Human embryonic stem cells and cardiac repair.
Human embryonic stem cells and cardiac repair.
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DOI：
10.1016/j.trre.2008.05.005
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发表时间：
2009-01-01
期刊：
影响因子：
--
通讯作者：
Laflamme, Michael A
中科院分区：
文献类型：
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作者：
Zhu, Wei-Zhong;Hauch, Kip D;Laflamme, Michael A
心肌梗塞后失去的肌肉被非收缩性疤痕组织所取代，通常会引发心力衰竭。全器官心脏移植是目前唯一可用的替代丢失肌肉的临床手段，但这种选择受到供体心脏供应不足的限制。因此，基于细胞的心脏修复作为改善心脏损伤的替代方法引起了相当大的兴趣。由于其巨大的扩增能力和无可争议的心脏潜力，多能人胚胎干细胞（hESC）代表了一种有吸引力的候选细胞来源，可用于获得心肌细胞和其他有用的间充质细胞类型以进行此类治疗。人类胚胎干细胞衍生的心肌细胞表现出定型心脏表型和强大的增殖能力，最近在啮齿动物梗塞模型中的测试表明它们可以使受损的心脏部分重新肌肉化并改善收缩功能。尽管后者的成功令人有充分的理由乐观，但在成功应用 hESC 进行心脏修复方面仍然存在相当大的挑战，包括需要高心脏纯度的制剂、改进的递送方法以及克服免疫排斥和移植细胞死亡的其他原因的方法。本综述将描述 hESC 衍生的心肌细胞的表型和这些细胞的临床前经验，并将考虑克服上述挑战的策略。
The muscle lost after a myocardial infarction is replaced with noncontractile scar tissue, often initiating heart failure. Whole-organ cardiac transplantation is the only currently available clinical means of replacing the lost muscle, but this option is limited by the inadequate supply of donor hearts. Thus, cell-based cardiac repair has attracted considerable interest as an alternative means of ameliorating cardiac injury. Because of their tremendous capacity for expansion and unquestioned cardiac potential, pluripotent human embryonic stem cells (hESCs) represent an attractive candidate cell source for obtaining cardiomyocytes and other useful mesenchymal cell types for such therapies. Human embryonic stem cell-derived cardiomyocytes exhibit a committed cardiac phenotype and robust proliferative capacity, and recent testing in rodent infarct models indicates that they can partially remuscularize injured hearts and improve contractile function. Although the latter successes give good reason for optimism, considerable challenges remain in the successful application of hESCs to cardiac repair, including the need for preparations of high cardiac purity, improved methods of delivery, and approaches to overcome immune rejection and other causes of graft cell death. This review will describe the phenotype of hESC-derived cardiomyocytes and preclinical experience with these cells and will consider strategies to overcoming the aforementioned challenges.