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. / Biomedical Sciences
| Identifer | oai:union.ndltd.org:TEMPLE/oai:scholarshare.temple.edu:20.500.12613/4775 |
| Date | January 2020 |
| Creators | Hoachlandr-Hobby, Alexander, 0000-0001-5751-6372 |
| Contributors | Houser, Steven R., Sabri, Abdelkarim, Gallucci, Stefania, Kishore, Raj, Lindsey, Merry |
| Publisher | Temple University. Libraries |
| Source Sets | Temple University |
| Language | English |
| Detected Language | English |
| Type | Thesis/Dissertation, Text |
| Format | 96 pages |
| 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., http://rightsstatements.org/vocab/InC/1.0/ |
| Relation | http://dx.doi.org/10.34944/dspace/4757, Theses and Dissertations |
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