Cardiac Progenitor Cell Differentiation by Isoxazole and Decellularized Cardiac Extracellular Matrix
Yurkanin, Melissa A.
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In recent years, cardiovascular disease has become a significant detriment to health in the Western world. Many people consume unhealthy diets that accelerate the progression of arterial plaque accumulation, which can potentially lead to thrombosis. This lack of blood flow to the heart consequently results in a myocardial infarction. The damage from such an episode includes scar tissue formation on the affected areas and death of cardiomyocytes. Until recently, it was hypothesized that reversal of this damage was impossible. The discovery of cardiac progenitor cells, however, brings new hope that populations of cardiomyocytes can be reseeded on necrotic tissue. Using in vitro experimentation, it has been shown that differentiation of cardiac progenitor cells into cardiomyocytes through cell culture can be further accelerated when seeded on decellularized cardiac extracellular matrix (dECM) and treated with small molecules. Therefore, we chose to magnetically sort for cardiac progenitor cells expressing the progenitor cell marker Flk-1 (Flk-1+ cells) and seed them on dECM. Cells that did not express the Flk-1 gene (Flk-1- cells) were seeded on either laminin (control) or dECM. We then treated individual samples in each group with either the control vehicle or varying concentrations of the small molecule isoxazole, a molecule known to aid in the maturation of progenitor cells. Gene expression was determined for progenitor, mesodermal, myocardial, and endothelial genes using qRT-PCR. Up-regulation of myocardial genes was greatest for Flk-1+ samples seeded on dECM administered 20 μM of isoxazole. Flk-1+ cells seeded on dECM that have successfully matured into cardiomyocytes could be surgically implanted on top cardiac scar tissue to repopulate the tissue with cardiomyocytes and repair necrotic fibers. After repair, the heart would then be able to function at its original capacity, restoring health to those who have suffered a myocardial infarction.
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