Division of Nephrology and Hypertension, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA.
Stem Cell Res Ther. 2017 Dec 4;8(1):273. doi: 10.1186/s13287-017-0727-7.
Novel therapies are urgently needed to address the rising incidence and prevalence of acute kidney injury (AKI) and chronic kidney disease (CKD). Mesenchymal stem/stromal cells (MSCs) have shown promising results in experimental AKI and CKD, and have been used in the clinic for more than a decade with an excellent safety profile. The regenerative effects of MSCs do not rely on their differentiation and ability to replace damaged tissues, but are primarily mediated by the paracrine release of factors, including extracellular vesicles (EVs), composed of microvesicles and exosomes. MSC-derived EVs contain genetic and protein material that upon transferring to recipient cells can activate several repair mechanisms to ameliorate renal injury. Recent studies have shown that MSC-derived EV therapy improved renal outcomes in several animal models of AKI and CKD, including ischemia-reperfusion injury, drug/toxin-induced nephropathy, renovascular disease, ureteral obstruction, and subtotal nephrectomy. However, data about the renoprotective effects of EV therapy in patients with renal failure are scarce. This review summarizes current knowledge of MSC-derived EV therapy in experimental AKI and CKD, and discusses the challenges that need to be addressed in order to consider MSC-derived EVs as a realistic clinical tool to treat patients with these conditions.
急需新的治疗方法来应对急性肾损伤 (AKI) 和慢性肾脏病 (CKD) 的发病率和患病率不断上升的问题。间充质干细胞 (MSCs) 在实验性 AKI 和 CKD 中显示出很有前景的结果，并已在临床上使用了十多年，具有极好的安全性。MSCs 的再生作用不依赖于它们的分化和替代受损组织的能力，而是主要通过旁分泌释放包括细胞外囊泡 (EVs) 在内的多种因子来介导，EVs 由微泡和外泌体组成。MSC 衍生的 EV 含有遗传和蛋白质物质，转移到受体细胞后可以激活几种修复机制来改善肾损伤。最近的研究表明，MSC 衍生的 EV 治疗在几种 AKI 和 CKD 的动物模型中改善了肾脏结局，包括缺血再灌注损伤、药物/毒素诱导的肾病、肾血管疾病、输尿管梗阻和部分肾切除术。然而，关于 EV 治疗在肾衰竭患者中的肾脏保护作用的数据很少。这篇综述总结了目前关于 MSC 衍生的 EV 在实验性 AKI 和 CKD 中的治疗作用的知识，并讨论了为将 MSC 衍生的 EV 作为治疗这些疾病患者的现实临床工具而需要解决的挑战。
