Cho et al., Nature Biomedical Engineering, 2021

Nat Biomed Eng. 2021 Aug;5(8):880-896. doi: 10.1038/s41551-021-00783-0. Epub 2021 Aug 23.

Regeneration of infarcted mouse hearts by cardiovascular tissue formed via the direct reprogramming of mouse fibroblasts

Jaeyeaon Cho 1 2Sangsung Kim 2Hyein Lee 2Woongchan Rah 2Hee Cheol Cho 3Nam Kyun Kim 3Seongho Bae 1Dong Hoon Shin 2Min Goo Lee 4In-Hyun Park 5Yoshiaki Tanaka 6Eric Shin 1Hong Yi 7Ji Woong Han 1Patrick Tae Joon Hwang 8Ho-Wook Jun 8Hun-Jun Park 9Kyuwon Cho 1Sang Wook Lee 1Jae Kyung Jung 1Rebecca D Levit 1Mark A Sussman 10 11Richard P Harvey 12Young-Sup Yoon 13 14


Fibroblasts can be directly reprogrammed into cardiomyocytes, endothelial cells or smooth muscle cells. Here we report the reprogramming of mouse tail-tip fibroblasts simultaneously into cells resembling these three cell types using the microRNA mimic miR-208b-3p, ascorbic acid and bone morphogenetic protein 4, as well as the formation of tissue-like structures formed by the directly reprogrammed cells. Implantation of the formed cardiovascular tissue into the infarcted hearts of mice led to the migration of reprogrammed cells to the injured tissue, reducing regional cardiac strain and improving cardiac function. The migrated endothelial cells and smooth muscle cells contributed to vessel formation, and the migrated cardiomyocytes, which initially displayed immature characteristics, became mature over time and formed gap junctions with host cardiomyocytes. Direct reprogramming of somatic cells to make cardiac tissue may aid the development of applications in cell therapy, disease modelling and drug discovery for cardiovascular diseases.

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Categories: 2021