Date of Award
Master of Science in Biology
First Reader/Committee Chair
Heart failure affects many people around the world and can lead to disease progression and death. Consequently, new stem and exosome-based therapies are needed to address this major health issue and to provide therapeutic options that will improve outcomes for the increasing number of patients with heart disease. Stem cell-derived exosomes have captivated researchers’ attention over the past couple of years based on their functional role in cellular signaling which highlights the vital component of the secretome of stem and progenitor cells. Since neonates have significantly enhanced regenerative ability, we hypothesized that exosomes isolated from Islet-1+ expressing neonatal human cardiovascular progenitors (CPCs) will induce transcriptomic changes associated with improved regenerative capability when co-cultured with CPCs derived from adult humans. In order to test this hypothesis, we isolated exosomes from human neonatal Islet-1+ cardiovascular progenitor cell clones, analyzed the exosome content using RNAseq and treated adult CPCs with exosomes derived from neonatal CPCs to assess the functional effect. Analysis of neonatal CPC-derived exosome content by RNAseq revealed that neonatal exosomes contain miRNAs that inhibit YAP1 repressors and expressed transcripts predicted to activate YAP1, the cell cycle, and GPCR signaling. In vitro, adult CPCs treated with exosomes derived from neonatal CPCs demonstrated activation of AKT signaling, which promotes survival and proliferation and several transcripts involved in proliferation and cell cycle progression, including YAP1. YAP1 is lost after the neonatal period under normal development but can stimulate cardiac regeneration. Our results demonstrate that transcripts associated with enhanced regenerative effects can be induced in adult CPCs following treatment with neonatal CPC-derived exosomes. Our data suggests that neonatal Islet-1+ CPC exosome content can provide a stimulus that may improve functional outcomes when adult CPCs are used for cell-based cardiovascular repair.
Ceja, Lourdes, "NEONATAL ISLET-1+ CARDIOVASCULAR PROGENITOR CELL-DERIVED EXOSOMES AND THEIR FUNCTIONAL ABILITY TO REGULATE PROLIFERATION" (2022). Electronic Theses, Projects, and Dissertations. 1559.