Abstract 300: Mesenchymal Stem Cells Attenuate High-Mobility Group Box 1 to Inhibit Aortic Aneurysms

Objective: Mesenchymal stem cells (MSCs) have been shown to attenuate aortic aneurysms (AAs) in animal models, but their precise mechanism of action remains undefined. In this study, we hypothesize that MSCs modulate NADPH oxidase activity in macrophages to mitigate high mobility group box 1 (HMGB1; a proinflammatory nuclear protein) secretion causing attenuation of vascular inflammation and AA formation. Methods: Abdominal aortic tissue from male patients was obtained during open surgical repair and control aortic tissue was obtained from transplant donor patients. Human aortic tissue explants (or primary murine macrophages; 5x105 cells/well) were treated in vitro with elastase for 5 minutes, with or without co-culture with MSCs (1x105 cells per well) and supernatants were analyzed after 24hrs. In the murine in vivo model, AAs were induced in 8- to 12-week old C57BL/6 (WT) mice using an elastase-perfusion or heat inactivated elastase, with or without MSC treatment (given i.v. on day 1). Aortic tissue (ha...