Umbilical Cord Mesenchymal Stem Cell-Derived Extracellular Vesicles as Natural Nanocarriers in the Treatment of Nephrotoxic Injury In Vitro.

IF 5.1 2区生物学 Q2 CELL BIOLOGY Cells Pub Date : 2024-10-07 DOI:10.3390/cells13191658

Márcia Bastos Convento, Andreia Silva de Oliveira, Mirian Aparecida Boim, Fernanda Teixeira Borges

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Abstract

Umbilical cord mesenchymal stem cell-derived extracellular vesicles (UC-EVs) are valuable in nanomedicine as natural nanocarriers, carrying information molecules from their parent cells and fusing with targeted cells. miRNA-126, specific to endothelial cells and derived from these vesicles, supports vascular integrity and angiogenesis and has protective effects in kidney diseases.

Objective: This study investigates the delivery of miRNA-126 and anti-miRNA-126 via UC-EVs as natural nanocarriers for treating nephrotoxic injury in vitro.

Method: The umbilical cord-derived mesenchymal stem cell and UC-EVs were characterized according to specific guidelines. Rat kidney proximal tubular epithelial cells (tubular cells) were exposed to nephrotoxic injury through of gentamicin and simultaneously treated with UC-EVs carrying miRNA-126 or anti-miRNA-126. Specific molecules that manage cell cycle progression, proliferation cell assays, and newly synthesized DNA and DNA damage markers were evaluated.

Results: We observed significant increases in the expression of cell cycle markers, including PCNA, p53, and p21, indicating a positive cell cycle regulation with newly synthesized DNA via BrDU. The treatments reduced the expression of DNA damage marker, such as H2Ax, suggesting a lower rate of cellular damage.

Conclusions: The UC-EVs, acting as natural nanocarriers of miRNA-126 and anti-miRNA-126, offer nephroprotective effects in vitro. Additionally, other components in UC-EVs, such as proteins, lipids, and various RNAs, might also contribute to these effects.

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脐带间充质干细胞衍生的细胞外囊泡是治疗体外肾毒性损伤的天然纳米载体

脐带间充质干细胞衍生的细胞外囊泡（UC-EVs）作为天然纳米载体，携带母细胞的信息分子并与目标细胞融合，在纳米医学中具有重要价值。miRNA-126对内皮细胞具有特异性，从这些囊泡中提取，支持血管完整性和血管生成，对肾脏疾病具有保护作用：本研究探讨了通过天然纳米载体 UC-EV 传递 miRNA-126 和抗 miRNA-126，以治疗体外肾毒性损伤：方法：根据特定指南对脐带间充质干细胞和UC-EV进行表征。将大鼠肾近曲小管上皮细胞（肾小管细胞）暴露于庆大霉素的肾毒性损伤中，同时用携带miRNA-126或抗miRNA-126的UC-EVs进行处理。对管理细胞周期进展的特定分子、增殖细胞检测、新合成的 DNA 和 DNA 损伤标记物进行了评估：结果：我们观察到细胞周期标志物（包括 PCNA、p53 和 p21）的表达明显增加，这表明新合成的 DNA 通过 BrDU 对细胞周期起到了积极的调节作用。这些处理降低了 DNA 损伤标志物（如 H2Ax）的表达，表明细胞损伤率降低：UC-EV作为miRNA-126和抗miRNA-126的天然纳米载体，在体外具有保护肾脏的作用。此外，UC-EV 中的其他成分，如蛋白质、脂类和各种 RNA，也可能有助于产生这些效果。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cells Biochemistry, Genetics and Molecular Biology-Biochemistry, Genetics and Molecular Biology (all)

CiteScore

9.90

自引率

5.00%

发文量

3472

审稿时长

16 days

期刊介绍： Cells (ISSN 2073-4409) is an international, peer-reviewed open access journal which provides an advanced forum for studies related to cell biology, molecular biology and biophysics. It publishes reviews, research articles, communications and technical notes. Our aim is to encourage scientists to publish their experimental and theoretical results in as much detail as possible. There is no restriction on the length of the papers. Full experimental and/or methodical details must be provided.