Mesenchymal stem cells-extracellular vesicles alleviate pulmonary fibrosis by regulating immunomodulators  

作　　者：Ying Gao Mei-Fang Liu Yang Li Xi Liu Yu-Jie Cao Qian-Fa Long Jun Yu Jian-Ying Li 

机构地区：[1]Department of Respiratory and Critical Care Medicine,Shaanxi Provincial Rehabilitation Hospital,Xi’an 710000,Shaanxi Province,China [2]Department of Respiratory and Critical Care Medicine,Second Affiliated Hospital of Ningxia Medical University(The First People’s Hospital of Yinchuan),Yinchuan 750001,Ningxia Hui Autonomous Region,China [3]School of Clinical Medicine,Xi’an Medical University,Xi’an 710021,Shaanxi Province,China [4]Department of Respiratory and Critical Care Medicine,Xi’an Central Hospital,Xi’an 710000,Shaanxi Province,China [5]Department of Neurosurgery,Xi’an Central Hospital,Xi’an 710000,Shaanxi Province,China [6]Department of Emergency,Xi’an Central Hospital,Xi’an 710000,Shaanxi Province,China

出　　处：《World Journal of Stem Cells》2024年第6期670-689,共20页世界干细胞杂志（英文版）（电子版）

基　　金：Supported by Xi’an Science and Technology Plan Project,No.20200001YX001(1);Xi’an Talent Plan-Elite(Innovative Talents)Project,No.XAYC210062.

摘　　要：BACKGROUND Pulmonary fibrosis(PF)is a chronic interstitial lung disease characterized by fibroblast proliferation and extracellular matrix formation,causing structural damage and lung failure.Stem cell therapy and mesenchymal stem cells-extracellular vesicles(MSC-EVs)offer new hope for PF treatment.AIM To investigate the therapeutic potential of MSC-EVs in alleviating fibrosis,oxidative stress,and immune inflammation in A549 cells and bleomycin(BLM)-induced mouse model.METHODS The effect of MSC-EVs on A549 cells was assessed by fibrosis markers[collagen I andα-smooth muscle actin(α-SMA),oxidative stress regulators[nuclear factor E2-related factor 2(Nrf2)and heme oxygenase-1(HO-1),and inflammatory regu-lators[nuclear factor-kappaB(NF-κB)p65,interleukin(IL)-1β,and IL-2].Similarly,they were assessed in the lungs of mice where PF was induced by BLM after MSC-EV transfection.MSC-EVs ion PF mice were detected by pathological staining and western blot.Single-cell RNA sequencing was performed to investigate the effects of the MSC-EVs on gene expression profiles of macrophages after modeling in mice.RESULTS Transforming growth factor(TGF)-β1 enhanced fibrosis in A549 cells,significantly increasing collagen I andα-SMA levels.Notably,treatment with MSC-EVs demonstrated a remarkable alleviation of these effects.Similarly,the expression of oxidative stress regulators,such as Nrf2 and HO-1,along with inflammatory regulators,including NF-κB p65 and IL-1β,were mitigated by MSC-EV treatment.Furthermore,in a parallel manner,MSC-EVs exhibited a downregulatory impact on collagen deposition,oxidative stress injuries,and inflammatory-related cytokines in the lungs of mice with PF.Additionally,the mRNA sequencing results suggested that BLM may induce PF in mice by upregulating pulmonary collagen fiber deposition and triggering an immune inflammatory response.The findings collectively highlight the potential therapeutic efficacy of MSC-EVs in ameliorating fibrotic processes,oxidative stress,and inflammatory responses associated

关 键 词：Mesenchymal stem cells Extracellular vesicles Pulmonary fibrosis Oxidative stress response Epithelial-mesenchymal transition 

分 类 号：R563[医药卫生—呼吸系统]