5 azacytidine and ascorbic acid promote differentiation of cardiac stem cells to cardiomyocytes by down regulation of WNT signaling pathway

Abstract

Cardiovascular Diseases (CVDs) with loss of functional cardiomyocytes and irreversible damage to heart, remain the major cause of worldwide mortality and morbidity. Recent advances in stem cell therapy field gives hope to restore normal heart function by rejuvenating damaged myocardium with new functional cardiomyocytes. Cardiosphere Derived Cells (CDCs) are a type of Cardiac Stem Cells (CSCs) that express stemness and early cardiac markers, including but not limited to c-kit, Sca-1, Isl-1, MDR 1, Nkx 2.5 and GATA 4. CDCs are advantageous in myocardial regeneration therapy because of their clonogenic, anti-inflammatory and immunomodulatory properties along with the paracrine activity by secretion of growth factors. Development of an efficient and reliable protocol to direct CDCs from multipotent stage to cardiomyogenic state under in vitro conditions will newlineprovide an indispensable model to understand molecular mechanisms involved in differentiation. 5-Azacytidine (Aza), a known DNA methylation inhibitor and Ascorbic Acid (AA), a common co-factor in numerous biological reactions could influence self-renewal and differentiation of stem cells. Wnt/and#946;-catenin signaling pathway is highly conserved in the organisms and regulates cellular functions like proliferation, differentiation and maintenance both during normal development and diseased conditions. The present study was designed to evaluate the role of Aza alone or Aza+AA in mediating CDCs to cardiomyogenic lineage and to understand the involvement of Wnt/and#946;-catenin pathway in the same. newline newline