Hu Yu-Feng, Lee An-Sheng, Chang Shih-Lin, Lin Shien-Fong, Weng Ching-Hui, Lo Hsin-Yu, Chou Pei-Chun, Tsai Yung-Nan, Sung Yen-Ling, Chen Chien-Chang, Yang Ruey-Bing, Lin Yuh-Charn, Kuo Terry B J, Wu Cheng-Han, Liu Jin-Dian, Chung Tze-Wen, Chen Shih-Ann
Heart Rhythm Center, Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
Faculty of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
Nat Biomed Eng. 2022 Apr;6(4):421-434. doi: 10.1038/s41551-021-00812-y. Epub 2021 Nov 22.
Pacemaker cells can be differentiated from stem cells or transdifferentiated from quiescent mature cardiac cells via genetic manipulation. Here we show that the exposure of rat quiescent ventricular cardiomyocytes to a silk-fibroin hydrogel activates the direct conversion of the quiescent cardiomyocytes to pacemaker cardiomyocytes by inducing the ectopic expression of the vascular endothelial cell-adhesion glycoprotein cadherin. The silk-fibroin-induced pacemaker cells exhibited functional and morphological features of genuine sinoatrial-node cardiomyocytes in vitro, and pacemaker cells generated via the injection of silk fibroin in the left ventricles of rats functioned as a surrogate in situ sinoatrial node. Biomaterials with suitable surface structure, mechanics and biochemistry could facilitate the scalable production of biological pacemakers for human use.
通过基因操作，起搏细胞可与干细胞区分开来，或从静止的成熟心肌细胞转分化而来。在此，我们表明，将大鼠静止的心室心肌细胞暴露于丝素蛋白水凝胶中，通过诱导血管内皮细胞粘附糖蛋白钙粘蛋白的异位表达，可激活静止心肌细胞直接转化为起搏心肌细胞。丝素蛋白诱导产生的起搏细胞在体外表现出真正窦房结心肌细胞的功能和形态特征，并且通过向大鼠左心室注射丝素蛋白产生的起搏细胞在原位起到了替代窦房结的作用。具有合适表面结构、力学性能和生物化学性质的生物材料可促进用于人类的生物起搏器的规模化生产。
