Sachinidis Agapios, Kolossov Eugen, Fleischmann Bernd K, Hescheler Jürgen
Department of Neurophysiology, University of Cologne, Germany.
Herz. 2002 Nov;27(7):589-97. doi: 10.1007/s00059-002-2423-2.
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.
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.
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.
心肌病的特征是功能性心肌细胞丧失，导致心力衰竭。最近，动物研究越来越多地表明，心肌细胞移植可能是治疗严重心力衰竭的一种有价值的方法。
使用源自胚胎干细胞的心肌细胞治疗心血管疾病的前提是从人类胚胎干细胞建立早期胚胎心肌细胞的纯系。胚胎干细胞向心脏细胞的发育受多种生长因子调控，如转化生长因子-β、胰岛素样生长因子、成纤维细胞生长因子和促红细胞生成素。生长因子与其受体结合后，会诱导多种心脏特异性转录因子的表达，如锌指GATA蛋白和Nkx-2.5，后者是GATA-4蛋白的一种共激活因子。GATA-4转录因子和Nkx-2.5对心脏发育至关重要。与成年心肌细胞一样，胚胎干细胞衍生的心肌细胞在发育过程中表达心脏特异性蛋白和离子通道。
最近的研究表明，通过基因操作的胚胎干细胞可以生成纯心肌细胞。为了实现胚胎干细胞的选择性心脏分化，目前正在测试不同的培养条件，以便将来研究不同生长因子的影响。然而，尽管在生成纯心肌细胞方面取得了显著进展，但仍需要进一步努力以避免移植的心肌细胞可能出现的免疫排斥反应。因此，未来的一个主要挑战将是建立源自人类胚胎干细胞的心肌细胞纯系。
