Mummery Christine L, Zhang Jianhua, Ng Elizabeth S, Elliott David A, Elefanty Andrew G, Kamp Timothy J
Department of Anatomy and Embryology, Leiden University Medical Centre, Leiden, The Netherlands.
Circ Res. 2012 Jul 20;111(3):344-58. doi: 10.1161/CIRCRESAHA.110.227512.
Since human embryonic stem cells were first differentiated to beating cardiomyocytes a decade ago, interest in their potential applications has increased exponentially. This has been further enhanced over recent years by the discovery of methods to induce pluripotency in somatic cells, including those derived from patients with hereditary cardiac diseases. Human pluripotent stem cells have been among the most challenging cell types to grow stably in culture, but advances in reagent development now mean that most laboratories can expand both embryonic and induced pluripotent stem cells robustly using commercially available products. However, differentiation protocols have lagged behind and in many cases only produce the cell types required with low efficiency. Cardiomyocyte differentiation techniques were also initially inefficient and not readily transferable across cell lines, but there are now a number of more robust protocols available. Here, we review the basic biology underlying the differentiation of pluripotent cells to cardiac lineages and describe current state-of-the-art protocols, as well as ongoing refinements. This should provide a useful entry for laboratories new to this area to start their research. Ultimately, efficient and reliable differentiation methodologies are essential to generate desired cardiac lineages to realize the full promise of human pluripotent stem cells for biomedical research, drug development, and clinical applications.
自十年前人类胚胎干细胞首次分化为跳动的心肌细胞以来，人们对其潜在应用的兴趣呈指数级增长。近年来，包括从遗传性心脏病患者体内获取的体细胞在内的多种体细胞重编程方法的发现，进一步增强了这种兴趣。人类多能干细胞一直是培养中最难稳定生长的细胞类型之一，但试剂开发方面的进展意味着现在大多数实验室都可以使用市售产品高效地扩增胚胎干细胞和诱导多能干细胞。然而，分化方案却滞后了，在许多情况下，只能低效地产生所需的细胞类型。心肌细胞分化技术最初也效率低下，且不易在不同细胞系间转换，但现在已有许多更可靠的方案。在此，我们综述了多能细胞向心脏谱系分化的基础生物学，并描述了当前的前沿方案以及正在进行的改进。这应为该领域的新手实验室开展研究提供有益的切入点。最终，高效可靠的分化方法对于生成所需的心脏谱系至关重要，以便充分实现人类多能干细胞在生物医学研究、药物开发和临床应用中的全部潜力。
