An <i>in Vivo</i> miRNA Delivery System for Restoring Infarcted Myocardium.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 31149806.
- Also identified by DOI 10.1021/acsnano.9b03343 and PMC identifier 7930012.
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Abstract
A major challenge in myocardial infarction (MI)-related heart failure treatment using microRNA is the efficient and sustainable delivery of miRNAs into myocardium to achieve functional improvement through stimulation of intrinsic myocardial restoration. In this study, we established an <i>in vivo</i> delivery system using polymeric nanoparticles to carry miRNA (miNPs) for localized delivery within a shear-thinning injectable hydrogel. The miNPs triggered proliferation of human embryonic stem cell-derived cardiomyocytes and endothelial cells (hESC-CMs and hESC-ECs) and promoted angiogenesis in hypoxic conditions, showing significantly lower cytotoxicity than Lipofectamine. Furthermore, one injected dose of hydrogel/miNP in MI rats demonstrated significantly improved cardiac functions: increased ejection fraction from 45% to 64%, reduced scar size from 20% to 10%, and doubled capillary density in the border zone compared to the control group at 4 weeks. As such, our results indicate that this injectable hydrogel/miNP composite can deliver miRNA to restore injured myocardium efficiently and safely.
Medical subject headings
- Gene Transfer Techniques
- MicroRNAs
- Myocardial Infarction