Mount Sinai School of Medicine
Therapeutic assessment of combined endovascular aneurysm repair (EVAR) stent grafting and stem cell therapy in porcine models of abdominal aortic aneurysms.
Abdominal aortic aneurysms (AAAs) are responsible for up to 6% of all deaths caused by cardiovascular disease. For patients with AAAs exceeding 5 cm, endovascular aneurysm repair (EVAR) has reduced the morbidity and mortality associated with standard open operative repair. However, the pathophysiologic processes underlying AAA formation fail to self-correct following aneurysm sac exclusion with EVAR. As a result, novel therapies are required to allow for arterial wall regeneration following EVAR intervention. Bone marrow-derived mesenchymal stem cells (MSCs) have been shown to induce regenerative effects when transplanted directly into a variety of tissue, including myocardium. It is therefore hypothesized that combined EVAR and MSC therapy may allow for the effective regeneration of the arterial wall in porcine models of AAAs. In order to evaluate MSC placement and migration within the aneurysm sac, the MSCs will be labeled with iron oxide particles to allow for in vivo detection by Magnetic Resonance Imaging (MRI). MRI may also be used to evaluate morphologic and functional (variation in blood flow) changes in the AAA in response to the EVAR/MSC treatment. To evaluate the efficacy of combined EVAR/MSC treatment we have formulated the following aims: Aim 1 will address issues related to iron oxide cell labeling and the effect of labeling on the phenotypic properties of porcine MSCs. Aim 2 will focus on the optimization and validation of the MR imaging methodology. Aim 3 will determine the ability to detect and monitor transplanted MSCs in vivo. Additionally, the regenerative properties of the transplanted MSCs will be evaluated by comparing morphologic and functional changes observed in EVAR/MSC treated pigs to control EVAR stented pigs (no cell treatment). Due to the complexity of the proposed project, the current study requires a combined effort from the Departments of Vascular Surgery, Radiology, and Gene and Cell Medicine.