Extracellular vesicles derived from human bone marrow mesenchymal stem cells promote angiogenesis in a rat myocardial infarction model
Extracellular vesicles derived from human bone marrow mesenchymal stem cells promote angiogenesis in a rat myocardial infarction model
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人骨髓间充质干细胞来源的细胞外囊泡促进大鼠心肌梗死模型中的血管生成
DOI：
10.1007/s00109-013-1110-5
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发表时间：
2014-04-01
影响因子：
4.7
通讯作者：
Yu, Hepeng
中科院分区：
文献类型：
--
作者：
Bian, Suyan;Zhang, Liping;Yu, Hepeng
间充质干细胞（MSC）已越来越多地在实验和临床上用于心脏修复。然而，由于梗死心肌中移植细胞的存活率低和大量死亡，其潜在机制仍存在争议。最近的报道表明，由MSC释放的细胞外囊泡（EV）具有促进血管生成的活性;然而，MSC-EV对缺血心脏的治疗效果尚不清楚。在本研究中，我们报道了MSC在缺氧刺激下可以释放大量直径约100 nm的EV，尽管大多数细胞没有经历凋亡。人脐静脉内皮细胞可迅速摄取MSC-EVs，并呈剂量依赖性地促进内皮细胞的体外增殖、迁移和管腔形成。使用急性心肌梗死大鼠模型，我们发现，与PBS治疗相比，心肌内注射MSC-EV显著增强了血流恢复，与梗死面积减少和心脏收缩和舒张性能保持一致。这些数据表明，与MSC一样，MSC-EV也可以至少通过促进血管形成来保护心脏组织免受缺血性损伤，但应进行进一步详细的研究以确定MSC-EV的功能。
Mesenchymal stem cells (MSCs) have been increasingly tested experimentally and clinically for cardiac repair. However, the underlying mechanisms remain controversial due to the poor viability and considerable death of the engrafted cells in the infracted myocardium. Recent reports have suggested that extracellular vesicles (EVs) released by MSCs have angiogenesis-promoting activity; however, the therapeutic effect of MSC-EVs on an ischemic heart is unclear. In the present study, we reported that MSCs could release a large quantity of EVs around 100 nm in diameter upon hypoxia stimulation though the majority of the cells had not experienced apoptosis. MSC-EVs could be promptly uptaken by human umbilical vein endothelial cells, and the internalization resulted in dose-dependent enhancement of in vitro proliferation, migration, and tube formation of endothelial cells. Using an acute myocardial infarction rat model, we found that intramyocardial injection of MSC-EVs markedly enhanced blood flow recovery, in accordance with reduced infarct size and preserved cardiac systolic and diastolic performance compared to those treated with PBS. These data suggest that like MSCs, MSC-EVs could also protect cardiac tissue from ischemic injury at least by means of promoting blood vessel formation, though further detailed investigations should be performed to define the functionality of MSC-EVs.