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

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 Repub...

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Autores principales:	Zhu K, Lai H, Guo C, Li J, Wang Y, Wang L, Wang C
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2014
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/58d4768287014930b8f4c95bde483249
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spelling	oai:doaj.org-article:58d4768287014930b8f4c95bde4832492021-12-02T04:58:01ZNanovector-based prolyl hydroxylase domain 2 silencing system enhances the efficiency of stem cell transplantation for infarcted myocardium repair1178-2013https://doaj.org/article/58d4768287014930b8f4c95bde4832492014-11-01T00:00:00Zhttp://www.dovepress.com/nanovector-based-prolyl-hydroxylase-domain-2-silencing-system-enhances-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013 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 infarctionZhu KLai HGuo CLi JWang YWang LWang CDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2014, Iss Issue 1, Pp 5203-5215 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Zhu K Lai H Guo C Li J Wang Y Wang L Wang C Nanovector-based prolyl hydroxylase domain 2 silencing system enhances the efficiency of stem cell transplantation for infarcted myocardium repair
description	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
format	article
author	Zhu K Lai H Guo C Li J Wang Y Wang L Wang C
author_facet	Zhu K Lai H Guo C Li J Wang Y Wang L Wang C
author_sort	Zhu K
title	Nanovector-based prolyl hydroxylase domain 2 silencing system enhances the efficiency of stem cell transplantation for infarcted myocardium repair
title_short	Nanovector-based prolyl hydroxylase domain 2 silencing system enhances the efficiency of stem cell transplantation for infarcted myocardium repair
title_full	Nanovector-based prolyl hydroxylase domain 2 silencing system enhances the efficiency of stem cell transplantation for infarcted myocardium repair
title_fullStr	Nanovector-based prolyl hydroxylase domain 2 silencing system enhances the efficiency of stem cell transplantation for infarcted myocardium repair
title_full_unstemmed	Nanovector-based prolyl hydroxylase domain 2 silencing system enhances the efficiency of stem cell transplantation for infarcted myocardium repair
title_sort	nanovector-based prolyl hydroxylase domain 2 silencing system enhances the efficiency of stem cell transplantation for infarcted myocardium repair
publisher	Dove Medical Press
publishDate	2014
url	https://doaj.org/article/58d4768287014930b8f4c95bde483249
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Nanovector-based prolyl hydroxylase domain 2 silencing system enhances the efficiency of stem cell transplantation for infarcted myocardium repair

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