Department of Bioengineering, University of California, San Diego, CA, USA.
Wiley Interdiscip Rev Syst Biol Med. 2011 Nov-Dec;3(6):666-80. doi: 10.1002/wsbm.141. Epub 2010 Dec 31.
Cardiovascular disease remains the leading cause of death in the Western world and myocardial infarction is one of the primary facets of this disease. The limited natural self-renewal of cardiac muscle following injury and restricted supply of heart transplants has encouraged researchers to investigate other means to stimulate regeneration of damaged myocardium. The plasticity of stem cells toward multiple lineages offers the potential to repair the heart following injury. Embryonic stem cells have been extensively studied for their ability to differentiate into early cardiomyocytes, however, the pathway has only been partially defined and inadequate efficiency limits their clinical applicability. Some studies have shown cardiomyogenesis from adult mesenchymal stem cells, from both bone marrow and adipose tissue, but their differentiation pathway remains poorly detailed and these results remain controversial. Despite promising results using stem cells in animal models of cardiac injury, the driving mechanisms behind their differentiation down a cardiomyogenic pathway have yet to be determined. Currently, there is a paucity of information regarding cardiomyogenesis on the systemic level. Stem cell differentiation results from multiple signaling parameters operating in a tightly regulated spatiotemporal pattern. Investigating this phenomenon from a systems biology perspective could unveil the abstruse mechanisms controlling cardiomyogenesis that would otherwise require extensive in vitro testing.
心血管疾病仍然是西方世界的主要死亡原因,心肌梗死是这种疾病的主要表现之一。受伤后心肌的有限自然自我更新和心脏移植的供应有限,促使研究人员探索其他刺激受损心肌再生的方法。干细胞向多个谱系的可塑性为受伤后的心脏修复提供了潜力。胚胎干细胞因其能够分化为早期心肌细胞的能力而被广泛研究,然而,该途径仅部分定义,效率不足限制了其临床适用性。一些研究表明,骨髓和脂肪组织来源的成体间充质干细胞具有心肌发生能力,但它们的分化途径仍不清楚,这些结果仍存在争议。尽管在心脏损伤的动物模型中使用干细胞取得了有希望的结果,但它们向心肌生成途径分化的驱动机制仍有待确定。目前,关于系统水平上的心肌发生的信息很少。干细胞分化是由多个信号参数在严格调节的时空模式下共同作用的结果。从系统生物学的角度研究这一现象,可以揭示控制心肌发生的深奥机制,而这些机制在体外需要进行广泛的测试。