Differentiation, Characterization and Applications of Human Embryonic Stem Cell –Derived Cardiomyocytes

Abstract

The term “embryonic stem (ES) cell” was introduced in 1981 to distinguish embryo-derived pluripotent cells from teratocarcinoma-derived pluripotent embryonal carcinoma (EC) cells (Martin 1981). First ES cells were derived from mouse intracellular mass (ICM) in the same year (Evans and Kaufman 1981) and in 1994 Bongso and co-workers reported the successful isolation of human ICM cells and their continued culture for at least two passages in vitro (Bongso, Fong et al. 1994). The first permanent human embryonic stem cell (hESC) lines were derived more than a decade ago by Thomson and co-workers (Thomson, ItskovitzEldor et al. 1998) and these lines are still widely used. hESCs are capable of proliferating extensively at undifferentiated state in vitro and have the ablity to differentiate towards all three germ layers and furthermore can, in principle, give rise to all cell types of the body. Adult human cardiomyocytes have limited capability to regenerate and the heart tissue cannot undergo extensive repair needed for example after myocardial infarction. Therefore, the rapid development of stem cell technology has raised hopes for new treatments for tissue damage of cardiac and other tissues with limited regenerative capacity. Human embryonic stem cells (hESC) have the ability to differentiate into functional cardiomyocytes by multiple differentiation methods. Traditionally hESCderived cardiomyocytes (hESC-CM) are differentiated spontaneously in embryoid bodies (EB) or in co-culture with mouse endodermal cell like (END-2) cells (Kehat, KenyaginKarsenti et al. 2001; Mummery, Ward-van Oostwaard et al. 2003). In addition, more defined differentiation methods using growth factors have been developed (Laflamme, Chen et al. 2007; Yang, Soonpaa et al. 2008). However, the cardiac differentiation is still quite uncontrolled and inefficient and even though new more defined differentiation methods have been published, spontaneous differentiation in EBs and differentiation in co-culture with END-2 cells are still widely used as they are rather inexpensive and functioning for most of the hESC lines. At the end of the year 2009, the total number of hESC lines worldwide has been estimated to be 1071 (Loser, Schirm et al. 2010). Even though the number of hESC lines has increased steadily, two lines, H1 and H9 (WiCell Research Institute), are the most used ones in stem cell research (Guhr, Kurtz et al. 2006; Scott, McCormick et al. 2009; Loser, Schirm et al. 2010).