation; however, unfractionated bone marrow cells resulted in extensive replacement of not only hematopoietic cells but also mesenchymal cells, including MSCs. As a result, we concluded that purified HSCs have no significant potency to differentiate into mesenchymal lineage. The data strongly suggest that hematopoietic cells and mesenchymal lineage cells are derived from individual lineage-specific stem cells. In addition, we succeeded in visualizing mesenchymal lineage cells using in vivo microimaging and immunohistochemistry. Flow cytometric analysis revealed CD140b (PDGFR beta) could be a specific marker for mesenchymal lineage cells. The results may reinforce the urgent need for a more comprehensive view of the mesenchymal stem cell identity and characteristics.