Gong Yiqi, Chen Zhuoyue, Yang Li, Ai Xuefeng, Yan Bingqian, Wang Huijing, Qiu Liya, Tan Yao, Witman Nevin, Wang Wei, Zhao Yuanjin, Fu Wei
Department of Pediatric Cardiothoracic Surgery, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, 1678 Dong Fang Road, Shanghai 200127, China.
Department of Clinical Laboratory, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008, China.
ACS Nano. 2020 Jul 28;14(7):8232-8246. doi: 10.1021/acsnano.0c01745. Epub 2020 Jul 8.
Stem-cell based differentiation for disease modeling offers great value to explore the molecular and functional underpinnings driving many types of cardiomyopathy and congenital heart diseases. Nevertheless, one major caveat in the application of differentiation of human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes (hiPSC-CMs) involves the immature phenotype of the CMs. Most of the existing methods need complex apparatus and require laborious procedures in order to monitor the cardiac differentiation/maturation process and often result in cell death. Here we developed an intrinsic color sensing system utilizing a microgroove structural color methacrylated gelatin film, which allows us to monitor the cardiac differentiation process of hiPSC-derived cardiac progenitor cells in real time. Subsequently this system can be employed as an assay system to live monitor induced functional changes on hiPSC-CMs stemming from drug treatment, the effects of which are simply revealed through color diversity. Our research shows that early intervention of cardiac differentiation through simple physical cues can enhance cardiac differentiation and maturation to some extent. Our system also simplifies the previous complex experimental processes for evaluating the physiological effects of successful differentiation and drug treatment and lays a solid foundation for future transformational applications.
基于干细胞的疾病建模分化为探索驱动多种类型心肌病和先天性心脏病的分子和功能基础提供了巨大价值。然而，人诱导多能干细胞（hiPSC）衍生的心肌细胞（hiPSC-CM）分化应用中的一个主要问题是心肌细胞的不成熟表型。现有的大多数方法需要复杂的仪器，并且在监测心脏分化/成熟过程时需要繁琐的程序，而且常常导致细胞死亡。在此，我们开发了一种利用微槽结构色甲基丙烯酸化明胶膜的内在颜色传感系统，该系统使我们能够实时监测hiPSC衍生的心脏祖细胞的心脏分化过程。随后，该系统可作为一种检测系统，用于实时监测药物治疗对hiPSC-CM诱导的功能变化，其效果可通过颜色多样性简单显示出来。我们的研究表明，通过简单的物理线索对心脏分化进行早期干预可以在一定程度上增强心脏分化和成熟。我们的系统还简化了先前用于评估成功分化和药物治疗的生理效应的复杂实验过程，并为未来的转化应用奠定了坚实基础。
