Cardiovascular Research Institute, University of California, San Francisco, CA 94143-1346, USA.
Regen Med. 2010 Sep;5(5):763-75. doi: 10.2217/rme.10.52.
Directed differentiation of human embryonic stem cells (hESCs) has generated much interest in the field of regenerative medicine. Because of their ability to differentiate into any cell type in the body, hESCs offer a novel therapeutic paradigm for myocardial repair by furnishing a supply of cardiomyocytes (CMs) that would ultimately restore normal myocardial function when delivered to the damaged heart. Spontaneous CM differentiation of hESCs is an inefficient process that yields very low numbers of CMs. In addition, it is not clear that fully differentiated CMs provide the benefits sought from cell transplantation. The need for new methods of directed differentiation of hESCs into functional CMs and cardiac progenitors has led to an explosion of research utilizing chemical, genetic, epigenetic and lineage selection strategies to direct cardiac differentiation and enrich populations of cardiac cells for therapeutic use. Here, we review these approaches and highlight their increasingly important roles in stem cell biology and cardiac regenerative medicine.
人胚胎干细胞(hESCs)的定向分化在再生医学领域引起了广泛关注。由于 hESCs 能够分化为体内任何类型的细胞,因此通过提供大量心肌细胞(CMs),当它们被输送到受损的心脏时,最终将恢复正常的心肌功能,为心肌修复提供了一种新的治疗范例。hESCs 的自发 CM 分化是一个效率低下的过程,只能产生非常少量的 CMs。此外,尚未明确完全分化的 CMs 是否能提供细胞移植所寻求的益处。需要新的方法将 hESCs 定向分化为功能性 CMs 和心脏祖细胞,这导致了利用化学、遗传、表观遗传和谱系选择策略来指导心脏分化并富集心脏细胞群体以用于治疗的研究爆炸式增长。在这里,我们综述了这些方法,并强调了它们在干细胞生物学和心脏再生医学中的日益重要作用。