Effect of Mesenchymal Stem Cell–Derived Extracellular Vesicles Induced by Advanced Glycation End Products on Energy Metabolism in Vascular Endothelial Cells

作者：Jiabin Liang, Sihang Cheng, Qi-De Song, Yukuan Tang, Qian Wang, Hanwei Chen, Jie Feng, Lin Yang, Shunli Li, Zhiwei Wang, Jinghui Fan, Chen Huang · 发表于：Kidney International Reports · 年份：2024 · DOI：10.1016/j.ekir.2024.10.015 · 被引用次数：11 · 研究领域：Extracellular vesicles in disease、Mesenchymal stem cell research、MicroRNA in disease regulation

Introduction Advanced glycation end products (AGEs) play a critical role in the development of vascular diseases in diabetes. Although stem cell therapies often involve exposure to AGEs, the impact of this environment on extracellular vesicles (EVs) and endothelial cell metabolism remains unclear. Methods Human umbilical cord mesenchymal stem cells (MSCs) were treated with either 0 ng/ml or 100 ng/ml AGEs in a serum-free medium for 48 hours, after which MSC-EVs were isolated. The EVs were characterized by morphology, particle size, and protein markers of MSC-EVs, and microRNA (miRNA) sequencing was performed to identify differentially expressed miRNAs. MSC-EVs were cocultured with human umbilical vein endothelial cells (HUVECs) to assess effects on cell viability, metabolic activity, oxidative stress, and antioxidant capacity. Tube formation and glucose transporter protein analyses were conducted to evaluate the angiogenic ability and glucose metabolism capacity. Results MSC-EVs ranged from 30 to 150 nm, which is consistent with exosomal properties. AGEs treatment reduced MSC viability but had minimal effect on EV morphology and protein markers. miRNA sequencing showed downregulation of hsa-miR-223-3p and hsa-miR-126-3p_R-1, with upregulation of hsa-miR-574-5p, implicating changes in glycolytic and oxidative phosphorylation pathways. MSC-EVs treated with AGEs decreased HUVEC viability ( P < 0.05), pH ( P < 0.05), adenosine triphosphate (ATP) metabolism ( P < 0.05), glucose me...