Koide Yoko, Morikawa Satoru, Mabuchi Yo, Muguruma Yukari, Hiratsu Emi, Hasegawa Kohji, Kobayashi Makoto, Ando Kiyoshi, Kinjo Kentaro, Okano Hideyuki, Matsuzaki Yumi
Department of Physiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
Stem Cells. 2007 May;25(5):1213-21. doi: 10.1634/stemcells.2006-0325. Epub 2007 Jan 11.
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 (PDGFRbeta) 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. Disclosure of potential conflicts of interest is found at the end of this article.
间充质干细胞（MSC）是一种独特类型的成体干细胞，易于在体外培养中分离、培养和操控。这些细胞具有很大的可塑性和治疗应用潜力，但由于其频率低以及对细胞表面标志物及其起源位置缺乏了解，它们的特性尚未得到充分认识。本研究旨在解决造血干细胞和间充质干细胞未明确的谱系关系。将经过基因标记的高度纯化造血干细胞（HSC）移植到野生型动物体内，在骨髓重建后，通过分析体外向间充质组织的分化，严格研究其后代向间充质组织的分化潜力。造血细胞中无/极少有细胞对成纤维细胞集落形成单位活性和间充质细胞分化有贡献；然而，未分离的骨髓细胞不仅导致造血细胞被大量替代，还导致包括间充质干细胞在内的间充质细胞被大量替代。因此，我们得出结论，纯化的造血干细胞向间充质谱系分化的能力不显著。这些数据强烈表明造血细胞和间充质谱系细胞源自个体谱系特异性干细胞。此外，我们通过体内显微成像和免疫组织化学成功实现了对间充质谱系细胞的可视化。流式细胞术分析显示CD140b（血小板衍生生长因子受体β）可能是间充质谱系细胞的特异性标志物。这些结果可能强化了对间充质干细胞身份和特征形成更全面认识的迫切需求。潜在利益冲突的披露见本文末尾。
