Biomaterial-induced conversion of quiescent cardiomyocytes into pacemaker cells in rats

• Published in: Nature biomedical engineering Vol. 6; no. 4; pp. 421 - 434
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.04.2022; Nature Publishing Group
• Subjects: 14/19; 38/91; 631/61/54; 692/4019/592/75; 9/74; Animals; Biocompatible Materials; Biomaterials; Biomedical and Life Sciences; Biomedical Engineering/Biotechnology; Biomedical materials; Biomedicine; Cadherins; Cardiomyocytes; Cell adhesion; Cell Differentiation; Direct conversion; Ectopic expression; Endothelial cells; Fibroins - metabolism; Fibroins - pharmacology; Glycoproteins; Hydrogels; Myocytes, Cardiac; Pacemakers; Rats; Silk; Silk fibroin; Sinoatrial Node - metabolism; Stem cell transplantation; Stem cells; Surface structure; Ventricle
• ISSN: 2157-846X; 2157-846X
• DOI: 10.1038/s41551-021-00812-y

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. A silk-fibroin hydrogel converts rat quiescent ventricular cardiomyocytes into pacemaker cardiomyocytes by inducing the ectopic expression of the vascular endothelial cell-adhesion glycoprotein cadherin.