Date of Graduation

8-2025

Document Type

Dissertation

Degree Name

Doctor of Philosophy in Engineering (PhD)

Degree Level

Graduate

Department

Biomedical Engineering

Advisor/Mentor

Rao, Raj

Committee Member

Jeffrey Wolchok

Second Committee Member

Jorge Almodovar

Third Committee Member

Kartik Balachandran

Fourth Committee Member

Younghye Song

Keywords

Cardiovascular disease; Culture conditions; Differentiation; Regenerative medicine; Smooth muscle cells; Stem cells

Abstract

This dissertation examines the role of vascular smooth muscle cells (VSMCs) in vascular disease and the potential of stem cell-derived VSMCs (SC-SMCs) for regenerative medicine. VSMCs are crucial for maintaining function; however, their dysregulation contributes to the progression of diseases like atherosclerosis, vascular calcification, and aneurysms. Disease progression is influenced by various environmental factors, prompting VSMCs to switch phenotypes, leading to adverse vascular remodeling. This research focuses on adult bone marrow mesenchymal stem cells (BM-MSCs) and adipose-derived stem cells (ADSCs) as sources for generating reparative VSMCs. Through comparative analysis, it investigates the effects of SC-SMCs on VSMC biomarker expression and ECM composition, considering different differentiation conditions and serum presence. The findings highlight distinct functional capacities and biomarker profiles of VSMCs derived from BM-MSCs versus ADSCs. The dissertation further explores molecular mechanisms behind VSMC phenotypic changes and the reparative properties of SC-SMC CM in ECM repair and anti-inflammatory actions. It discusses optimizing SC differentiation to improve VSMC functionality and standardizing protocols for vascular tissue engineering (VTE). The role of mechanobiology, miRNA, and epigenetics in SMC phenotype regulation is also analyzed, providing a holistic approach to vascular repair. The dissertation outlines the challenges of translating these cellular and molecular insights into clinical strategies for vascular pathologies. It highlights the need for advanced materials and scaffolds to support vascular tissue regeneration and repair. Future research directions include longitudinal studies to monitor VSMC phenotypes, non-invasive imaging for in vivo tracking, and systems biology to enhance VTE therapies. In conclusion, the dissertation contributes to the understanding of VSMCs in vascular health and disease, advocating for the use of stem cell technologies in developing novel vascular therapies. A multi-disciplinary approach is called for to address the challenges in the field and improve the treatment options for vascular diseases.

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