OWNER OF A BROKEN HEART: STEM CELL THERAPY, INFLAMMATION, AND WOUND HEALING IN THE INFARCTED HEART
dc.contributor.advisor | Houser, Steven R. | |
dc.creator | Hoachlandr-Hobby, Alexander | |
dc.date.accessioned | 2021-01-18T20:22:18Z | |
dc.date.available | 2021-01-18T20:22:18Z | |
dc.date.issued | 2020 | |
dc.identifier.uri | http://hdl.handle.net/20.500.12613/4775 | |
dc.description.abstract | Acute damage to the heart, as in the case of myocardial infarction (MI), triggers a robust inflammatory response to the sterile injury and requires a complex and highly organized wound healing processes for survival. Cortical bone stem cell (CBSC) therapy has been shown to attenuate the decline in cardiac function associated with MI in both mouse and swine models. However, the cellular changes brought about by CBSC treatment and their relationship to inflammation and the wound healing process are unknown. We observed that CBSCs secrete paracrine factors known to have immunomodulatory properties, most notably Macrophage Colony Stimulating Factor (M-CSF) and Transforming Growth Factor-b, but not IL-4. Macrophages treated with CBSC medium containing these factors polarized to a hybrid M2a/M2c phenotype characterized by increased CD206 expression but not CD206 and CD163 co-expression, increased efferocytic ability, increased IL-10, TGF-b and IL-1RA secretion, and increased mitochondrial respiration in the absence of IL-4. Media from these macrophages increased proliferation and decreased a-Smooth Muscle Actin expression in fibroblasts in vitro. In addition, CBSC therapy increased macrophages, CD4+ T-cells, and fibroblasts while decreasing myocyte, macrophage, and total apoptosis in an in vivo swine model of MI. From these data, we conclude that CBSCs are modulating the immune response to MI in favor of an anti-inflammatory reparative response, ultimately reducing cell death and altering fibroblast populations resulting in smaller scar and preserved cardiac geometry and function. | |
dc.format.extent | 96 pages | |
dc.language.iso | eng | |
dc.publisher | Temple University. Libraries | |
dc.relation.ispartof | Theses and Dissertations | |
dc.rights | IN COPYRIGHT- This Rights Statement can be used for an Item that is in copyright. Using this statement implies that the organization making this Item available has determined that the Item is in copyright and either is the rights-holder, has obtained permission from the rights-holder(s) to make their Work(s) available, or makes the Item available under an exception or limitation to copyright (including Fair Use) that entitles it to make the Item available. | |
dc.rights.uri | http://rightsstatements.org/vocab/InC/1.0/ | |
dc.subject | Cellular biology | |
dc.subject | Medicine | |
dc.subject | Cardiology | |
dc.subject | Cardiovascular | |
dc.subject | Inflammation | |
dc.subject | Macrophage | |
dc.subject | Myocardial infarction | |
dc.subject | Stem cell therapy | |
dc.title | OWNER OF A BROKEN HEART: STEM CELL THERAPY, INFLAMMATION, AND WOUND HEALING IN THE INFARCTED HEART | |
dc.type | Text | |
dc.type.genre | Thesis/Dissertation | |
dc.contributor.committeemember | Sabri, Abdelkarim | |
dc.contributor.committeemember | Gallucci, Stefania | |
dc.contributor.committeemember | Kishore, Raj | |
dc.contributor.committeemember | Lindsey, Merry | |
dc.description.department | Biomedical Sciences | |
dc.relation.doi | http://dx.doi.org/10.34944/dspace/4757 | |
dc.ada.note | For Americans with Disabilities Act (ADA) accommodation, including help with reading this content, please contact scholarshare@temple.edu | |
dc.description.degree | Ph.D. | |
dc.identifier.proqst | 14268 | |
dc.creator.orcid | 0000-0001-5751-6372 | |
dc.date.updated | 2021-01-14T17:05:15Z | |
refterms.dateFOA | 2021-01-18T20:22:19Z | |
dc.identifier.filename | HoachlandrHobby_temple_0225E_14268.pdf |