College - Author 1

College of Engineering

Department - Author 1

Biomedical Engineering Department

Degree Name - Author 1

BS in Biomedical Engineering

Date

6-2021

Primary Advisor

Trevor R. Cardinal, College of Engineering, Biomedical Engineering Department

Abstract/Summary

Gangrene, pain, loss of limb function, amputation, and death are only few of the grievous consequences associated with peripheral arterial disease (PAD), a vascular disease caused by an obstruction that narrows the blood vessels. Since some patients have collateral vessels that can re-route blood to its downstream destination, much focus has been spotlighted upon discovering the mechanism of this process, termed arteriogenesis, as well as cell therapies to increase arterial diameter of collateral vessels. Since some patients do not have native pre-existing collateral vessels, another method to re-route blood is through arterialized collateral capillaries (ACC), which is the conversion of capillaries to arterioles. Because the delivery of pro-arteriogenic cell therapies did not have much clinical success, another candidate is needed to treat PAD: myogenic precursor cells. Preliminary, unpublished results demonstrated myogenic cell transplantation enhanced collateral capillary arterialization. Specifically, the diameter of arterialized collateral capillaries due to myoblast treatment is larger when compared to the vehicle alone and untreated groups. The current working hypothesis suggests that myoblasts and macrophages have a reciprocal paracrine interaction in which macrophages secrete cytokines and chemokines for the myoblasts to mature, and that certain genes in myoblasts are expressed as cytokines and chemokines to encourage macrophage recruitment and M2 macrophage polarization, which promotes arteriogenesis. To test this hypothesis, the expression of target genes in myoblasts would be measured using RNA sequencing and Western blotting for measuring proteins, macrophage phenotype and quantity would be determined in vivo along with vessel diameter with immunofluorescence staining. This senior thesis describes the studies that would need to be completed to test the hypothesis stated above, including example

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