Nat Biomed Eng. 2021 Nov 22; doi: 10.1038/s41551-021-00812-y. Epub 2021 Nov 22.

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

Nature biomedical engineering

Yu-Feng Hu, An-Sheng Lee, Shih-Lin Chang, Shien-Fong Lin, Ching-Hui Weng, Hsin-Yu Lo, Pei-Chun Chou, Yung-Nan Tsai, Yen-Ling Sung, Chien-Chang Chen, Ruey-Bing Yang, Yuh-Charn Lin, Terry B J Kuo, Cheng-Han Wu, Jin-Dian Liu, Tze-Wen Chung, Shih-Ann Chen

PMID: 34811487 DOI: 10.1038/s41551-021-00812-y

Abstract

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.

© 2021. The Author(s), under exclusive licence to Springer Nature Limited.

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Publication Types

• Journal Article

Grant support

• 105-2633-B-075-002, 107-2628-B-075-003, 108-2628-B-075-003, 107-2221-E-010-005-MY3/Ministry of Science and Technology, Taiwan (Ministry of Science and Technology of Taiwan)
• NHRI-EX108-10513SC/National Health Research Institutes (NHRI)
• AS-TM-109-01-05, AS-TM-110-01-01/Academia Sinica