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<p>This study aims to investigate the effect of exosomes derived from olfactory mucosa mesenchymal stem cells (OM-MSCs-Exo) on microglial polarization and its potential therapeutic role in Alzheimer’s disease (AD). OM-MSCs-Exo were isolated and purified from the mice olfactory mucosa, followed by phenotypic characterization. Proteins transferred by OM-MSCs-Exo were screened using proteomic analysis. The AD model was established in microglial cells and mice with Aβ<sub>1–42</sub>. Immunofluorescence and biochemical assays were employed to assess the impact of OM-MSCs-Exo and its secreted protein FGFR1 on microglial polarization. Protein–protein interactions and immunoprecipitation were used to identify the target proteins of FGFR1 in microglial cells. Additionally, the effects of OM-MSCs-Exo-induced microglial polarization on neuronal inflammation and cognitive function in mice were evaluated. OM-MSCs-Exo were successfully isolated and purified. FGFR1 was significantly upregulated in OM-MSCs-Exo compared to OM-MSCs. Aβ<sub>1–42</sub> induced M1 polarization and suppressed M2 polarization of microglia, which was reversed by OM-MSCs-Exo. FGFR1 overexpression in OM-MSCs-Exo further enhanced M2 polarization in microglial cells. Phospholipase C gamma 1 (PLCγ1) was identified as the target of FGFR1, and knocking down PLCγ1 reversed the effects of FGFR1-overexpressing OM-MSCs-Exo. OM-MSCs-Exo alleviated cognitive decline and neuroinflammation in AD mice, with FGFR1 overexpression further enhancing these effects. OM-MSCs-Exo promote M2 polarization of microglia in AD mice through the FGFR1/PLCγ1 pathway, alleviating neuronal inflammation and cognitive dysfunction.</p>

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Olfactory Mucosa Mesenchymal Stem Cell–Derived Exosomes Enhance Microglia M2 Polarization via the FGFR1/PLCγ1 Axis to Alleviate Alzheimer’s Disease

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年1月1日

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  • Ya-nan Ma,
  • Zijie Wang,
  • Yuchang Liang,
  • Guoao Tan,
  • Xiqi Hu,
  • Ying Xia

摘要

This study aims to investigate the effect of exosomes derived from olfactory mucosa mesenchymal stem cells (OM-MSCs-Exo) on microglial polarization and its potential therapeutic role in Alzheimer’s disease (AD). OM-MSCs-Exo were isolated and purified from the mice olfactory mucosa, followed by phenotypic characterization. Proteins transferred by OM-MSCs-Exo were screened using proteomic analysis. The AD model was established in microglial cells and mice with Aβ1–42. Immunofluorescence and biochemical assays were employed to assess the impact of OM-MSCs-Exo and its secreted protein FGFR1 on microglial polarization. Protein–protein interactions and immunoprecipitation were used to identify the target proteins of FGFR1 in microglial cells. Additionally, the effects of OM-MSCs-Exo-induced microglial polarization on neuronal inflammation and cognitive function in mice were evaluated. OM-MSCs-Exo were successfully isolated and purified. FGFR1 was significantly upregulated in OM-MSCs-Exo compared to OM-MSCs. Aβ1–42 induced M1 polarization and suppressed M2 polarization of microglia, which was reversed by OM-MSCs-Exo. FGFR1 overexpression in OM-MSCs-Exo further enhanced M2 polarization in microglial cells. Phospholipase C gamma 1 (PLCγ1) was identified as the target of FGFR1, and knocking down PLCγ1 reversed the effects of FGFR1-overexpressing OM-MSCs-Exo. OM-MSCs-Exo alleviated cognitive decline and neuroinflammation in AD mice, with FGFR1 overexpression further enhancing these effects. OM-MSCs-Exo promote M2 polarization of microglia in AD mice through the FGFR1/PLCγ1 pathway, alleviating neuronal inflammation and cognitive dysfunction.