Differential MMP-9 activity in CD34+progenitor cell-derived foam cells from diabetic and normoglycemic patients

Abstract

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. 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. 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.