Human circulating CD14+ monocytes as a source of progenitors that exhibit mesenchymal cell differentiation.
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.
Kuwana
Masataka
M
Instiute for Advanced Medical Research, Keio University School of Medicine, Tokyo, Japan. kuwanam@sc.itc.keio.ac.jp
Okazaki
Yuka
Y
Kodama
Hiroaki
H
Izumi
Keisuke
K
Yasuoka
Hidekata
H
Ogawa
Yoko
Y
Kawakami
Yutaka
Y
Ikeda
Yasuo
Y
D000469:Alkaline Phosphatase / Q000097:blood; D001374:Azacitidine / Q000494:pharmacology; D001483:Base Sequence; D002118:Calcium / Q000097:blood; D002448:Cell Adhesion / Q000187:drug effects; D002454:Cell Differentiation; D002478:Cells, Cultured; D017931:DNA Primers; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000276:immunology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000276:immunology; D018950:Lipopolysaccharide Receptors / Q000097:blood* / Q000235:genetics; D008077:Lipoproteins, LDL / Q000097:blood; D008264:Macrophages / Q000166:cytology / Q000276:immunology; D008648:Mesoderm / Q000166:cytology* / Q000276:immunology; D009000:Monocytes / Q000166:cytology / Q000276:immunology*; D010012:Osteogenesis / Q000187:drug effects / Q000502:physiology; D016133:Polymerase Chain Reaction
D017931:DNA Primers; D018950:Lipopolysaccharide Receptors; D008077:Lipoproteins, LDL; C032629:acetyl-LDL; D000469:Alkaline Phosphatase; D001374:Azacitidine; D002118:Calcium