Three-dimensional heart extracellular matrix enhances chemically induced direct cardiac reprogramming

Yoonhee Jin, Hyeok Kim, Sungjin Min, Yi Sun Choi, Seung Ju Seo, Eunseon Jeong, Su Kyeom Kim, Hyang Ae Lee, Sung Hyun Jo, Jae Hyun Park, Bong Woo Park, Woo Sup Sim, Jin Ju Kim, Kiwon Ban, Yun Gon Kim, Hun Jun Park, Seung Woo Cho

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Article numberabn5768
JournalScience Advances
Issue number50
Publication statusPublished - 2022 Dec

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© 2022 The Authors.

All Science Journal Classification (ASJC) codes

  • General


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