Impact of CpG methylation in addressing adipose-derived stem cell differentiation towards the cardiac phenotype

Cardiovascular diseases are a major cause of mortality in industrialized countries. Patients who survive after an acute myocardial infarction (AMI) are prone to ventricular remodelling, resulting from loss of myocardial tissue, and to progressive chronic heart failure (CHF). Heart has just a minimal potential of repair and regeneration, thus the use of new strategies of treatment involving stem-cell transplantation and/or endogenous stem cell mobilization is expected as a promising alternative to standard therapy. Stem cells are undifferentiated cells with self-renewal and differentiation potential. Among stem cells, embryonic (ESCs) are considered as the best for cardiac regeneration (Nir et al., 2003); on the other hand several issues, including ethical questions, immunorejection and teratoma formation, limit their practical use. To overcome these restrictions, research interest is focusing on adult stem cells, indentified in different tissues and resulted able to differentiate towards the cardiac phenotype. Stem cells obtained from bone marrow, contain a subpopulation of hematopoietic stem cells (HSCs) (Goodell et al., 1997), a component of mesenchymal stem cells (MSCs) (Pittenger and Martin, 2004) and multipotent progenitor cells (MAPCs) (Jiang et al., 2002). MSCs derived from bone-marrow show some potential of differentiation into beating cardiomyocytes in vitro (Makino et al., 1999; Hakuno et al., 2002; Fukuda, 2001; Toma et al., 2002). Somatic stem cells also include endothelial progenitor cells (EPCs), obtained from peripheral circulation (Badorff et al., 2003), and cells arisen from umbilical cord (USSCs). USSCs showed capacity of differentiation towards the cardiac phenotype and to promote angiogenesis (Badorff et al., 2003; Kogler et al., 2004). Resident stem cells, located in cardiac niches, showed a differentiation potential towards cardiomyocites (Bollini et al., 2010]. In the last decade another group of somatic stem cells, derived from adipose tissue (ADSCs) was studied, most of all for their easy way of extraction, relative abundance and differentiative capacity towards different lineages. This chapter will focus on this last family of somatic stem cells. We will describe the features of ADSCs, how to isolate them from lipoaspirates, their cell surface markers and their differentiative potential. We will also report of ADSCs ability to differentiate into cardiomyocytes. Finally we will outline the epigenetic signature of ADSCs, to define if epigenetic modifications could influence their commitment towards a specific phenotype.