Generation of cardiomyocytes from embryonic stem cells experimental studies.

BACKGROUND

Cardiomyopathy is characterized by the loss of functional cardiomyocytes resulting in heart failure. More recently, there is increasing evidence from animal studies that transplantation of cardiomyocytes may represent a valuable approach for the treatment of severe heart failure.

DEVELOPMENT OF CARDIAC CELLS

Treatment of cardiovascular diseases using cardiomyocytes derived from embryonic stem cells prerequisites establishment of pure lineages of early embryonic cardiomyocytes from human embryonic stem cells. The development of cardiac cells from embryonic stem cells is regulated by several growth factors such as TGF-beta, IGF FGF and erythropoietin. After binding to their receptor, growth factors induce expression of a number of cardiac specific transcription factors such as the zinc finger GATA proteins and Nkx-2.5, a coactivator of the GATA-4 protein. The GATA-4 transcription factor and Nkx-2.5 are essential for heart development. In parallel to adult cardiomyocytes, embryonic stem cell-derived cardiomyocytes developmentally express cardiac specific proteins and ion channels.

GENERATION FROM EMBRYONIC STEM CELLS

Recently, it has been shown that pure cardiomyocytes can be generated from genetically manipulated embryonic stem cells. In order to achieve the selective cardiac differentiation of embryonic stem cells different culture conditions are currently tested to examine in the future the influence of different growth factors. However, although significant progress has been made in generating pure cardiomyocytes, further efforts are required to avoid possible immunological rejection of the engrafted cardiomyocytes. Thus, a main challenge in the future will be the establishment of pure lineages of cardiomyocytes derived from human embryonic stem cells.