间充质干细胞
旁分泌信号
再生医学
细胞生物学
干细胞
细胞外小泡
血管生成
细胞外
细胞疗法
胞外囊泡
癌症研究
再生(生物学)
生物医学工程
微泡
生物
医学
生物化学
小RNA
基因
受体
作者
Xianyun Wang,Shiqi Hu,Junlang Li,Dashuai Zhu,Zhenzhen Wang,Jhon Cores,Ke Cheng,Gang Liu
标识
DOI:10.1021/acsami.1c08044
摘要
Mesenchymal stem cells (MSCs) repair injured tissues mainly through their paracrine actions. One of the important paracrine components of MSC secretomes is the extracellular vesicle (EV). The therapeutic potential of MSC-EVs has been established in various cardiac injury preclinical models. However, the large-scale production of EVs remains a challenge. We sought to develop a scale-up friendly method to generate a large number of therapeutic nanovesicles from MSCs by extrusion. Those extruded nanovesicles (NVs) are miniature versions of MSCs in terms of surface marker expression. The yield of NVs is 20-fold more than that of EVs. In vitro, cell-based assays demonstrated the myocardial protective effects and therapeutic potential of NVs. Intramyocardial delivery of NVs in the injured heart after ischemia-reperfusion led to a reduction in scar sizes and preservation of cardiac functions. Such therapeutic benefits are similar to those injected with natural EVs from the same MSC parental cells. In addition, NV therapy promoted angiogenesis and proliferation of cardiomyocytes in the post-injury heart. In summary, extrusion is a highly efficient method to generate a large quantity of therapeutic NVs that can potentially replace extracellular vesicles in regenerative medicine applications.
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