微泡
间充质干细胞
归巢(生物学)
细胞生物学
骨形态发生蛋白2
干细胞
遗传增强
再生(生物学)
细胞疗法
再生医学
转染
化学
生物
小RNA
细胞培养
基因
体外
生物化学
遗传学
生态学
作者
Feiyang Li,Jun Wu,Daiye Li,Liuzhi Hao,Yanqun Li,Yi Dan,K.W.K. Yeung,Di Chen,William W. Lu,Haobo Pan,TM Wong,Xiaoli Zhao
标识
DOI:10.1186/s12951-022-01347-3
摘要
Exosomes derived from stem cells have been widely studied for promoting regeneration and reconstruction of multiple tissues as "cell-free" therapies. However, the applications of exosomes have been hindered by limited sources and insufficient therapeutic potency.In this study, a stem cell-mediated gene therapy strategy is developed in which mediator mesenchymal stem cells are genetically engineered by bone morphogenetic protein-2 gene to produce exosomes (MSC-BMP2-Exo) with enhanced bone regeneration potency. This effect is attributed to the synergistic effect of the content derived from MSCs and the up-regulated BMP2 gene expression. The MSC-BMP2-Exo also present homing ability to the injured site. The toxic effect of genetical transfection vehicles is borne by mediator MSCs, while the produced exosomes exhibit excellent biocompatibility. In addition, by plasmid tracking, it is interesting to find a portion of plasmid DNA can be encapsulated by exosomes and delivered to recipient cells.In this strategy, engineered MSCs function as cellular factories, which effectively produce exosomes with designed and enhanced therapeutic effects. The accelerating effect in bone healing and the good biocompatibility suggest the potential clinical application of this strategy.
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