Human circulating CD14+ monocytes as a source of progenitors that exhibit mesenchymal cell differentiation
Human circulating CD14+ monocytes as a source of progenitors that exhibit mesenchymal cell differentiation
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DOI：
10.1189/jlb.0403170
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发表时间：
2003-11-01
影响因子：
5.5
通讯作者：
Ikeda, Y
中科院分区：
文献类型：
--
作者：
Kuwana, M;Okazaki, Y;Ikeda, Y
循环中的CD 14（+）单核细胞是吞噬细胞的前体，如巨噬细胞和树突状细胞。在这里，我们报告原始细胞与成纤维细胞样形态来自人外周血CD 14（+）单核细胞，可以分化成几个不同的间充质细胞谱系。我们将这种细胞群命名为单核细胞衍生的间充质祖细胞（MOMP）。MOMPs在体外从人外周血单核细胞中获得，所述人外周血单核细胞在单独的胎牛血清作为生长因子来源的存在下在纤连蛋白上培养。MOMPs具有独特的分子表型-CD 14（+）CD 45（+）CD 34（+）I型胶原（+）-，并显示单核细胞、内皮细胞和间充质细胞的混合形态和分子特征。发现MOMP来源于循环CD 14（+）单核细胞的亚群，并且它们的分化需要它们结合纤连蛋白并暴露于来源于外周血CD 14（-）细胞的一种或多种可溶性因子。MOMPs可以在培养物中扩增，而不会失去其原始表型，最多可传5代。MOMPs诱导沿着多肢芽中胚层谱系分化导致成骨细胞、骨骼肌成肌细胞、软骨细胞和脂肪细胞特异性基因和蛋白质的表达。我们的发现首次证明了人类循环中的CD 14（+）单核细胞是表现出间充质细胞分化的祖细胞的来源。
Circulating CD14(+) monocytes are precursors of phagocytes, such as macrophages and dendritic cells. Here we report primitive cells with a fibroblast-like morphology derived from human peripheral blood CD14(+) monocytes that can differentiate into several distinct mesenchymal cell lineages. We named this cell population monocyte-derived mesenchymal progenitor (MOMP). MOMPs were obtained in vitro from human peripheral blood mononuclear cells cultured on fibronectin in the presence of fetal bovine serum alone as a source of growth factors. MOMPs had a unique molecular phenotype-CD14(+)CD45(+)CD34(+) type I collagen(+)-and showed mixed morphologic and molecular features of monocytes and endothelial and mesenchymal cells. MOMPs were found to he derived from a subset of circulating CD14(+) monocytes, and their differentiation required that they bind fibronectin and be exposed to one or more soluble factors derived from peripheral blood CD14(-) cells. MOMPs could be expanded in culture without losing their original phenotype for up to five passages. The induction of MOMPs to differentiate along multiple limb-bud mesodermal lineages resulted in the expression of genes and proteins specific for osteoblasts, skeletal myoblasts, chondrocytes, and adipocytes. Our findings represent the first evidence that human circulating CD14(+) monocytes are a source of progenitors that exhibit mesenchymal cell differentiation.