CD105-Positive Cells in Pulmonary Arterial Blood of Adult Human Lung Cancer Patients Include Mesenchymal Progenitors

CD105-Positive Cells in Pulmonary Arterial Blood of Adult Human Lung Cancer Patients Include Mesenchymal Progenitors
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DOI:
10.1634/stemcells.2008-0037
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发表时间:
2008-01-01
期刊:
影响因子:
5.2
通讯作者:
Ochiai, Atsushi
Ochiai, Atsushi
中科院分区:
医学2区
文献类型:
--
作者:
Chiba, Haruki;Ishii, Genicihro;Ochiai, Atsushi

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间充质祖细胞(MPCs)具有成纤维细胞样形态,是能够分化为各种间充质组织的多能细胞。尽管在成人骨髓和脐带血中发现了MPCs,但对于MPCs是否存在于成人血液中仍存在争议。为了确定它们是否是,我们培养了来自肺癌患者肺动脉血的单核细胞(MNCs)。在94%(31例中的29例)的情况下,成纤维细胞体外扩增并分化成骨谱系或成脂谱系,这取决于所使用的特定诱导培养基。这些结果表明,在肺癌附近的肺动脉血(PA)中含有MPC(PA-MPC)。用分层分类算法对PA-MPC、骨髓来源的MPC(BM-MPC)和肺组织来源的成纤维细胞的cDNA谱进行聚类。PA-MPCs(3例)和BM-MPCs的表达谱与组织来源的成纤维细胞的表达谱明显分离,并且来自两名患者的PA-MPCs的表达谱与BM-MPCs的表达谱分离。为了鉴定PA-MPC的来源,将来自肺动脉血的MNC暴露于抗CD 14、抗CD 105、抗CD 3和抗CD 20抗体。8/8例(100%)CD 105(+)单核细胞生成MPC,而5/3例(60%)、2/5例(40%)和0/3例(0%)的CD 14(+)、CD 3(+)和CD 20(+)单核细胞生成MPC。这些发现首次明确证明了成人肺癌患者肺动脉血中的CD 105(+)MNC部分包括MPC。干细胞2008; 26:2523-2530
Mesenchymal progenitor cells (MPCs) exhibit fibroblast-like morphology and are multipotent cells capable of differentiating into various mesenchymal tissues. Although MPCs have been found in adult bone marrow and umbilical cord blood, there is still controversy as to whether the MPCs are present in adult human blood. To determine whether they are, we cultured mononuclear cells (MNCs) from the pulmonary arterial blood of lung cancer patients. In 94% (29 of 31) of the cases, fibroblasts were expanded ex vivo and were differentiated into an osteogenic lineage or an adipogenic lineage, depending on the specific inducing medium used. These results indicated that pulmonary arterial blood (PA) in the vicinity of lung cancers contains MPCs (PA-MPCs). The cDNA profiles of PA-MPCs, MPCs derived from bone marrow (BM-MPCs), and lung tissue-derived fibroblasts were clustered with a hierarchical classification algorithm. The expression profiles of PA-MPCs (three cases) and BM-MPCs were clearly separated from those of the tissue-derived fibroblasts, and the profiles of the PA-MPCs from the two patients were separated from those of the BM-MPCs. To identify the source of the PA-MPCs, the MNCs from pulmonary arterial blood were exposed to anti-CD14, anti-CD105, anti-CD3, and anti-CD20 antibodies. CD105(+) MNCs generated MPCs in eight of eight cases (100%), whereas CD14(+), CD3(+), and CD20(+) mononuclear cells generated MPCs in three of five cases (60%), two of five cases (40%), and zero of three cases (0%), respectively. These findings are the first clear proof that the CD105(+) MNC fraction in the pulmonary arterial blood of adult lung cancer patients includes MPCs. STEM CELLS 2008; 26: 2523-2530