Human circulating CD14+ monocytes as a source of progenitors that exhibit mesenchymal cell differentiation

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  • Masataka Kuwana
    Institute for Advanced Medical Research, Keio University School of Medicine , Tokyo , Japan
  • Yuka Okazaki
    Institute for Advanced Medical Research, Keio University School of Medicine , Tokyo , Japan
  • Hiroaki Kodama
    Department of Internal Medicine, Keio University School of Medicine , Tokyo , Japan
  • Keisuke Izumi
    Institute for Advanced Medical Research, Keio University School of Medicine , Tokyo , Japan
  • Hidekata Yasuoka
    Institute for Advanced Medical Research, Keio University School of Medicine , Tokyo , Japan
  • Yoko Ogawa
    Institute for Advanced Medical Research, Keio University School of Medicine , Tokyo , Japan
  • Yutaka Kawakami
    Institute for Advanced Medical Research, Keio University School of Medicine , Tokyo , Japan
  • Yasuo Ikeda
    Department of Internal Medicine, Keio University School of Medicine , Tokyo , Japan

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<jats:title>Abstract</jats:title> <jats:p>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 be 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.</jats:p>

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