Abstract 19453: Bone Marrow Mononuclear Cells Contribute to the Vascular Hematopoietic Niche
Background: There is an integral relationship between the vasculature and hematopoietic cells in health and disease. We have previously identified a variety of hematopoietic stem and progenitor cells in the aorta of normal and atherosclerotic mice. We hypothesize that bone marrow cells may contribute to the origin of these populations.
Methods: Nonirradiated and irradiated (1100cGy) C57BL/6 mice received bone marrow cells from GFP donors via tail vein injections. Mice (n=6/group) were sacrificed up to 6 weeks following delivery. The presence of GFP positive cells was assessed by flow cytometry and immunohistochemistry. Short term culture in methylcellulose was used to define their hematopoietic clonogenic potential.
Results: GFP+ cells in recipient aortas were extremely sparse in aortic specimens from non-irradiated mice (0.03±0.01%) 1 week post infusion. In irradiated recipients after 1 day, recovery of hematopoietic colony forming units (CFU) from single-cell aortic disaggregates was low as was aortic wall chimerism (0.6±0.2%). 4–6 weeks following delivery, flow cytometric analysis of single cell aortic disaggregates demonstrated 46±6% cells expressing GFP. Amongst GFP+ aortic cells, stem cell markers were expressed, including sca-1 (13±5%), c-kit (0.7±0.5%) and CD34 (0.7±0.3%), while coexpression of sca-1/c-kit was 0.5±0.4%. Immunohistochemistry showed the presence of donor GFP+ cells confined to the adventitia along the entire aorta. Short term culture of the single cell aortic disaggregates from irradiated mice generated GFP+ CFU erythrocyte, megakaryocyte, macrophage, with a preponderance of CFU macrophage (p<0.05 vs. other CFUs).
Conclusions: We demonstrated, for the first time, a radiation-sensitive vascular hematopoietic niche. Bone marrow cells homing to this niche following radiation injury are capable of forming a diverse array of hematopoietic colonies favoring macrophage potential. These findings have implications for the understanding of radiation-induced vascular injury.
- © 2010 by American Heart Association, Inc.