title: Cell-Surface MMP-9 Protein Is a Novel Functional Marker to Identify and Separate Proangiogenic Cells from Early Endothelial Progenitor Cells Derived from CD133(+) Cells.
abstract: To develop cell therapies for ischemic diseases, endothelial progenitor cells (EPCs) have been expected to play a pivotal role in vascular regeneration. It is desirable to use a molecular marker that is related to the function of the cells. Here, a quantitative polymerase chain reaction array revealed that early EPCs derived from CD133(+) cells exhibited significant expression of MMP-9. Some populations of early EPCs expressed MMP-9 on the cell surface and others did not. We also attempted to separate the proangiogenic fraction from early EPCs derived from CD133(+) cells using a functional cell surface marker, and we then analyzed the MMP-9(+) and MMP-9(-) cell fractions. The MMP-9(+) cells not only revealed higher invasion ability but also produced a high amount of IL-8. Moreover, the stimulative effect of MMP-9(+) cells on angiogenesis in vitro and in vivo was prohibited by anti-IL-8 antibody. These data indicate that MMP-9 is one of the useful cell surface markers for the separation of angiogenic cells. Our treatment of early EPCs with hyaluronidase caused not only a downregulation of cell-surface MMP-9 but also a decrease in invasion ability, indicating that membrane-bound MMP-9, which is one of the useful markers for early EPCs, plays an important role in angiogenesis. Stem Cells 2016;34:1251-1262.
authors.affiliation: Department of Pharmacology, Nihon Pharmaceutical University, Inamachi, Saitama, Japan.|Division of Microbiology, National Institute of Health Sciences, Tokyo, Japan.
authors.forename: Toshie
authors.initials: T
authors.lastname: Kanayasu-Toyoda
authors.affiliation: Department of Pharmacology, Nihon Pharmaceutical University, Inamachi, Saitama, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Tanaka
authors.affiliation: Division of Microbiology, National Institute of Health Sciences, Tokyo, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Kikuchi
authors.affiliation: Division of Molecular Target and Gene Therapy Products, National Institute of Health Sciences, Tokyo, Japan.
authors.forename: Eriko
authors.initials: E
authors.lastname: Uchida
authors.affiliation: National Institute of Biomedical Innovation, Ibaraki-City, Osaka, Japan.
authors.forename: Akifumi
authors.initials: A
authors.lastname: Matsuyama
authors.affiliation: Department of Pharmacology, Nihon Pharmaceutical University, Inamachi, Saitama, Japan.|Division of Microbiology, National Institute of Health Sciences, Tokyo, Japan.
authors.forename: Teruhide
authors.initials: T
authors.lastname: Yamaguchi
mesh_terms: D000071916:AC133 Antigen / Q000378:metabolism*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002458:Cell Fractionation; D002462:Cell Membrane / Q000201:enzymology*; D002469:Cell Separation; D066026:Endothelial Progenitor Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D006614:Hindlimb / Q000098:blood supply / Q000473:pathology; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D006821:Hyaluronoglucosaminidase / Q000494:pharmacology; D016209:Interleukin-8 / Q000378:metabolism; D007511:Ischemia / Q000473:pathology; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D061965:Matrix Metalloproteinase Inhibitors / Q000494:pharmacology; D051379:Mice; D018919:Neovascularization, Physiologic / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: D000071916:AC133 Antigen; D015415:Biomarkers; D016209:Interleukin-8; D061965:Matrix Metalloproteinase Inhibitors; D012333:RNA, Messenger; D006821:Hyaluronoglucosaminidase; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9
keywords: Angiogenesis; CD133; Cell therapy; Endothelial progenitor cells; Matrix metalloproteinases