Date of Graduation

5-2019

Document Type

Thesis

Degree Name

Bachelor of Science in Biomedical Engineering

Degree Level

Undergraduate

Department

Biomedical Engineering

Advisor/Mentor

Rao, Raj

Abstract

Abdominal aortic aneurysms (AAAs) are expansions in the aortic wall with an increased tendency to rupture. These expansions are triggered by the breakdown of key aortic extracellular matrix (ECM) proteins—elastin and collagen. The degradation of aortic ECM proteins is the consequence of overexpressed matrix metalloproteases (MMPs)–MMP-2 and MMP-9. Adult vascular smooth muscle cells (SMCs) lack the ability to repair the elastic matrix assembly; thus, it is imperative to find a solution to both restore the imbalance of essential ECM proteins in the aorta and mitigate the effects of MMPs. Previous studies have revealed that bone marrow derived mesenchymal stem cells (BM-MSCs) differentiated into smooth muscle-like cells (SMLCs) have the ability to induce elastic matrix assembly and reduce MMP-9 activity in aneurysmal rat aortic SMCs. The purpose of this study was to determine an optimal means to differentiate human BM-MSCs (hBM-MSCs) into SMLCs in order study these effects efficiently. Based on previous research, hBM-MSCs were plated onto fibronectin coated flasks and treated for four days with the following: differentiation medium (DM), DM with all-trans retinoic acid (atRA), DM with platelet-derived growth factor-BB (PDGF), and DM supplemented with both PDGF and transforming growth factor-β1 (TGF-β1). Western blot analysis revealed that untreated hBM-MSCs exhibit early and mid-stage SMC markers, SM22-α and caldesmon, but miniscule amounts of late-stage SMC marker, smooth muscle myosin heavy chain-11 (MYH11). Analysis also determined that treatment supplemented with both PDGF and TGF-β1 resulted in the highest expression of MYH11 and the least expression in stem cell marker, CD44.

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