Renal Regenerative Potential of Different Extracellular Vesicle Populations Derived from Bone Marrow Mesenchymal Stromal Cells.
Renal Regenerative Potential of Different Extracellular Vesicle Populations Derived from Bone Marrow Mesenchymal Stromal Cells.
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DOI：
10.1089/ten.tea.2017.0069
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发表时间：
2017-11
影响因子：
--
通讯作者：
Camussi G
中科院分区：
文献类型：
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作者：
Bruno S;Tapparo M;Collino F;Chiabotto G;Deregibus MC;Soares Lindoso R;Neri F;Kholia S;Giunti S;Wen S;Quesenberry P;Camussi G
来源于人骨髓间充质基质细胞（MSC）的细胞外囊泡（EV）以与来源细胞相当的方式促进急性肾损伤（阿基）的不同动物模型中的肾再生。然而，由于在从MSC分离的EV中观察到的异质性，尚不清楚哪个群体负责促再生效应。因此，我们评估了通过差异超离心分离的各种EV群体（富含微泡的10 K群体和富含外来体的100 K群体）对阿基恢复的影响。只有富含外泌体的人群诱导了与总EV人群相当的肾功能和形态学改善。有趣的是，在体外和体内，100 K EV对小鼠肾小管上皮细胞产生促增殖作用。对不同EV群体的分子含量的分析揭示了不同的特征。例如，100 K群体富含据报道影响细胞周期进入和进展的特定mRNA（CCNB 1，CDK 8，CDC 6）;参与调节增殖/抗凋亡途径和生长因子（肝细胞生长因子和胰岛素样生长因子-1）的miRNA，其可以解释肾小管细胞增殖的作用。另一方面，富含微泡（10 K）的EV群体不能诱导肾再生，并且具有促增殖分子表达较低的分子谱。总之，外泌体和微囊泡富集群体的不同分子组成可以解释在阿基中观察到的EV的再生效应。
Extracellular vesicles (EVs) derived from human bone marrow mesenchymal stromal cells (MSCs) promote the regeneration of kidneys in different animal models of acute kidney injury (AKI) in a manner comparable with the cells of origin. However, due to the heterogeneity observed in the EVs isolated from MSCs, it is unclear which population is responsible for the proregenerative effects. We therefore evaluated the effect of various EV populations separated by differential ultracentrifugation (10K population enriched with microvesicles and 100K population enriched with exosomes) on AKI recovery. Only the exosomal-enriched population induced an improvement of renal function and morphology comparable with that of the total EV population. Interestingly, the 100K EVs exerted a proproliferative effect on murine tubular epithelial cells, both in vitro and in vivo. Analysis of the molecular content from the different EV populations revealed a distinct profile. The 100K population, for instance, was enriched in specific mRNAs (CCNB1, CDK8, CDC6) reported to influence cell cycle entry and progression; miRNAs involved in regulating proliferative/antiapoptotic pathways and growth factors (hepatocyte growth factor and insulin-like growth factor-1) that could explain the effect of renal tubular cell proliferation. On the other hand, the EV population enriched in microvesicles (10K) was unable to induce renal regeneration and had a molecular profile with lower expression of proproliferative molecules. In conclusion, the different molecular composition of exosome- and microvesicle-enriched populations may explain the regenerative effect of EVs observed in AKI.