Embryonic stem cells: a model to study structural and functional properties in cardiomyogenesis.

Abstract

Time for primary review 20 days. In order to study cardiac myocyte development different approaches were established during the last decades. The main purpose of these studies was the differentiation of cardiac precursor cells into specialized, differentiated cell types, as well as the development of functional properties such as Ca2+ handling, rhythm generation and excitation-contraction coupling of cardiomyocytes during development. Although considerable data exist about skeletal myogenesis [1–3], limited knowledge is available with regard to the origin of the commitment and differentiation of cardiac cells. A comprehensive, morphological study on the cytodifferentiation from mesenchymal cells into cardiac myocytes is described in the embryonic murine heart [4]: According to the authors, different stages of myofibrillogenesis are present during embryological myocardial development. Cells with no or only little myofibrillar arrangement develop to myocardial cells with orientated myofibrils [5, 6]. A number of morphological studies have investigated heart development on embryonic, neonatal and adult isolated cardiomyocytes also from different species [7–16]. Although the ultrastructure during cardiac development has been thoroughly investigated [17], still relatively little is known on the development of excitability of the mammalian heart, most importantly: (1): The relation between expression of cardio-specific genes (see review [23]), the formation of cardiac phenotypes and the functional expression of different types of ion channels; (2): The regulation and genetic control of expression of ion channels (e.g. by growth factors, hormones, extracellular matrix); (3): The development of the regulation of ion channels and morphological correlates. The progress in this field is hampered by the inability to study cardiomyocytes from early, embryonal hearts because of their very small size and because of the lack of cardiac cell lines that mimic various stages of cardiac development. The development of ion currents has been studied in cardiomyocytes prepared from mammalian embryos … * Corresponding author. Tel.: (+49-221) 4786960; Fax: (+49-221) 4786965.