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Circulating re-entrant waves promote maturation of hiPSC-derived cardiomyocytes in self-organized tissue ring
Communications Biology ( IF 5.9 ) Pub Date : 2020-03-13 , DOI: 10.1038/s42003-020-0853-0
Junjun Li , Lu Zhang , Leqian Yu , Itsunari Minami , Shigeru Miyagawa , Marcel Hörning , Ji Dong , Jing Qiao , Xiang Qu , Ying Hua , Nanae Fujimoto , Yuji Shiba , Yang Zhao , Fuchou Tang , Yong Chen , Yoshiki Sawa , Chao Tang , Li Liu

Directed differentiation methods allow acquisition of high-purity cardiomyocytes differentiated from human induced pluripotent stem cells (hiPSCs); however, their immaturity characteristic limits their application for drug screening and regenerative therapy. The rapid electrical pacing of cardiomyocytes has been used for efficiently promoting the maturation of cardiomyocytes, here we describe a simple device in modified culture plate on which hiPSC-derived cardiomyocytes can form three-dimensional self-organized tissue rings (SOTRs). Using calcium imaging, we show that within the ring, reentrant waves (ReWs) of action potential spontaneously originated and ran robustly at a frequency up to 4 Hz. After 2 weeks, SOTRs with ReWs show higher maturation including structural organization, increased cardiac-specific gene expression, enhanced Ca2+-handling properties, an increased oxygen-consumption rate, and enhanced contractile force. We subsequently use a mathematical model to interpret the origination, propagation, and long-term behavior of the ReWs within the SOTRs.



中文翻译:

循环折返波促进自组织组织环中hiPSC衍生的心肌细胞的成熟

定向分化方法可以采集从人诱导多能干细胞(hiPSC)分化出的高纯度心肌细胞;然而,它们的不成熟特性限制了它们在药物筛选和再生疗法中的应用。心肌细胞的快速电起搏已用于有效促进心肌细胞的成熟,在这里我们描述了一种改良的培养板中的简单设备,hiPSC衍生的心肌细胞可以在其上形成三维自组织组织环(SOTR)。使用钙成像,我们显示在环内,动作电位的折返波(ReWs)自发地产生并以高达4 Hz的频率强劲运行。2周后,具有ReWs的SOTRs表现出更高的成熟度,包括结构组织,增加的心脏特异性基因表达,增强的Ca2+处理性能,增加的耗氧率和增强的收缩力。随后,我们使用数学模型来解释SOW中ReW的起源,传播和长期行为。

更新日期:2020-03-16
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