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Date of Award

6-2020

Document Type

Restricted Thesis: Campus only access

Degree Name

Master of Science in Biology

Department

Biology

First Reader/Committee Chair

Bournias-Vardiabasis, Nicole

Abstract

Myocardial infarctions affect approximately 735,000 people annually in the United States and have a substantial impact on the quality of life. Neonates have an enhanced capability of repairing cardiovascular damage, while adult human heart tissue does not regenerate. The mechanistic basis for this age-dependent difference in regenerative capacity remains unknown. Recent studies have shown that microRNAs (miRNAs) play a significant role in the regenerative ability of cardiac stem cells. The objective of this project is to distinguish alterations in miRNA expression in myocardial infarcted sheep hearts following injection of ovine neonatal ISL1+ cardiac progenitor cells (CPCs) for cardiac repair. We hypothesize that transcripts encoding miRNAs associated with enhanced stemness, cell division, and survival will be differentially regulated. To understand the role of miRNA expression associated with the regenerating myocardium, a sheep model of myocardial infarction was used to identify the miRNAs induced in the neonatal CPC-treated region of the myocardial repair. Nine microRNAs were differentially regulated in vivo, including miR-99, miR-100, miR-302a, miR-208a, miR-665, miR-1, miR-499a, miR-34a, and miR-133a. Each of these microRNAs function in promoting cardiovascular regeneration. Our study validated the role of select miRNAs and identified several new miRNA transcripts involved in neonatal CPC-mediated cardiovascular repair. This information can be used to design new approaches to further optimize cell-based treatments for the heart.

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