College - Author 1
College of Engineering
Department - Author 1
Biomedical Engineering Department
Degree Name - Author 1
BS in Biomedical Engineering
Date
9-2026
Primary Advisor
Trevor Cardinal, College of Engineering, Biomedical Engineering Department
Abstract/Summary
Peripheral Artery Occlusive Disease (PAOD) is a cardiovascular disease that affects more than 200 million people. It is characterized by atherosclerosis, a biologic process where peripheral arteries are restricted due to a buildup in cholesterol and fats. This eventually leads to ischemia, developing complications such as chronic inflammation and possible limb amputation. The current standard of care for patients includes surgical revascularization and exercise therapy. These treatment strategies have had limited success with alleviating symptoms and restoring perfusion, however, many patients still experience ischemia and do not fully restore blood flow. Further exploration in pursuit of treating these shortcomings led to investigations into the cellular mechanisms involved with blood flow including arteriogenesis. This is the biological event where a collateral arteriole enlarges to divert blood flow around a blockage, the chronic inflammatory environment and overall unhealthy tissue in patients with PAOD usually prevent arteriogenesis from being performed. This has led to investigating growth factors and cellular therapies to target arteriogenesis, Unfortunately, targeting arteriogenesis by paracrine factors, such as VEGF-A, largely failed in clinical trials, demanding more dynamic and novel therapeutic approaches such as cellular therapies. Early cellular therapies attempted introducing bone marrow derived mononuclear cells, hoping that they would stimulate blood vessel growth and rescue perfusion with progenitor cells. Similar approaches with mesenchymal stem cells also failed. These therapies failed to improve collateral vessel growth or perfusion, because they may not have sufficiently affected the core cellular mechanisms at play. New approaches are necessary to coordinate these cellular mechanisms. One promising cell therapy is myoblasts; the muscle progenitor cells associated with skeletal muscle growth and hypertrophy. It is well established that muscle growth benefits patients with PAOD, as a result, myoblasts are an interesting approach due to their association with exercise therapy and their known interactions with cells controlling arteriogenesis, specifically macrophages. Previous work in our lab has demonstrated that mouse myoblasts promote arteriogenesis in DIO mice and promote regenerative, anti-inflammatory phenotypes in mouse macrophages in vitro. By assessing how myoblasts may mediate macrophage polarization towards a pro-regenerative (M2) state, myoblasts can be evaluated to see how they combat the inflamed environment. Macrophage polarization can be determined using their marker expression, including CD80 for M1 and CD206 for M2. In addition to this, macrophage morphology between the two states can differ in both size and shape. Presumptive M1s exhibited larger diameters and more spindles, however, presumptive M2 morphology remained unchanged and indistinguishable from presumptive M0s. Cells were provided with various factors to induce M1-like or M2-like phenotypes. M1-like cells had higher CD80 expression and larger cell diameters. M2-like cells had unremarkable morphology, like naïve macrophages. Future studies will further evaluate marker expression and morphology to further validate our polarization protocol. Polarized macrophages will then be cocultured with myoblasts to observe how myoblasts modulate macrophage populations/activation in human cells.
URL: https://digitalcommons.calpoly.edu/bmedsp/233