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Human-induced pluripotent stem cell-derived neural stem cell exosomes improve blood-brain barrier function after intracerebral hemorrhage by activating astrocytes via PI3K/AKT/MCP-1 axis

作     者:Conglin Wang Fangyuan Cheng Zhaoli Han Bo Yan Pan Liao Zhenyu Yin Xintong Ge Dai Li Rongrong Zhong Qiang Liu Fanglian Chen Ping Lei Conglin Wang;Fangyuan Cheng;Zhaoli Han;Bo Yan;Pan Liao;Zhenyu Yin;Xintong Ge;Dai Li;Rongrong Zhong;Qiang Liu;Fanglian Chen;Ping Lei

作者机构:Department of GeriatricsTianjin Medical University General HospitalTianjinChina School of MedicineNankai UniversityTianjinChina Tianjin Neurological InstituteTianjinChina 

出 版 物:《Neural Regeneration Research》 (中国神经再生研究(英文版))

年 卷 期:2025年第20卷第2期

页      面:518-532页

核心收录:

学科分类:1002[医学-临床医学] 100204[医学-神经病学] 10[医学] 

基  金:supported by the National Natural Science Foundation of China,No.8227050826(to PL) Tianjin Science and Technology Bureau Foundation,No.20201194(to PL) Tianjin Graduate Research and Innovation Project,No.2022BKY174(to CW) 

主  题:AKT astrocyte blood-brain barrier cerebral edema exosomes human-induced pluripotent stem cells intracerebral hemorrhage neural stem cells neuroinflammation PI3K 

摘      要:Cerebral edema caused by blood-brain barrier injury after intracerebral hemorrhage is an important factor leading to poor ***-induced pluripotent stem cell-derived neural stem cell exosomes(hiPSC-NSC-Exos)have shown potential for brain injury repair in central nervous system *** this study,we explored the impact of hiPSC-NSC-Exos on blood-brain barrier preservation and the underlying *** results indicated that intranasal delivery of hiPSC-NSC-Exos mitigated neurological deficits,enhanced blood-brain barrier integrity,and reduced leukocyte infiltration in a mouse model of intracerebral ***,hiPSC-NSC-Exos decreased immune cell infiltration,activated astrocytes,and decreased the secretion of inflammatory cytokines like monocyte chemoattractant protein-1,macrophage inflammatory protein-1α,and tumor necrosis factor-αpost-intracerebral hemorrhage,thereby improving the inflammatory *** sequencing indicated that hiPSC-NSC-Exo activated the PI3K/AKT signaling pathway in astrocytes and decreased monocyte chemoattractant protein-1 secretion,thereby improving blood-brain barrier *** with the PI3K/AKT inhibitor LY294002 or the monocyte chemoattractant protein-1 neutralizing agent C1142 abolished these *** summary,our findings suggest that hiPSC-NSC-Exos maintains blood-brain barrier integrity,in part by downregulating monocyte chemoattractant protein-1 secretion through activation of the PI3K/AKT signaling pathway in astrocytes.

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