Mesenchymal Stem/Stromal Cell-Derived Extracellular Vesicles for Chronic Kidney Disease: Are We There Yet?
Mesenchymal Stem/Stromal Cell-Derived Extracellular Vesicles for Chronic Kidney Disease: Are We There Yet?
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DOI：
10.1161/hypertensionaha.121.14596
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发表时间：
2021-08
期刊：
影响因子：
--
通讯作者：
Lerman LO
中科院分区：
文献类型：
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作者：
Eirin A;Lerman LO
间充质干细胞/基质细胞（MSC）是细胞治疗中最常用的细胞类型，部分原因是其重要的增殖潜力和分化成各种细胞类型的能力。MSC产生大量的细胞外囊泡（EV），其携带遗传和蛋白质货物以介导MSC旁分泌功能。最近，MSC衍生的EV已成功用于几种慢性肾脏疾病的临床前模型。然而，关于EV的命运，安全性和长期影响仍然存在不确定性，这可能会对其临床转化的路径造成重要限制。这篇综述讨论了MSC衍生的EV疗法在肾脏疾病中的治疗应用，特别强调了肾脏修复的潜在机制和主要的翻译障碍。新出现的证据表明，MSC衍生的EV的货物能够调节导致肾损伤的几种途径，包括炎症、氧化应激、细胞凋亡、纤维化和微血管重塑。在实验研究中，EV诱导的这些通路的调节与重要的肾保护作用相关。然而，临床数据稀缺，当我们走向临床转化时，需要解决几个挑战，包括EV分离和表征方法的标准化，EV结局，EV效应的持续时间和心血管危险因素的影响。MSC衍生的EV具有保护肾脏结构和功能的潜力，但需要进一步的实验和临床证据来证实其对慢性肾病患者的保护作用。
Mesenchymal stem/stromal cells (MSCs) are the most utilized cell type for cellular therapy, partly due to their important proliferative potential and ability to differentiate into various cell types. MSCs produce large amounts of extracellular vesicles (EVs), which carry genetic and protein cargo to mediate MSC paracrine function. Recently, MSC-derived EVs have been successfully employed in several preclinical models of chronic kidney disease. However, uncertainty remains regarding EV fate, safety, and long-term effects, which might impose important limitations on their path to clinical translation. This review discusses the therapeutic application of MSC-derived EV therapy for renal disease, with particular emphasis on potential mechanisms of kidney repair and major translational barriers. Emerging evidence indicates that the cargo of MSC-derived EVs is capable of modulating several pathways responsible for renal injury, including inflammation, oxidative stress, apoptosis, fibrosis, and microvascular remodeling. EV-induced modulation of these pathways has been associated with important renoprotective effects in experimental studies. However, scarce clinical data are available, and several challenges need to be addressed as we move towards clinical translation, including standardization of methods for EV isolation and characterization, EV fate, duration of EV effects, and effects of cardiovascular risk factors. MSC-derived EVs have potential to preserve renal structure and function, but further experimental and clinical evidence is needed to confirm their protective effects in patients with chronic kidney disease.