Embryonic stem cell-derived extracellular vesicles enhance the therapeutic effect of mesenchymal stem cells
Embryonic stem cell-derived extracellular vesicles enhance the therapeutic effect of mesenchymal stem cells
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胚胎干细胞来源的细胞外囊泡增强间充质干细胞的治疗效果
DOI：
10.7150/thno.35305
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发表时间：
2019
期刊：
影响因子：
12.4
通讯作者：
Cui kaige
中科院分区：
文献类型：
--
作者：
Zhang Yan;Xu Jia;Liu Siying;Lim Meikuang;Zhao Shuang;Zhang Kaiyue;Wang Lingling;Ji Qian;Han Zhongchao;Kong Deling;Li Zongjin;Liu Na;Cui kaige
背景：胚胎干细胞（ES）在再生医学中具有巨大的细胞治疗潜力。然而，伦理和安全性问题限制了其临床应用。ES衍生的细胞外囊泡（ES-EV）已被报道抑制细胞衰老。骨髓间充质干细胞（Mesenchymal stem cells，MSCs）是目前临床上广泛应用的细胞疗法。在这项研究中，我们研究了ES-EV对衰老MSC的有益作用，以进一步增强其治疗效果。研究方法：在体外，我们通过衰老相关β-gal（SA-β-gal）染色、免疫组化染色和DNA损伤灶分析来探讨ES-EV对衰老MSCs的复壮作用。通过小鼠皮肤创伤模型评价ES-EV预处理的衰老MSC的治疗效果。结果如下：我们发现ES-EV在体外显著地使衰老的MSC年轻化，并且在小鼠皮肤创伤模型中改善MSC的治疗效果。此外，我们还发现IGF 1/PI 3 K/AKT通路介导了ES-EV对MSCs的抗衰老作用。结论：结果表明，ES细胞来源的细胞外囊泡具有抗衰老的特性，能显著地使衰老的MSCs恢复活力，增强MSCs的治疗效果。这种策略可能成为MSCs临床应用的一种新的治疗策略。
Background: Embryonic stem cells (ES) have a great potential for cell-based therapies in a regenerative medicine. However, the ethical and safety issues limit its clinical application. ES-derived extracellular vesicles (ES-EVs) have been reported suppress cellular senescence. Mesenchymal stem cells (MSCs) are widely used for clinical cell therapy. In this study, we investigated the beneficial effects of ES-EVs on aging MSCs to further enhancing their therapeutic effects. Methods: In vitro, we explored the rejuvenating effects of ES-EVs on senescent MSCs by senescence-associated β-gal (SA-β-gal) staining, immunostaining, and DNA damage foci analysis. The therapeutic effect of senescent MSC pre-treated with ES-EVs was also evaluated by using mouse cutaneous wound model. Results: We found that ES-EVs significantly rejuvenated the senescent MSCs in vitro and improve the therapeutic effects of MSCs in a mouse cutaneous wound model. In addition, we also identified that the IGF1/PI3K/AKT pathway mediated the antisenescence effects of ES-EVs on MSCs. Conclusions: Our results suggested that ES cells derived-extracellular vesicles possess the antisenescence properties, which significantly rejuvenate the senescent MSCs and enhance the therapeutic effects of MSCs. This strategy might emerge as a novel therapeutic strategy for MSCs clinical application.