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Updated: Jun 18, 2025
Isolation, Characterization, and Therapeutic Application of Extracellular Vesicles from Cultured Human Mesenchymal Stem Cells
Published on: September 23, 2022
Mesenchymal stem cell-derived extracellular vesicles ameliorate renal interstitial fibrosis via the miR-13474/ADAM17
Linru Shi1,2, Yuyan Hu2,3, Houcheng Zeng2
1Center for Molecular & Imageology of Jiangsu University, Division of Nephrology, The Affiliated Yixing Hospital of Jiangsu University, Yixing, 214200, Jiangsu, China.
Abstract:
Renal interstitial fibrosis (RIF) is a prevalent consequence of chronic renal diseases, characterized by excessive extracellular matrix (ECM) deposition. A Disintegrin and Metalloprotease 17 (ADAM17), a transmembrane metalloproteinase, plays a central role in driving renal fibrosis progression by activating Notch 1 protein and the downstream TGF-β signaling pathway. Our study investigated potential therapeutic interventions for renal fibrosis, focusing on human umbilical cord mesenchymal stem cell-derived extracellular vesicles (hucMSC-EVs). We found that hucMSC-EVs inhibit ADAM17, thereby impeding renal fibrosis progression. Analysis of hucMSC-EVs miRNA profiles revealed significant enrichment of miR-13474, which effectively targeted and inhibited ADAM17 mRNA expression, subsequently suppressing Notch1 activation, TGF-β signaling, and collagen deposition. Overexpression of miR-13474 enhanced hucMSC-EVs' inhibitory effect on renal fibrosis, while its downregulation abolished this protective effect. Our findings highlight the efficacy of hucMSC-EVs overexpressing miR-13474 in mitigating renal fibrosis via ADAM17 targeting. These insights offer potential therapeutic strategies for managing renal fibrosis.
Insights
Human umbilical cord mesenchymal stem cell-derived extracellular vesicles (hucMSC-EVs) show promise for treating renal interstitial fibrosis. These EVs inhibit ADAM17, a key driver of fibrosis, through miR-13474, offering a novel therapeutic strategy.
Area of Science:
- Nephrology
- Cell Biology
- Biochemistry
Background:
- Renal interstitial fibrosis (RIF) involves excessive extracellular matrix deposition, a common outcome of chronic kidney diseases.
- A Disintegrin and Metalloprotease 17 (ADAM17) is crucial in RIF progression by activating Notch 1 and TGF-β signaling.
Purpose of the Study:
- To investigate human umbilical cord mesenchymal stem cell-derived extracellular vesicles (hucMSC-EVs) as a potential therapy for RIF.
- To elucidate the mechanism by which hucMSC-EVs mitigate renal fibrosis.
Main Methods:
- Analysis of hucMSC-EVs' effect on ADAM17 and downstream signaling pathways in RIF models.
- miRNA profiling of hucMSC-EVs to identify key regulatory molecules.
- Genetic manipulation of miR-13474 levels in hucMSC-EVs to assess its role in fibrosis inhibition.
Main Results:
- hucMSC-EVs were found to inhibit ADAM17, thereby reducing renal fibrosis.
- miR-13474 was significantly enriched in hucMSC-EVs and directly targeted ADAM17 mRNA.
- Overexpression of miR-13474 enhanced the antifibrotic effects of hucMSC-EVs, while downregulation abolished them.
Conclusions:
- hucMSC-EVs, particularly those overexpressing miR-13474, effectively mitigate renal fibrosis by targeting ADAM17.
- This study presents a novel therapeutic strategy for renal fibrosis management using engineered hucMSC-EVs.
