title: Differential MMP-9 activity in CD34⁺progenitor cell-derived foam cells from diabetic and normoglycemic patients.
abstract: BACKGROUND
  Upon coincubation with platelet aggregates, CD34(+) progenitor cells have the potential to differentiate into foam cells. There is evidence that progenitor cells from diabetic and nondiabetic patients have different properties, which may affect the patients' prognosis. In this study we investigated an in vitro model of foam cell formation based on patient-derived CD34(+) progenitor cells. We analyzed the growth characteristics as well as the M-CSF-release and matrix metalloproteinase (MMP) synthesis from CD34(+) progenitor cell-derived foam cells originating from diabetic and nondiabetic patients.
  
  
  RESULTS
  Bone marrow samples were obtained from 38 patients who were elected for thoracic surgery. CD34(+) progenitor cells from diabetic and nondiabetic patients were isolated and incubated with platelets from healthy volunteers. Foam cell formation was confirmed by immunostaining (CD68) and quantified by light microscopy. Whereas the absolute number of foam cells was not affected, the negative slope in the growth curve was seen significantly later in the diabetic group. In supernatants derived from"diabetic" CD34(+) progenitor cells, MMP-9 was significantly enhanced, whereas MMP-2 activity or M-CSF-release was not affected significantly.
  
  
  CONCLUSIONS
  In a coculture model of CD34(+) progenitor cells with platelets, we show for the first time that"diabetic" CD34(+) progenitor cells exhibit functional differences in their differentiation to foam cells concerning growth characteristics and release of MMP-9.
authors.affiliation: Medizinische Klinik II, Hämatologie, Onkologie, Immunologie, Rheumatologie und Pulmologie, Eberhard Karls University of Tübingen, Otfried-Müller-Str. 10, 72076, Tübingen, Germany, joerg.schmohl@med.uni-tuebingen.de.
authors.forename: J U
authors.initials: JU
authors.lastname: Schmohl
authors.forename: K
authors.initials: K
authors.lastname: Daub
authors.forename: S N I
authors.initials: SN
authors.lastname: von Ungern-Sternberg
authors.forename: S
authors.initials: S
authors.lastname: Lindemann
authors.forename: T
authors.initials: T
authors.lastname: Schönberger
authors.forename: T
authors.initials: T
authors.lastname: Geisler
authors.forename: M
authors.initials: M
authors.lastname: Gawaz
authors.forename: P
authors.initials: P
authors.lastname: Seizer
mesh_terms: D000368:Aged; D018952:Antigens, CD34 / Q000378:metabolism; D001792:Blood Platelets / Q000201:enzymology / Q000473:pathology; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D018920:Coculture Techniques; D003920:Diabetes Mellitus / Q000201:enzymology* / Q000473:pathology*; D004789:Enzyme Activation; D005260:Female; D005487:Foam Cells / Q000201:enzymology* / Q000473:pathology*; D006801:Humans; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D059630:Mesenchymal Stem Cells / Q000201:enzymology / Q000473:pathology*
chemical_list: D018952:Antigens, CD34; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9