A multimodal lens into vascular recovery in a preclinical model of peripheral arterial disease

angiogenesis, Stem-Cell, peripheral vascular disease, Imaging, Diabetes

Hedhli, Jamila

关键词: angiogenesis, Stem-Cell, peripheral vascular disease, Imaging, Diabetes;   

Others  :  https://www.ideals.illinois.edu/bitstream/handle/2142/102382/HEDHLI-DISSERTATION-2018.pdf?sequence=1&isAllowed=y

美国|英语

来源: The Illinois Digital Environment for Access to Learning and Scholarship

【 摘 要 】

In the week of February 2nd (21 days into gestation) my parents Ali, and Aicha heard my first heart beat. This shouldn't be a surprise as the heart is the first organ to form and function during the developmental stages of the fetus. In the embryo, newly formed blood vessels provide the growing organs with the vital oxygen and nutrients required for them to flourish.During adulthood, angiogenesis---the process by which new blood vessels form---remains largely quiescent until the delicate balance between pro- and anti-angiogenic factors is disrupted, either through injury or disease. Cardiovascular complications are among the leading causes of morbidity and mortality in diabetic patients, and account for over 80\% of diabetes-associated deaths.One of the most serious is peripheral arterial disease (PAD), which is defined as a narowing of the peripheral vasculature. In this thesis, I will employ a range of imaging modalities to study PAD, investigating methods that may one day enable earlier detection of the disease, and exploring the therapeutic potential of stem cells to treat vascular complications associated with diabetes. This document is divided into four main chapters. The first chapter describes the biological characterization of two different imaging probes targeted, respectively, at hypoxia and \avbt activity, as well as a new power Doppler ultrasound imaging technique capable of detecting small spatiotemporal changes in blood perfusion within muscle. The second chapters applies the \cuProbe peptide targeted at \avbt, to establish an optimal preclinical model of PAD. The third chapter builds on the first and second, by developing a multimodal approach for vascular imaging that enables simultaneous evaluation of molecular and physiological changes during angiogenesis. Finally, the fourth chapter turns its attention toward the mitigation of diabetes-associated PAD.In it, we show that a targeted stem cell-based therapy can exert far reaching effects on the ischemic tissue microenvironment, and may provide clinical improvement for PAD patients in the future.