An in Vivo miRNA Delivery System for Restoring Infarcted Myocardium. ACS Nano 2019 Sep 24;13(9):9880-9894
Date
06/01/2019Pubmed ID
31149806Pubmed Central ID
PMC7930012DOI
10.1021/acsnano.9b03343Scopus ID
2-s2.0-85067391864 (requires institutional sign-in at Scopus site) 121 CitationsAbstract
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.
Author List
Yang H, Qin X, Wang H, Zhao X, Liu Y, Wo HT, Liu C, Nishiga M, Chen H, Ge J, Sayed N, Abilez OJ, Ding D, Heilshorn SC, Li KAuthor
Chun Liu PhD Assistant Professor in the Physiology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsCell Death
Cell Hypoxia
Cell Proliferation
Gene Expression Regulation
Gene Transfer Techniques
Human Embryonic Stem Cells
Humans
Hydrogels
Injections
MicroRNAs
Myocardial Infarction
Myocytes, Cardiac
Nanoparticles
Rats
Reperfusion Injury
