间充质干细胞来源细胞外囊泡治疗和修复急慢性肾损伤

Mesenchymal stem cells-derived extracellular vesicles in the treatment and repair of acute and chronic renal injuries

背景:在不同的肾损伤模型中,干细胞尤其是间充质干细胞来源细胞外囊泡具有促再生潜力。目的:文章综述了间充质干细胞来源细胞外囊泡在急性和慢性肾损伤临床前模型中的应用进展,及其在肾移植应用中的最新数据,此外讨论了提高细胞外囊泡治疗效果的新工程策略。方法:检索中国知网、万方数据和PubMed数据库,中文检索词包括“急性肾损伤、慢性肾病、细胞外囊泡、外泌体”,英文检索词包括“acute renal injury,chronic kidney disease,extracellular vesicles,exosomes,regeneration”,检索文献为研究原著和综述,检索时限为各数据库建库至2021年的相关文献,筛选82篇文献进行分析总结。结果与结论:①间充质干细胞来源细胞外囊泡在肾损伤治疗领域的研究已经广泛开展,动物实验证实间充质干细胞来源细胞外囊泡在急性和慢性肾损伤治疗中能够发挥肾脏保护作用并延缓疾病进展,具体机制涉及损伤细胞的重编程、细胞增殖和血管生成以及抑制细胞凋亡和炎症等,肾移植后立即给予细胞外囊泡可改善急性期和慢性期的缺血再灌注损伤。②有关间充质干细胞来源细胞外囊泡治疗肾病的临床试验较少,有一项临床试验观察到服用脐血间充质干细胞来源细胞外囊泡1年后,慢性肾病患者的肾功能得到了改善。③基于以上研究可见,间充质干细胞来源细胞外囊泡将有助于为急性和慢性肾损伤的有效治疗和修复等提供新的实验模型和依据,为临床治疗肾脏疾病开辟一条新的方向。

BACKGROUND:Stem cells,especially extracellular vesicles derived from mesenchymal stem cells,have the potential to promote regeneration in different renal injury models.OBJECTIVE:To review the application progress of extracellular vesicles derived from mesenchymal stem cells in preclinical models of acute and chronic renal injuries and the latest data in renal transplantation.In addition,new engineering strategies to improve the therapeutic effect of extracellular vesicles were discussed.METHODS:CNKI,Wanfang,and PubMed databases were searched.The Chinese search words included“acute renal injury,chronic kidney disease,extracellular vesicles,exosomes”.English search words included“acute renal injury,chronic kidney disease,extracellular vesicles,exosomes,regeneration”.The search literature was the original research works and reviews.The retrieval time limit was from the establishment of the database to 2021,and 82 articles were selected for analysis and summary.RESULTS AND CONCLUSION:(1)The research on mesenchymal stem cell derived extracellular vesicles in the treatment of renal injury has been widely carried out.Animal experiments have confirmed that mesenchymal stem cell derived extracellular vesicles can play a renal protective role and delay the progress of disease in the treatment of acute and chronic renal injuries.The specific mechanism involves the reprogramming of injured cells,cell proliferation,angiogenesis and inhibition of apoptosis and inflammation.Immediate administration of extracellular vesicles after renal transplantation can improve acute and chronic ischemia-reperfusion injuries.(2)There are few clinical trials on the treatment of nephropathy with mesenchymal stem cell-derived extracellular vesicles.One clinical trial observed that one year after taking umbilical cord blood mesenchymal stem cell-derived extracellular vesicles,the renal function of patients with chronic kidney disease was improved.(3)Based on the above research,mesenchymal stem cells derived extracellular vesicles will help to provide a new experimental model and basis for the effective treatment and repair of acute and chronic renal injuries,and open up a new direction for the clinical treatment of renal diseases.