Abstract 15949: The Inflammatory Niche and Aberrant Differentiation of Vascular Stem Cells in Ectopic Calcification of Atherosclerotic Plaque
Mounting evidence suggests that vascular calcification is as an active cell controlled event. We hypothesized that in presence of inflammatory cytokines seen in atherosclerotic environment, a pericyte-like stem cells population, termed vessel derived stem cells (VSCs), and circulating mesenchymal stem cells (MSCs), contribute to the calcification of atherosclerotic plaque via endochondral ossification. VSCs from aortae of ApoE-/- mice and background C57Bl/6 mice were isolated and characterized. To assess their ability to form bone, cells were seeded onto collagen glycosaminoglycan scaffolds and primed chondrogenically in vitro followed by subcutaneous implantation in ApoE-/- and C57BL/6 mice for 8 weeks. ApoE-/- MSC and VSC constructs formed bone when implanted in C57BL/6 mice (Fig.1 and Table 1). Also, ApoE-/- MSC and ApoE-/- VSC constructs generated more mature bone in ApoE-/- mice (Fig.1) than C57BL/6 MSC and VSC constructs (Table 1). To interrogate the mechanism, the effect of proinflammatory cytokines associated with the atherosclerotic niche on chondrogenic differentiation in vitro was assessed. At 21 days following IL-6 treatment, ApoE-/- VSCs showed increased levels of Sox9, fibromodulin, type II collagen, aggrecan and alkaline phosphatase. That both MSCs and VSCs from the ApoE-/- atherosclerotic mice generate a more mature hypertrophic chondrocyte than cells from the C57BL/6 mice is a novel finding and suggests that the atherosclerotic environment may modulate the stem cell phenotype. Improved bone formation from ApoE-/- cells as well as in the ApoE-/- animals using wild type cells illustrated that the cell and environment are important for bone formation.
Author Disclosures: A. Leszczynska: None. A. O’Doherty: None. E. Farrell: None. F. O’Brien: None. T. O’Brien: None. M. Murphy: None.
- © 2014 by American Heart Association, Inc.