Role of bone marrow mesenchymal stem cell in the stabilization of elastace-induced ascending aortic aneurysm in a rat model

TITLE: Role of bone marrow mesenchymal stem cells in the stabilization of elastase- induced ascending aortic aneurysm in a rat model BACKGROUND: Aortic ascending aneurysm (AAA) is the 18th cause of mortality in the developed countries. The most recent pathophysiological hypothesis proposes the key role of stress-induced pathways both in endothelial cells (ECs) lining vasa vasorum and vascular aortic smooth muscle cells (VSMCs) activated by biochemical/mechanical inciting stimuli. Our purpose is to create an AAA model in rat that reproduces main structural features of AAA in human beings. At the same time we sought to investigate the role of Bone Marrow Mesenchymal Stem Cells (BM-MSC) in the stabilization of already formed AAA to limit aortic dilatation and to prevent deadly complications. PRELIMINARY RESULTS: Stress-induced pathways create a typical phenotypic switching both in EC and VSMC cells determining production and release of numerous mitotic and trophic factors, proteoglycans and metalloproteinases (MMP­)s, such as MMP-2 and 9. As result, different cellular and extracellular mechanisms are induced and determine sporadic AAA onset and progression as a multifactorial process with several steps. Consequent manifestations are the dissection followed or associated with expansion and rupture of aortic wall. In expanding experimental aortic aneurysms, correction of depletion in VSMCs triggers wall reconstruction and stabilizes the diameter of the disease aorta. A subset of BM-MSCs have been shown to differentiate, in vitro, into VSMC-like cells upon platelet derived growth factor B (PDGF-B) stimulation. In vivo, BM-MSCs have been shown to contribute to healing of mechanically injured arteries. In particular, Schneider et al. showed that mesenchymal stem cells stabilize already formed aortic abdominal aneurysm more efficiently than VSMCs in rat model. In relationship to AAA, BM- derived EPC have been studied as a novel biomarker to assess the severity of the pathology, but no studies have been performed to investigate the role of EPC in limiting AAA dilatation and in preventing catastrophic complications like rupture and dissection. FUTURE PERSPECTIVES: Assessing the role of EPC as the regenerative therapy of AAA in rat, after we want to perform the same experiment in a pig model and finally investigate the role of BM-MSCs in humans. It’s can change the management of patients of AAA and in the same time reduce the incidence of rupture and dissection in particular in case of small aneurysm. COOPERATION REQUEST: We need a cooperation between cardiac surgeons , genetics and pathologists. It’s necessary a laboratory were I can realize my animal models.