한빛사논문
Yoonhee Jin1,2†, Hyeok Kim3,4†, Sungjin Min1, Yi Sun Choi1, SeungJu Seo2, Eunseon Jeong1, Su Kyeom Kim1, Hyang-Ae Lee5, Sung-Hyun Jo6, Jae-Hyun Park3,4, Bong-Woo Park3,4, Woo-Sup Sim3,4, Jin-Ju Kim3,4, Kiwon Ban7, Yun-Gon Kim6, Hun-Jun Park3,4,8*, Seung-Woo Cho1,9,10*
1Department of Biotechnology, Yonsei University, Seoul 03722, Republic of Korea.
2Department of Physiology, Yonsei University College of Medicine, Seoul03722, Republic of Korea.
3Department of Biomedicine and Health Sciences, The Catholic University of Korea, Seoul 06591, Republic of Korea.
4Division of Cardiology, De-partment of Internal Medicine, Seoul St. Mary’s Hospital, The Catholic University of Korea, Seoul 06591, Republic of Korea.
5Korea Institute of Toxicology, Korea Re-search Institute of Chemical Technology, Daejeon 34114, Republic of Korea.
6Department of Chemical Engineering, Soongsil University, Seoul 06978, Republic of Korea.
7Department of Biomedical Sciences, City University of HongKong, Kowloon 999077, HongKong.
8Cell Death Disease Research Center, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea.
9Center for Nanomedicine, Institute for Basic Science(IBS), Seoul 03722,Republic of Korea.
10Graduate Program of Nano Biomedical Engineering(NanoBME), Advanced Science Institute, Yonsei University, Seoul 03722, Republic of Korea.
*Correspondingauthors : S.-W.C.; H.-J.P.
†These authors contributed equally to this work.
Abstract
Direct cardiac reprogramming has emerged as a promising therapeutic approach for cardiac regeneration. Full chemical reprogramming with small molecules to generate cardiomyocytes may be more amenable than genetic reprogramming for clinical applications as it avoids safety concerns associated with genetic manipulations. However, challenges remain regarding low conversion efficiency and incomplete cardiomyocyte maturation. Furthermore, the therapeutic potential of chemically induced cardiomyocytes (CiCMs) has not been investigated. Here, we report that a three-dimensional microenvironment reconstituted with decellularized heart extracellular matrix can enhance chemical reprogramming and cardiac maturation of fibroblasts to cardiomyocytes. The resultant CiCMs exhibit elevated cardiac marker expression, sarcomeric organization, and improved electrophysiological features and drug responses. We investigated the therapeutic potential of CiCMs reprogrammed in three-dimensional heart extracellular matrix in a rat model of myocardial infarction. Our platform can facilitate the use of CiCMs for regenerative medicine, disease modeling, and drug screening.
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