| Literature DB >> 31149806 |
Huaxiao Yang1, Xulei Qin1, Huiyuan Wang2, Xin Zhao1, Yonggang Liu1, Hung-Ta Wo1, Chun Liu1, Masataka Nishiga1, Haodong Chen1, Jing Ge3, Nazish Sayed1, Oscar J Abilez1, Dan Ding4, Sarah C Heilshorn2, Kai Li3,5.
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 in vivo 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.Entities:
Keywords: cardiovascular disease; conjugated polymer; gene delivery; myocardial infarction; regenerative medicine
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Year: 2019 PMID： 31149806 PMCID： PMC7930012 DOI： 10.1021/acsnano.9b03343
Source DB: PubMed Journal: ACS Nano ISSN： 1936-0851 Impact factor: 15.881