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Nanovector-based prolyl hydroxylase domain 2 silencing system enhances the efficiency of stem cell transplantation for infarcted myocardium repair

Authors Zhu K, Lai H, Guo C, Li J, Wang Y, Wang L, Wang C

Received 23 July 2014

Accepted for publication 27 August 2014

Published 11 November 2014 Volume 2014:9(1) Pages 5203—5215

DOI https://doi.org/10.2147/IJN.S71586

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 3

Editor who approved publication: Dr Thomas J Webster

Supplementary video 1: The real-time bio-behaviors of non-transfected mesenchymal stem cells observed by Cell IQ system

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Kai Zhu,1,2 Hao Lai,1,2 Changfa Guo,1,2 Jun Li,1,2 Yulin Wang,1,2 Lingyan Wang,3 Chunsheng Wang1,2

1Department of Cardiac Surgery, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China; 2Shanghai Institute of Cardiovascular Disease, Shanghai, People’s Republic of China; 3Biomedical Research Center, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China

Abstract: Mesenchymal stem cell (MSC) transplantation has attracted much attention in myocardial infarction therapy. One of the limitations is the poor survival of grafted cells in the ischemic microenvironment. Small interfering RNA-mediated prolyl hydroxylase domain protein 2 (PHD2) silencing in MSCs holds tremendous potential to enhance their survival and paracrine effect after transplantation. However, an efficient and biocompatible PHD2 silencing system for clinical application is lacking. Herein, we developed a novel PHD2 silencing system based on arginine-terminated generation 4 poly(amidoamine) (Arg-G4) nanoparticles. The system exhibited effective and biocompatible small interfering RNA delivery and PHD2 silencing in MSCs in vitro. After genetically modified MSC transplantation in myocardial infarction models, MSC survival and paracrine function of IGF-1 were enhanced significantly in vivo. As a result, we observed decreased cardiomyocyte apoptosis, scar size, and interstitial fibrosis, and increased angiogenesis in the diseased myocardium, which ultimately attenuated ventricular remodeling and improved heart function. This work demonstrated that an Arg-G4 nanovector-based PHD2 silencing system could enhance the efficiency of MSC transplantation for infarcted myocardium repair.

Keywords: nanoparticles, PHD2, siRNA delivery, mesenchymal stem cells, myocardial infarction

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