Large extracellular vesicles from induced pluripotent stem cell-marrow stem cells enhance limb angiogenesis via ERK/MAPK.

Nanomedicine (London, England) Pub Date : 2024-07-14 Epub Date: 2024-07-16 DOI:10.1080/17435889.2024.2363743
Ziyu Huang, Zhengsheng Chen, Teng Ye, Lei Luo, Juntao Zhang, Qing Li, Yang Wang, Bizeng Zhao
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Abstract

Aim: This study aims to investigate the effects of large extracellular vesicles (EVs) induced by pluripotent stem cell-derived mesenchymal stem cells on lower limb ischemic disease and explore its potential mechanisms. Materials & methods: The pathology of muscles was accessed by H&E staining and immunofluorescence staining. In vitro, we conducted wound-healing assay, tube formation assay, RT qPCR, ELISA, RNA sequencing and proteomic analysis. Results: iMSCs-lEVs alleviated the injury of ischemic lower limb and promoted the recovery of lower limb function. In vitro, iMSCs-lEVs promoted the proliferation, migration, and angiogenesis of HMEC-1 cells by regulating the ERK/MAPK signing pathway. Conclusion: This study demonstrated that iMSCs-lEVs promoted endothelial cell angiogenesis via the ERK/MAPK signaling pathway, thereby improving function after lower limb ischemic injury.

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诱导多能干细胞-骨髓干细胞的大细胞外囊泡通过ERK/MAPK促进肢体血管生成。
目的:本研究旨在探讨多能干细胞衍生的间充质干细胞诱导的大细胞外囊泡(EVs)对下肢缺血性疾病的影响及其潜在机制。材料与方法:通过H&E染色和免疫荧光染色观察肌肉的病理变化。在体外,我们进行了伤口愈合试验、管形成试验、RT qPCR、ELISA、RNA测序和蛋白质组分析。结果:iMSCs-lEVs能减轻缺血下肢的损伤,促进下肢功能的恢复。在体外,iMSCs-lEVs 通过调节 ERK/MAPK 信号通路促进 HMEC-1 细胞的增殖、迁移和血管生成。结论本研究表明,iMSCs-lEVs 可通过 ERK/MAPK 信号通路促进内皮细胞血管生成,从而改善下肢缺血性损伤后的功能。
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