Wu Kai Hong, Wang Su Yun, Xiao Qian Ru, Yang Yu, Huang Ning Ping, Mo Xu Ming, Sun Jian
Cardiovascular Center, Children's Hospital of Nanjing Medical University, Nanjing, China.
State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing, China.
J Cell Biochem. 2019 Feb;120(2):1318-1327. doi: 10.1002/jcb.27094. Epub 2018 Oct 14.
The purpose of this study was to investigate the cardiac-differentiation potential of induced pluripotent stem cells (iPSCs) generated from human umbilical cord-derived mesenchymal cells. Spontaneous beating colonies were observed at day 7 after the sequential addition of CHIR99021 and IWP-4. The combined use of CHIR99021 and IWP-4 downregulated the expression of pluripotency markers while upregulating cardiac transcription factors and cardiomyocyte-specific markers. The derived cardiomyocytes demonstrated typical sarcomeric structures and action-potential features; most importantly, the derived cells exhibited responsiveness to β-adrenergic and muscarinic stimulations. The analyses of molecular, structural, and functional properties revealed that the derived cardiomyocytes were similar to cardiomyocytes derived from BJ foreskin fibroblast cells. In summary, our results demonstrate that functional cardiomyocytes can be generated from human umbilical cord-derived cells. The methodology described here has potential as a means for the production of functional cardiomyocytes from discarded human umbilical cord tissue.
本研究的目的是探究从人脐带间充质细胞生成的诱导多能干细胞(iPSC)的心脏分化潜能。在依次添加CHIR99021和IWP-4后第7天观察到自发跳动的集落。CHIR99021和IWP-4联合使用下调了多能性标志物的表达,同时上调了心脏转录因子和心肌细胞特异性标志物。所产生的心肌细胞表现出典型的肌节结构和动作电位特征;最重要的是,所产生的细胞对β-肾上腺素能和毒蕈碱刺激有反应。分子、结构和功能特性分析表明,所产生的心肌细胞与源自BJ包皮成纤维细胞的心肌细胞相似。总之,我们的结果表明功能性心肌细胞可从人脐带来源的细胞产生。这里描述的方法有潜力作为从废弃人脐带组织生产功能性心肌细胞的一种手段。