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

Cho, Jaeyeaon and Kim, Sangsung and Lee, Hyein and Rah, Woongchan and Cho, Hee Cheol and Kim, Nam Kyun and Bae, Seongho and Shin, Dong Hoon and Lee, Min Goo and Park, In-Hyun and Tanaka, Yoshiaki and Shin, Eric and Yi, Hong and Han, Ji Woong and Hwang, Patrick Tae Joon and Jun, Ho-Wook and Park, Hun-Jun and Cho, Kyuwon and Lee, Sang Wook and Jung, Jae Kyung and Levit, Rebecca D. and Sussman, Mark A. and Harvey, Richard P. and Yoon, Young-sup (2021) Regeneration of infarcted mouse hearts by cardiovascular tissue formed via the direct reprogramming of mouse fibroblasts. Nature Biomedical Engineering, 5 (8). pp.880-896. ISSN 2157-846X

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Link to published document: http://doi.org/10.1038/s41551-021-00783-0

Abstract

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.

Item Type: Article
Subjects: R Medicine > R Medicine (General)
Depositing User: Repository Administrator
Date Deposited: 30 Sep 2021 02:24
Last Modified: 30 Sep 2021 02:24
URI: http://eprints.victorchang.edu.au/id/eprint/1118

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