論文 - 詳細
| RRC ID | 86441 |
|---|---|
| 著者 | Lin SL, Chang YW, Lee W, Chiang CS, Liu SP, Lee HT, Jeng LB, Shyu WC. |
| タイトル | Role of STAT3-FOXO3 Signaling in the Modulation of Neuroplasticity by PD-L1-HGF-Decorated Mesenchymal Stem Cell-Derived Exosomes in a Murine Stroke Model. |
| ジャーナル | Adv Sci (Weinh) |
| Abstract |
The limited therapeutic strategies available for stroke leave many patients disabled for life. This study assessed the potential of programmed death-ligand 1 (PD-L1) and hepatocyte growth factor (HGF)-engineered mesenchymal stem cell-derived exosomes (EXO-PD-L1-HGF) in enhancing neurological recovery post-stroke. EXO-PD-L1-HGF, which efficiently endocytosed into target cells, significantly diminishes the H2O2-induced neurotoxicity and increased the antiapoptotic proteins in vitro. EXO-PD-L1-HGF attenuates inflammation by inhibiting T-cell proliferation and increasing the number of CD8+CD122+IL-10+ regulatory T cells. Intravenous injection of EXO-PD-L1-HGF could target stromal cell-derived factor-1α (SDF-1α+) cells over the peri-infarcted area of the ischemic brain through CXCR4 upregulation and accumulation in neuroglial cells post-stroke. EXO-PD-L1-HGF facilitates endogenous nestin+ neural progenitor cell (NPC)-induced neurogenesis via STAT3-FOXO3 signaling cascade, which plays a pivotal role in cell survival and neuroprotection, thereby mitigating infarct size and enhancing neurological recovery in a murine stroke model. Moreover, increasing populations of the immune-regulatory CD19+IL-10+ and CD8+CD122+IL-10+ cells, together with reducing populations of proinflammatory cells, created an anti-inflammatory microenvironment in the ischemic brain. Thus, innovative approaches employing EXO-PD-L1-HGF intervention, which targets SDF-1α+ expression, modulates the immune system, and enhances the activation of resident nestin+ NPCs, might significantly alter the brain microenvironment and create a niche conducive to inducing neuroplastic regeneration post-stroke. |
| 巻・号 | 11(36) |
| ページ | e2404882 |
| 公開日 | 2024-9-1 |
| DOI | 10.1002/advs.202404882 |
| PMID | 39049677 |
| PMC | PMC11423231 |
| MeSH | Animals B7-H1 Antigen* / metabolism Disease Models, Animal* Exosomes* / metabolism Forkhead Box Protein O3* / genetics Forkhead Box Protein O3* / metabolism Hepatocyte Growth Factor* / genetics Hepatocyte Growth Factor* / metabolism Male Mesenchymal Stem Cells* / metabolism Mice Mice, Inbred C57BL Neuronal Plasticity* STAT3 Transcription Factor* / metabolism Signal Transduction* Stroke* / metabolism |
| IF | 15.84 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Bluesky |
| 各媒体での言及数の合計 | 2 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 実験動物マウス | RBRC03482 |