Computer Aided Design and Initial Testing of a Novel Stem Cell Based Therapy for Abdominal Aortic Aneurysms

摘要

Exsanguination from abdominal aortic aneurysm (AAA) rupture is frequently fatal and is currently the 13th leading cause of death in the United States of America. AAAs can take years to progress to the point where surgical intervention is recommended (> 5.5 cm diameter). Surgical intervention does not benefit small AAAs, and management of these patients is limited to "watchful waiting" (i.e., serial imaging of the AAA progression until the threshold for surgical treatment is met).;The goal of this dissertation is to develop a novel stem cell therapy for small AAAs. Approximately 90% of patients with AAA do not meet the size criterion for intervention and could benefit from this alternative therapy.;In short, our proposed strategy is delivery of adipose-derived mesenchymal stem cells to the external surface of the AAA. In this way autologous cells can be isolated from a patient, culture-expanded if necessary, mixed in a hydrogel, and injected around that same patient's aorta in a minimally invasive procedure. The work of this dissertation represents four foundational steps towards design and initial evaluation of the proposed therapy: evaluation of the potential of SMCs to produce elastin in vitro, assessment of the effects of elastin production in silico, demonstration of efficacy in a small animal model, and fabrication of a new self-mixing injector device for human use.