MicroRNA-containing extracellular vesicles released from endothelial colony-forming cells modulate angiogenesis during ischaemic retinopathy.
MicroRNA-containing extracellular vesicles released from endothelial colony-forming cells modulate angiogenesis during ischaemic retinopathy.
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DOI：
10.1111/jcmm.13251
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发表时间：
2017-12
影响因子：
5.3
通讯作者：
Simpson DA
中科院分区：
文献类型：
--
作者：
Dellett M;Brown ED;Guduric-Fuchs J;O'Connor A;Stitt AW;Medina RJ;Simpson DA
内皮集落形成细胞（ECFC）是内皮祖细胞的一种定义亚型，可调节血管修复并促进缺血组织的灌注。它们对驻留脉管系统的旁分泌活性不明确，但至少部分由细胞外囊泡（EV）的转移介导。为了评估分离的EV为基于细胞的疗法提供替代方案的潜力，我们首先对ECFC释放的EV进行了物理和分子表征。在增殖性视网膜病变模型中评估了它们对体外内皮细胞和体内血管生成的影响。EV表达典型的标志物CD9和CD63，并通过电子显微镜形成大小为约60至1500 nm的异质群体。ECFC EV被内皮细胞吸收并增加细胞迁移。微阵列分析反映了这一点，显示与血管生成相关的基因表达发生了显著变化。对ECFC及其EV中的小RNA进行测序表明，多种microRNA在EV中高度表达并集中。这些微小RNA的预测靶基因显着丰富的功能类别包括血管生成。玻璃体内递送的ECFC EV与血管系统相关，并显著减少了小鼠氧诱导视网膜病变模型中的无血管面积。我们的研究结果证实了分离的EV影响内皮细胞功能并作为调节血管生成的疗法的潜力。与ECFC EV中检测到的特定microRNA相关的功能支持microRNA转移在介导观察到的效应中的作用。
Endothelial colony‐forming cells (ECFCs) are a defined subtype of endothelial progenitors that modulate vascular repair and promote perfusion in ischaemic tissues. Their paracrine activity on resident vasculature is ill‐defined, but mediated, at least in part, by the transfer of extracellular vesicles (EVs). To evaluate the potential of isolated EVs to provide an alternative to cell‐based therapies, we first performed a physical and molecular characterization of those released by ECFCs. Their effects upon endothelial cells in vitro and angiogenesis in vivo in a model of proliferative retinopathy were assessed. The EVs expressed typical markers CD9 and CD63 and formed a heterogeneous population ranging in size from ~60 to 1500 nm by electron microscopy. ECFC EVs were taken up by endothelial cells and increased cell migration. This was reflected by microarray analyses which showed significant changes in expression of genes associated with angiogenesis. Sequencing of small RNAs in ECFCs and their EVs showed that multiple microRNAs are highly expressed and concentrated in EVs. The functional categories significantly enriched for the predicted target genes of these microRNAs included angiogenesis. Intravitreally delivered ECFC EVs were associated with the vasculature and significantly reduced the avascular area in a mouse oxygen‐induced retinopathy model. Our findings confirm the potential of isolated EVs to influence endothelial cell function and act as a therapy to modulate angiogenesis. The functions associated with the specific microRNAs detected in ECFC EVs support a role for microRNA transfer in mediating the observed effects.
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影响因子：
16
作者：
Lötvall J;Hill AF;Hochberg F;Buzás EI;Di Vizio D;Gardiner C;Gho YS;Kurochkin IV;Mathivanan S;Quesenberry P;Sahoo S;Tahara H;Wauben MH;Witwer KW;Théry C
通讯作者：
Théry C
影响因子：
7.3
作者：
Andreu Z;Yáñez-Mó M
通讯作者：
Yáñez-Mó M
DOI：
10.1073/pnas.1521230113
发表时间：
2016-02-23
影响因子：
11.1
作者：
Kowal, Joanna;Arras, Guillaume;Thery, Clotilde
通讯作者：
Thery, Clotilde
影响因子：
16
作者：
Crescitelli R;Lässer C;Szabó TG;Kittel A;Eldh M;Dianzani I;Buzás EI;Lötvall J
通讯作者：
Lötvall J
DOI：
10.1073/pnas.1405388111
发表时间：
2014-07-15
影响因子：
11.1
作者：
Lin, Ruei-Zeng;Moreno-Luna, Rafael;Melero-Martin, Juan M.
通讯作者：
Melero-Martin, Juan M.