Versatile human cardiac tissues engineered with perfusable heart extracellular microenvironment for biomedical applications

Sungjin Min, Suran Kim, Woo-Sup Sim, Yi Sun Choi, Hyebin Joo, Jae-Hyun Park, Su-Jin Lee, Hyeok Kim, Mi Jeong Lee, Inhea Jeong, Baofang Cui, Sung-Hyun Jo, Jin-Ju Kim, Seok Beom Hong, Yeon-Jik Choi, Kiwon Ban, Yun-Gon Kim, Jang-Ung Park, Hyang-Ae Lee, Hun-Jun Park () and Seung-Woo Cho ()
Additional contact information
Sungjin Min: Yonsei University
Suran Kim: Yonsei University
Woo-Sup Sim: College of Medicine, The Catholic University of Korea
Yi Sun Choi: Yonsei University
Hyebin Joo: Yonsei University
Jae-Hyun Park: College of Medicine, The Catholic University of Korea
Su-Jin Lee: Korea Institute of Toxicology
Hyeok Kim: College of Medicine, The Catholic University of Korea
Mi Jeong Lee: Yonsei University
Inhea Jeong: Yonsei University
Baofang Cui: Yonsei University
Sung-Hyun Jo: Soongsil University
Jin-Ju Kim: College of Medicine, The Catholic University of Korea
Seok Beom Hong: Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea
Yeon-Jik Choi: Eunpyeong St. Mary’s Hospital, College of Medicine, The Catholic University of Korea
Kiwon Ban: City University of Hong Kong
Yun-Gon Kim: Soongsil University
Jang-Ung Park: Yonsei University
Hyang-Ae Lee: Korea Institute of Toxicology
Hun-Jun Park: College of Medicine, The Catholic University of Korea
Seung-Woo Cho: Yonsei University

Nature Communications, 2024, vol. 15, issue 1, 1-22

Abstract: Abstract Engineered human cardiac tissues have been utilized for various biomedical applications, including drug testing, disease modeling, and regenerative medicine. However, the applications of cardiac tissues derived from human pluripotent stem cells are often limited due to their immaturity and lack of functionality. Therefore, in this study, we establish a perfusable culture system based on in vivo-like heart microenvironments to improve human cardiac tissue fabrication. The integrated culture platform of a microfluidic chip and a three-dimensional heart extracellular matrix enhances human cardiac tissue development and their structural and functional maturation. These tissues are comprised of cardiovascular lineage cells, including cardiomyocytes and cardiac fibroblasts derived from human induced pluripotent stem cells, as well as vascular endothelial cells. The resultant macroscale human cardiac tissues exhibit improved efficacy in drug testing (small molecules with various levels of arrhythmia risk), disease modeling (Long QT Syndrome and cardiac fibrosis), and regenerative therapy (myocardial infarction treatment). Therefore, our culture system can serve as a highly effective tissue-engineering platform to provide human cardiac tissues for versatile biomedical applications.

Date: 2024
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DOI: 10.1038/s41467-024-46928-y

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