Division of Cardiology, Department of Medicine, University of Illinois at Chicago, Chicago, IL 60612, USA.
Department of Bioengineering, University of Illinois at Chicago, Chicago, IL 60607, USA.
Exp Biol Med (Maywood). 2021 Aug;246(16):1816-1828. doi: 10.1177/15353702211009146. Epub 2021 Apr 25.
Induced pluripotent stem cells (iPSCs) serve as a robust platform to model several human arrhythmia syndromes including atrial fibrillation (AF). However, the structural, molecular, functional, and electrophysiological parameters of patient-specific iPSC-derived atrial cardiomyocytes (iPSC-aCMs) do not fully recapitulate the mature phenotype of their human adult counterparts. The use of physiologically inspired microenvironmental cues, such as postnatal factors, metabolic conditioning, extracellular matrix (ECM) modulation, electrical and mechanical stimulation, co-culture with non-parenchymal cells, and 3D culture techniques can help mimic natural atrial development and induce a more mature adult phenotype in iPSC-aCMs. Such advances will not only elucidate the underlying pathophysiological mechanisms of AF, but also identify and assess novel mechanism-based therapies towards supporting a more 'personalized' (i.e. patient-specific) approach to pharmacologic therapy of AF.
诱导多能干细胞 (iPSC) 可作为一个强大的平台，用于模拟多种人类心律失常综合征，包括心房颤动 (AF)。然而，患者特异性 iPSC 衍生的心房肌细胞 (iPSC-aCM) 的结构、分子、功能和电生理参数并不能完全再现其成人对应物的成熟表型。使用生理上有启发性的微环境线索，如产后因素、代谢调节、细胞外基质 (ECM) 调节、电和机械刺激、与非实质细胞共培养以及 3D 培养技术，有助于模拟自然心房发育，并在 iPSC-aCM 中诱导更成熟的成年表型。这些进展不仅将阐明 AF 的潜在病理生理机制，还将确定和评估基于新机制的治疗方法，以支持更“个体化”（即患者特异性）的 AF 药物治疗方法。
