诱导多能干细胞-骨髓基质细胞来源的大型细胞外囊泡通过 ERK/MAPK 增强肢体血管生成。

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

机构信息

Institute of Microsurgery on Extremities, Department of Orthopedic Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 600# Yishan Road, Shanghai 200233, China.

Department of Orthopedic Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 600# Yishan Road, Shanghai 200233, China.

出版信息

Nanomedicine (Lond). 2024 Jul 14;19(17):1525-1539. doi: 10.1080/17435889.2024.2363743. Epub 2024 Jul 16.

DOI:10.1080/17435889.2024.2363743

PMID:39012207

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11321421/

Abstract

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. The pathology of muscles was accessed by H&E staining and immunofluorescence staining. , we conducted wound-healing assay, tube formation assay, RT qPCR, ELISA, RNA sequencing and proteomic analysis. iMSCs-lEVs alleviated the injury of ischemic lower limb and promoted the recovery of lower limb function. , iMSCs-lEVs promoted the proliferation, migration, and angiogenesis of HMEC-1 cells by regulating the ERK/MAPK signing pathway. This study demonstrated that iMSCs-lEVs promoted endothelial cell angiogenesis via the ERK/MAPK signaling pathway, thereby improving function after lower limb ischemic injury.

摘要

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，并探讨其潜在机制。通过 H&E 染色和免疫荧光染色评估肌肉病理学变化。我们进行了划痕愈合实验、管形成实验、RT-qPCR、ELISA、RNA 测序和蛋白质组学分析。结果表明，iMSCs-lEVs 减轻了缺血性下肢的损伤，并促进了下肢功能的恢复。此外，iMSCs-lEVs 通过调节 ERK/MAPK 信号通路促进了 HMEC-1 细胞的增殖、迁移和血管生成。本研究表明，iMSCs-lEVs 通过 ERK/MAPK 信号通路促进内皮细胞血管生成，从而改善下肢缺血损伤后的功能。