Nanoparticle-enhanced generation of gene-transfected mesenchymal stem cells for in聽vivo cardiac repair

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• 作者：Kai Zhu^a ; ^b ; ¹ ; Meiying Wu^c ; ¹ ; Hao Lai^a ; ^b ; Changfa Guo^a ; ^b ; Jun Li^a ; ^b ; Yulin Wang^a ; ^b ; Yu Chen^c ; ^{chenyu@mail.sic.ac.cn" class="auth_mail" title="E-mail the corresponding author} ; Chunsheng Wang^a ; ^b ; ^{wang.chunsheng@zs-hospital.sh.cn" class="auth_mail" title="E-mail the corresponding author} ; Jianlin Shi^c ; ^{jlshi@mail.sic.ac.cn" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Large mesopore ; Mesoporous organosilica ; Gene transfection ; Stem-cell therapy ; Cardiac repair
• 刊名：Biomaterials
• 出版年：2016
• 出版时间：January 2016
• 年：2016
• 卷：74
• 期：Complete
• 页码：188-199
• 全文大小：2728 K

文摘

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.