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Regeneration of infarcted mouse hearts by cardiovascular tissue formed via the direct reprogramming of mouse fibroblasts
- Source :
- Nat Biomed Eng
- Publication Year :
- 2021
- Publisher :
- Springer Science and Business Media LLC, 2021.
-
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 via 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 into 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.
- Subjects :
- Cell type
Somatic cell
Myocytes, Smooth Muscle
Myocardial Infarction
Biomedical Engineering
Neovascularization, Physiologic
Medicine (miscellaneous)
Bioengineering
Ascorbic Acid
Bone Morphogenetic Protein 4
Article
Mice
microRNA
Animals
Regeneration
Myosin Heavy Chains
Chemistry
Myocardium
Regeneration (biology)
Gap junction
Endothelial Cells
Gap Junctions
Heart
Fibroblasts
Cellular Reprogramming
Ascorbic acid
Computer Science Applications
Cell biology
Mice, Inbred C57BL
MicroRNAs
Bone morphogenetic protein 4
Transcriptome
Reprogramming
Biotechnology
Subjects
Details
- ISSN :
- 2157846X
- Volume :
- 5
- Database :
- OpenAIRE
- Journal :
- Nature Biomedical Engineering
- Accession number :
- edsair.doi.dedup.....1fb248ac5d4805ad64286697491fef95