James Emma Claire, Tomaskovic-Crook Eva, Crook Jeremy Micah
ARC Centre of Excellence for Electromaterials Science, Intelligent Polymer Research Institute, AIIM Facility, University of Wollongong, Wollongong 2500, Australia.
Illawarra Health and Medical Research Institute, University of Wollongong, Wollongong 2500, Australia.
Int J Mol Sci. 2021 Mar 16;22(6):3005. doi: 10.3390/ijms22063005.
The regenerative capacity of cardiomyocytes is insufficient to functionally recover damaged tissue, and as such, ischaemic heart disease forms the largest proportion of cardiovascular associated deaths. Human-induced pluripotent stem cells (hiPSCs) have enormous potential for developing patient specific cardiomyocytes for modelling heart disease, patient-based cardiac toxicity testing and potentially replacement therapy. However, traditional protocols for hiPSC-derived cardiomyocytes yield mixed populations of atrial, ventricular and nodal-like cells with immature cardiac properties. New insights gleaned from embryonic heart development have progressed the precise production of subtype-specific hiPSC-derived cardiomyocytes; however, their physiological immaturity severely limits their utility as model systems and their use for drug screening and cell therapy. The long-entrenched challenges in this field are being addressed by innovative bioengingeering technologies that incorporate biophysical, biochemical and more recently biomimetic electrical cues, with the latter having the potential to be used to both direct hiPSC differentiation and augment maturation and the function of derived cardiomyocytes and cardiac tissues by mimicking endogenous electric fields.
心肌细胞的再生能力不足以在功能上修复受损组织，因此，缺血性心脏病在心血管相关死亡中占比最大。人类诱导多能干细胞（hiPSC）在开发用于心脏病建模、基于患者的心脏毒性测试以及潜在替代疗法的患者特异性心肌细胞方面具有巨大潜力。然而，传统的hiPSC衍生心肌细胞方案会产生具有不成熟心脏特性的心房、心室和节点样细胞的混合群体。从胚胎心脏发育中获得的新见解推动了亚型特异性hiPSC衍生心肌细胞的精确生产；然而，它们的生理不成熟严重限制了它们作为模型系统的效用以及它们在药物筛选和细胞治疗中的应用。该领域长期存在的挑战正通过创新的生物工程技术来解决，这些技术结合了生物物理、生化以及最近的仿生电信号，后者有可能通过模拟内源性电场来指导hiPSC分化，并增强衍生心肌细胞和心脏组织的成熟度及功能。
