Abstract 20944: Perivascular Progenitor Cells Contribute To Neointima Formation After Wire-induced Injury
Bone marrow-derived progenitor cells (BMPCs) as well as perivascular progenitor cells have been implicated to differentiate into vascular cells during neointima formation. The objective of this study was to assess the contribution of progenitor cells to the cellular neointimal mass. Wire-induced injury of the femoral artery was performed on chimeric C57BL/6 mice transplanted with bone marrow from transgenic mice expressing enhanced green fluorescence protein (EGFP). Vessels were harvested at 1, 2, 4, 6 and 16 weeks after dilation (n=8 animals per time point) and analyzed using confocal microscopy. Most of the accumulating EGFP+-cells were identified as inflammatory cells (CD45, CD68), and their number in the neointima declined from 110.81±18.98 at 2 weeks to only 5.31±2.21 at 16 weeks after dilation. Whereas very few EGFP+-cells co-expressed α-smooth muscle actin or CD31, expression of smooth muscle myosin heavy chain or von Willebrand Factor was not detected in BM-derived cells at any time point. Interestingly, a substantial expression of stem cell antigen (Sca)-1 was detected in proliferating EGFP negative cells in the adventitial layer, but only a small fraction of BM-derived cells accumulating at the arterial lesion site co-expressed Sca−1. At 4 weeks after dilation, the absolute number of adventitial Sca-1+-cells increased from 47.88±7.18 cells/slide in non-injured arteries to 158.5±16.656 cells/slide and the fraction of proliferating cells rose to 14.94% of all adventitial cells. Even though recent in vitro data have shown that perivascular progenitor cells lose Sca-1 from their cell surface when differentiating into smooth muscle-like cells, we also detected singular Sca-1+/EGFP--cells within the neointimal lesion, indicating that these cells indeed migrate toward the luminal site. In conclusion, we provide evidence that BMPCs within the neointima rarely co-express markers for vascular cells and do not contribute to the neointimal cellular mass beyond the inflammatory response. In contrast, the high proliferation rates of perivascular progenitor cells indicate a possibly substantial contribution of this cell fraction to the development of the neointimal lesion.
- © 2010 by American Heart Association, Inc.