title: Nanoparticle-enhanced generation of gene-transfected mesenchymal stem cells for in vivo cardiac repair.
abstract: Transplantation of gene-transfected bone marrow-derived mesenchymal stem cells (BMMSCs) is a promising strategy for ischemic myocardium repair, but current therapeutic strategy suffers from high toxicity and inefficient gene transfection in primary BMMSCs. Here we designed and synthesized molecularly organic-inorganic hybrid hollow mesoporous organosilica nanoparticles (HMONs) based on nano-synthetic chemistry, which are featured with concurrent large pore size over 20 nm, small particulate size, hollow cavity and high dispersity for gene transfection in BMMSCs and subsequent in vivo cardiac repair. To efficiently create the therapeutic gene-transfected stem-cell lines, hepatocyte growth factor (HGF) gene was applied to transfect BMMSCs via biocompatible surface-engineered HMONs as a high-performance gene-delivery nanosystem. On the rat model of myocardial infarction, transplantation of HGF gene-transfected BMMSCs enables the largely decreased apoptotic cardiomyocytes, reduced infarct scar size, relieved interstitial fibrosis, and increased angiogenesis in myocardium. The resultant cardiac repair further promotes the significant improvement of heart function. Therefore, the fabricated organic-inorganic hybrid HMONs with large pore size represent a generalizable strategy and platform for gene transfection in BMMSCs and further regenerative medicine.
authors.affiliation: Department of Cardiac Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, PR China; Shanghai Institute of Cardiovascular Disease, Shanghai 200032, PR China.
authors.forename: Kai
authors.initials: K
authors.lastname: Zhu
authors.affiliation: State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai 200050, PR China.
authors.forename: Meiying
authors.initials: M
authors.lastname: Wu
authors.affiliation: Department of Cardiac Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, PR China; Shanghai Institute of Cardiovascular Disease, Shanghai 200032, PR China.
authors.forename: Hao
authors.initials: H
authors.lastname: Lai
authors.affiliation: Department of Cardiac Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, PR China; Shanghai Institute of Cardiovascular Disease, Shanghai 200032, PR China.
authors.forename: Changfa
authors.initials: C
authors.lastname: Guo
authors.affiliation: Department of Cardiac Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, PR China; Shanghai Institute of Cardiovascular Disease, Shanghai 200032, PR China.
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Cardiac Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, PR China; Shanghai Institute of Cardiovascular Disease, Shanghai 200032, PR China.
authors.forename: Yulin
authors.initials: Y
authors.lastname: Wang
authors.affiliation: State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai 200050, PR China. Electronic address: chenyu@mail.sic.ac.cn.
authors.forename: Yu
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Cardiac Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, PR China; Shanghai Institute of Cardiovascular Disease, Shanghai 200032, PR China. Electronic address: wang.chunsheng@zs-hospital.sh.cn.
authors.forename: Chunsheng
authors.initials: C
authors.lastname: Wang
authors.affiliation: State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai 200050, PR China. Electronic address: jlshi@mail.sic.ac.cn.
authors.forename: Jianlin
authors.initials: J
authors.lastname: Shi
mesh_terms: D001672:Biocompatible Materials; D006321:Heart / Q000502:physiology*; D017228:Hepatocyte Growth Factor / Q000235:genetics; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D053758:Nanoparticles; D014162:Transfection
chemical_list: D001672:Biocompatible Materials; D017228:Hepatocyte Growth Factor
keywords: Cardiac repair; Gene transfection; Large mesopore; Mesoporous organosilica; Stem-cell therapy