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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

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

Neural regeneration research, 2025-02, Vol.20 (2), p.518-532 [Periódico revisado por pares]

India: Wolters Kluwer Medknow Publications

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  • Título:
    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
  • Autor: Wang, Conglin ; Cheng, Fangyuan ; Han, Zhaoli ; Yan, Bo ; Liao, Pan ; Yin, Zhenyu ; Ge, Xintong ; Li, Dai ; Zhong, Rongrong ; Liu, Qiang ; Chen, Fanglian ; Lei, Ping
  • Assuntos: akt ; astrocyte ; blood–brain barrier ; cerebral edema ; exosomes ; human-induced pluripotent stem cells ; intracerebral hemorrhage ; neural stem cells ; neuroinflammation ; pi3k
  • É parte de: Neural regeneration research, 2025-02, Vol.20 (2), p.518-532
  • Notas: ObjectType-Article-1
    SourceType-Scholarly Journals-1
    ObjectType-Feature-2
    content type line 23
  • Descrição: JOURNAL/nrgr/04.03/01300535-202502000-00029/figure1/v/2024-05-28T214302Z/r/image-tiff Cerebral edema caused by blood-brain barrier injury after intracerebral hemorrhage is an important factor leading to poor prognosis. Human-induced pluripotent stem cell-derived neural stem cell exosomes (hiPSC-NSC-Exos) have shown potential for brain injury repair in central nervous system diseases. In this study, we explored the impact of hiPSC-NSC-Exos on blood-brain barrier preservation and the underlying mechanism. Our 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 hemorrhage. Additionally, 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-α post-intracerebral hemorrhage, thereby improving the inflammatory microenvironment. RNA 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 integrity. Treatment with the PI3K/AKT inhibitor LY294002 or the monocyte chemoattractant protein-1 neutralizing agent C1142 abolished these effects. In 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.
  • Editor: India: Wolters Kluwer Medknow Publications
  • Idioma: Inglês
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  • Realização: ABCD-USP USP   Logos de Redes Sociais: Freepik

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