Abstract P031: Enhanced Cardiac Progenitor Cell Function and Differentiation in a Naturally Derived Extracellular Matrix
Cardiovascular disease, including myocardial infarction, is a leading cause of death worldwide. Though several pharmacological treatments for severe dysfunction exist, much recent work has focused on the transplantation of adult-derived stem and progenitor cells. Early acute functional improvements have been noted, however long-term clinical efficacy is hampered by poor cell survival and engraftment. While the current treatment is infusion into the coronary artery, biomaterials may play an important role in modulating implanted cell function. This work aims to establish the role that a naturally derived extracellular matrix plays in the differentiation of cardiac progenitor cells (CPCs) and their potentially protective enzymatic systems. To test this hypothesis, we cultured rat CPCs in a naturally derived porcine ECM (pECM) and compared it to Collagen I. Quantitative real-time PCR was used to assess expression of cardiac, endothelial and smooth muscle markers. Additionally, angiotensin receptor (AT1R and AT2R) and antioxidant gene expressions were evaluated to determine the protective qualities of pECM. Preliminary data at 2 days following LIF removal demonstrate an increase in the expression of cardiac lineage markers (Nkx-2.5, Gata-4, α-MHC, and troponin I) in pECM compared to collagen. Smooth muscle markers, smooth muscle α-actin and sm22α as well as the endothelial marker Flk1 were also increased in pECM samples. Increased expression was also seen for antioxidant genes GPX1, SOD1, SOD2 and catalase in pECM cultured cells. Culturing in pECM for 7 days demonstrated an increase in Flt-1 and α-myosin heavy chain, indicating a potential increase in cardiogenesis. Moreover a 60% reduction in AT1R gene expression was observed with no significant change in AT2R expression. Our data demonstrate that culturing CPCs in naturally derived matrices may provide protection and enhance differentiation compared to collagen (present in high amounts in scarred myocardium). Future work will further elucidate this protective effect of AT1R downregulation and antioxidant increases in functional studies. In conclusion, pECM may be a potential cell delivery scaffold in post-MI treatment given its protective nature and improved differentiation influence.
- © 2011 by American Heart Association, Inc.