Published online Dec 26, 2019. doi: 10.4252/wjsc.v11.i12.1130
Peer-review started: June 19, 2019
First decision: July 31, 2019
Revised: September 23, 2019
Accepted: October 14, 2019
Article in press: October 14, 2019
Published online: December 26, 2019
After myocardial infarction (MI) in adults, the regenerative ability of the differentiated cardiomyocytes is very limited due to the “terminated” cell proliferative ability and the lack of cardiac stem cells. Tissue repair after pathological injury in the heart, including that after MI, is still a major clinical challenge. Two novel strategies have been suggested to restore the lost cardiomyocytes caused by MI. One is to apply cardiomyocytes differentiated from stem cells or derived from cardiospheres, and the other is to induce cell cycle reentry in cardiomyocytes.
Stem cells and stem cell-derived cardiomyocytes have been demonstrated to be a promising source for cell transplantation-based treatment of injured hearts. Modification of approaches to induce cardiac cell differentiation from stem cells with high efficiency will be crucial to improve the therapeutic effect.
To explore the function of miR-301a in regulating cardiomyocyte differentiation of mouse embryonic stem cells, and provide experimental evidence for applying miR-301a to the cardiomyocyte differentiation induction from stem cells.
The hanging drop technique was applied to form embryoid bodies from mouse embryonic stem cells with or without overexpression of miR-301a. Cardiac markers including GATA-4, TBX5, and MEF2C, and α-actinin were used to determine cardiomyocyte differentiation from mouse embryonic stem cells.
MiR-301a was identified as a miRNA highly enriched in the heart from late embryonic to neonatal mice. Overexpression of miR-301a in mouse embryonic stem cells significantly induced the expression of cardiac transcription factors, thereby promoting cardiomyocyte differentiation and beating cardiomyocyte clone formation. PTEN was demonstrated to be a target gene of miR-301a in cardiomyocytes. PTEN-regulated AKT-mTOR-Stat3 signaling was involved in regulation of miR-301a-induced cardiomyocyte differentiation.
MiR-301a is capable of promoting embryonic stem cell differentiation to cardiomyocytes. As such, miR-301a has potential as a novel target gene to induce cardiomyocyte differentiation.
These findings will be beneficial in development of an approach with high efficiency to induce stem cell differentiation to cardiomyocytes, and strengthen the potential of cell therapeutics to treat heart failure caused by myocardial infarction.