Stem cell-derived and circulating exosomal microRNAs as new potential tools for diabetic nephropathy management.

IF 4.4 2区 化学 Q2 MATERIALS SCIENCE, MULTIDISCIPLINARY ACS Applied Polymer Materials Pub Date : 2022-01-24 DOI:10.1186/s13287-021-02696-w
Lei Peng, Yu Chen, Shaoqing Shi, Heling Wen
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引用次数: 21

Abstract

Background: Despite major advances in the treatment of diabetic nephropathy (DN) in recent years, it remains the most common cause of end-stage renal disease. An early diagnosis and therapy may slow down the DN progression. Numerous potential biomarkers are currently being researched. Circulating levels of the kidney-released exosomes and biological molecules, which reflect the DN pathology including glomerular and tubular dysfunction as well as mesangial expansion and fibrosis, have shown the potential for predicting the occurrence and progression of DN. Moreover, many experimental therapies are currently being investigated, including stem cell therapy and medications targeting inflammatory, oxidant, or pro-fibrotic pathways activated during the DN progression. The therapeutic potential of stem cells is partly depending on their secretory capacity, particularly exosomal microRNAs (Exo-miRs). In recent years, a growing line of research has shown the participation of Exo-miRs in the pathophysiological processes of DN, which may provide effective therapeutic and biomarker tools for DN treatment.

Methods: A systematic literature search was performed in MEDLINE, Scopus, and Google Scholar to collect published findings regarding therapeutic stem cell-derived Exo-miRs for DN treatment as well as circulating Exo-miRs as potential DN-associated biomarkers.

Findings: Glomerular mesangial cells and podocytes are the most important culprits in the pathogenesis of DN and, thus, can be considered valuable therapeutic targets. Preclinical investigations have shown that stem cell-derived exosomes can exert beneficial effects in DN by transferring renoprotective miRs to the injured mesangial cells and podocytes. Of note, renoprotective Exo-miR-125a secreted by adipose-derived mesenchymal stem cells can improve the injured mesangial cells, while renoprotective Exo-miRs secreted by adipose-derived stem cells (Exo-miR-486 and Exo-miR-215-5p), human urine-derived stem cells (Exo-miR-16-5p), and bone marrow-derived mesenchymal stem cells (Exo-miR-let-7a) can improve the injured podocytes. On the other hand, clinical investigations have indicated that circulating Exo-miRs isolated from urine or serum hold great potential as promising biomarkers in DN.

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干细胞衍生和循环外泌体微小RNA作为糖尿病肾病治疗的新的潜在工具。
背景:尽管近年来糖尿病肾病(DN)的治疗取得了重大进展,但它仍然是终末期肾病最常见的病因。早期诊断和治疗可以减缓DN的进展。目前正在研究许多潜在的生物标志物。肾脏释放的外泌体和生物分子的循环水平反映了DN的病理学,包括肾小球和肾小管功能障碍以及系膜扩张和纤维化,已显示出预测DN发生和进展的潜力。此外,目前正在研究许多实验性疗法,包括干细胞疗法和针对DN进展过程中激活的炎症、氧化剂或促纤维化途径的药物。干细胞的治疗潜力部分取决于它们的分泌能力,特别是外泌体微小RNA(Exo-miRs)。近年来,越来越多的研究表明,Exo-miR参与了DN的病理生理过程,这可能为DN的治疗提供有效的治疗和生物标志物工具。方法:在MEDLINE、Scopus和Google Scholar上进行系统的文献检索,以收集已发表的关于治疗性干细胞衍生的用于DN治疗的Exo-miR以及作为潜在DN相关生物标志物的循环Exo-miRs的研究结果。研究结果:肾小球系膜细胞和足细胞是DN发病机制中最重要的罪魁祸首,因此可以被认为是有价值的治疗靶点。临床前研究表明,干细胞衍生的外泌体可以通过将肾脏保护性miR转移到受损的系膜细胞和足细胞,在DN中发挥有益作用。值得注意的是,脂肪来源的间充质干细胞分泌的肾保护性Exo-miR-125a可以改善受损的系膜细胞,而脂肪来源的干细胞(Exo-miR-486和Exo-miR-215-5p)、人尿液来源的干电池(Exo-iR-16-p)和骨髓来源的间质干细胞(Exo-miR-let-7a)分泌的肾脏保护性Exo miR可以改善受伤的足细胞。另一方面,临床研究表明,从尿液或血清中分离的循环Exo-miR作为DN的有前途的生物标志物具有很大的潜力。
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来源期刊
CiteScore
7.20
自引率
6.00%
发文量
810
期刊介绍: ACS Applied Polymer Materials is an interdisciplinary journal publishing original research covering all aspects of engineering, chemistry, physics, and biology relevant to applications of polymers. The journal is devoted to reports of new and original experimental and theoretical research of an applied nature that integrates fundamental knowledge in the areas of materials, engineering, physics, bioscience, polymer science and chemistry into important polymer applications. The journal is specifically interested in work that addresses relationships among structure, processing, morphology, chemistry, properties, and function as well as work that provide insights into mechanisms critical to the performance of the polymer for applications.
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