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

Jaeyeaon Cho, Sangsung Kim, Hyein Lee, Woongchan Rah, Hee Cheol Cho, Nam Kyun Kim, Seongho Bae, Dong Hoon Shin, Min Goo Lee, In Hyun Park, Yoshiaki Tanaka, Eric Shin, Hong Yi, Ji Woong Han, Patrick Tae Joon Hwang, Ho Wook Jun, Hun Jun Park, Kyuwon Cho, Sang Wook Lee, Jae Kyung JungRebecca D. Levit, Mark A. Sussman, Richard P. Harvey, Young sup Yoon

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)880-896
Number of pages17
JournalNature biomedical engineering
Issue number8
Publication statusPublished - 2021 Aug

Bibliographical note

Funding Information:
We thank J. V. Taylor for sample preparations for TEM images and J. Mobley at the University of Alabama at Birmingham Comprehensive Cancer Center Mass Spectrometry/Proteomics Shared Facility for LC–MS analysis. This work was supported by grants from the National Heart, Lung, and Blood Institute (R01HL150877, R61HL154116, R01HL129511 and R01HL125391), an American Heart Association Transformative Project Award and the Bio and Medical Technology Development Program of the National Research Foundation grant funded by the Korean government (MSIT) (2020M3A9I4038454, 2020R1A2C3003784 and 2017R1D1A1B03036063).

Publisher Copyright:
© 2021, The Author(s), under exclusive licence to Springer Nature Limited.

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Bioengineering
  • Medicine (miscellaneous)
  • Biomedical Engineering
  • Computer Science Applications


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