Electronic Thesis and Dissertation Repository

Degree

Master of Science

Program

Pathology

Supervisor

Zia A. Khan

Abstract

ii Abstract Abstract Defects in the proliferation, differentiation, and activity of bone marrow (BM)-derived vasculogenic/vascular stem cells (VSCs) have been observed in diabetes and contribute to the development of vascular complications. Diabetes leads to enhanced bone marrow adipogenesis, altering the composition of the BM stem cell (SC) niche and potentially disrupting the normal functioning of resident VSCs. Here, I establish that adipocytes have a negative influence on SC survival in culture. I also show that adipocytes and osteoblasts are responsible for the creation of distinct extracellular microenvironments, with unique expression patterns of several pro- and anti-angiogenic factors with known effects on VSCs, such as fibronectin, Notch ligands, stromal cell-derived factor-1, and angiopoietin-1 and -2. I conclude that alterations in marrow composition may mediate the connection between hyperglycemia, VSC dysfunction, and impaired vascular repair in diabetes.