{
    "abstract": "Mitochondria play a critical role in oxidative stress (OS)-induced neuronal injury during ischemic stroke (IS), making them promising therapeutic targets. Mounting evidence underscores the extraordinary therapeutic promise of exosomes derived from human neural stem cells (hNSCs) in the management of central nervous system (CNS) diseases. Nonetheless, the precise mechanisms by which these exosomes target mitochondria to ameliorate the effects of IS remain only partially elucidated. This study investigates the protective effects of hNSC derived exosomes (hNSC-Exos) on neuronal damage.\nUsing a rat model of middle cerebral artery occlusion (MCAO) in vivo and OS-induced HT22 cells in vitro. Firstly, our research group independently isolated human neural stem cells (hNSCs) and subsequently prepared hNSC-Exos. In vivo, MCAO rats were restored to blood flow perfusion to simulate ischemia-reperfusion injury, and hNSC-Exos were injected through stereotaxic injection into the brain. Subsequently, the protective effects of hNSC-Exos on MCAO rats were evaluated, including histological studies, behavioral assessments. In vivo, H\nAdministration of hNSC-Exos significantly ameliorated brain tissue damage and enhanced behavioral outcomes in MCAO rats. This treatment led to a reduction in brain tissue apoptosis and facilitated the normalization of impaired neurogenesis and neuroplasticity. Notably, the application of hNSC-Exos in vitro resulted in an upregulation of mitophagy in HT22 cells, thereby remedying mitochondrial dysfunction. We demonstrate that hNSC-Exos activate mitophagy via the PINK1/Parkin pathway, improving mitochondrial function and reducing neuronal apoptosis.\nThese findings suggest that hNSC-Exos alleviate OS-induced neuronal damage by regulating the PINK1/Parkin pathway. These reveals a novel role of stem cell-derived mitochondrial therapy in promoting neuroprotection and suggest their potential as a therapeutic approach for OS-associated CNS diseases, including IS.",
    "authors": [
        {
            "affiliation": "Stem Cell Clinical Research Center, The First Affiliated Hospital of Dalian Medical University, No. 193, Lianhe Road, Shahekou District, Dalian, 116011, People's Republic of China.\nNational Local Joint Engineering Laboratory, The First Affiliated Hospital of Dalian Medical University, No. 193, Lianhe Road, Shahekou District, Dalian, 116011, People's Republic of China.\nNational Genetic Test Center, The First Affiliated Hospital of Dalian Medical University, No. 193, Lianhe Road, Shahekou District, Dalian, 116011, People's Republic of China.\nLiaoning Key Laboratory of Frontier Technology of Stem Cell and Precision Medicine, Dalian Innovation Institute of Stem Cell and Precision Medicine, No. 57, Xinda Street, High-Tech Park, Dalian, 116023, People's Republic of China.",
            "firstname": "Mengke",
            "initials": "M",
            "lastname": "Zhao"
        },
        {
            "affiliation": "Stem Cell Clinical Research Center, The First Affiliated Hospital of Dalian Medical University, No. 193, Lianhe Road, Shahekou District, Dalian, 116011, People's Republic of China.\nNational Local Joint Engineering Laboratory, The First Affiliated Hospital of Dalian Medical University, No. 193, Lianhe Road, Shahekou District, Dalian, 116011, People's Republic of China.\nNational Genetic Test Center, The First Affiliated Hospital of Dalian Medical University, No. 193, Lianhe Road, Shahekou District, Dalian, 116011, People's Republic of China.\nLiaoning Key Laboratory of Frontier Technology of Stem Cell and Precision Medicine, Dalian Innovation Institute of Stem Cell and Precision Medicine, No. 57, Xinda Street, High-Tech Park, Dalian, 116023, People's Republic of China.",
            "firstname": "Jiayi",
            "initials": "J",
            "lastname": "Wang"
        },
        {
            "affiliation": "Stem Cell Clinical Research Center, The First Affiliated Hospital of Dalian Medical University, No. 193, Lianhe Road, Shahekou District, Dalian, 116011, People's Republic of China.\nNational Local Joint Engineering Laboratory, The First Affiliated Hospital of Dalian Medical University, No. 193, Lianhe Road, Shahekou District, Dalian, 116011, People's Republic of China.\nNational Genetic Test Center, The First Affiliated Hospital of Dalian Medical University, No. 193, Lianhe Road, Shahekou District, Dalian, 116011, People's Republic of China.\nLiaoning Key Laboratory of Frontier Technology of Stem Cell and Precision Medicine, Dalian Innovation Institute of Stem Cell and Precision Medicine, No. 57, Xinda Street, High-Tech Park, Dalian, 116023, People's Republic of China.",
            "firstname": "Shuaiyu",
            "initials": "S",
            "lastname": "Zhu"
        },
        {
            "affiliation": "Stem Cell Clinical Research Center, The First Affiliated Hospital of Dalian Medical University, No. 193, Lianhe Road, Shahekou District, Dalian, 116011, People's Republic of China.\nNational Local Joint Engineering Laboratory, The First Affiliated Hospital of Dalian Medical University, No. 193, Lianhe Road, Shahekou District, Dalian, 116011, People's Republic of China.\nNational Genetic Test Center, The First Affiliated Hospital of Dalian Medical University, No. 193, Lianhe Road, Shahekou District, Dalian, 116011, People's Republic of China.\nLiaoning Key Laboratory of Frontier Technology of Stem Cell and Precision Medicine, Dalian Innovation Institute of Stem Cell and Precision Medicine, No. 57, Xinda Street, High-Tech Park, Dalian, 116023, People's Republic of China.",
            "firstname": "Shensen",
            "initials": "S",
            "lastname": "Zhang"
        },
        {
            "affiliation": "Stem Cell Clinical Research Center, The First Affiliated Hospital of Dalian Medical University, No. 193, Lianhe Road, Shahekou District, Dalian, 116011, People's Republic of China.\nNational Local Joint Engineering Laboratory, The First Affiliated Hospital of Dalian Medical University, No. 193, Lianhe Road, Shahekou District, Dalian, 116011, People's Republic of China.\nNational Genetic Test Center, The First Affiliated Hospital of Dalian Medical University, No. 193, Lianhe Road, Shahekou District, Dalian, 116011, People's Republic of China.\nLiaoning Key Laboratory of Frontier Technology of Stem Cell and Precision Medicine, Dalian Innovation Institute of Stem Cell and Precision Medicine, No. 57, Xinda Street, High-Tech Park, Dalian, 116023, People's Republic of China.",
            "firstname": "Chao",
            "initials": "C",
            "lastname": "Han"
        },
        {
            "affiliation": "Stem Cell Clinical Research Center, The First Affiliated Hospital of Dalian Medical University, No. 193, Lianhe Road, Shahekou District, Dalian, 116011, People's Republic of China.\nNational Local Joint Engineering Laboratory, The First Affiliated Hospital of Dalian Medical University, No. 193, Lianhe Road, Shahekou District, Dalian, 116011, People's Republic of China.\nNational Genetic Test Center, The First Affiliated Hospital of Dalian Medical University, No. 193, Lianhe Road, Shahekou District, Dalian, 116011, People's Republic of China.\nLiaoning Key Laboratory of Frontier Technology of Stem Cell and Precision Medicine, Dalian Innovation Institute of Stem Cell and Precision Medicine, No. 57, Xinda Street, High-Tech Park, Dalian, 116023, People's Republic of China.",
            "firstname": "Chengcheng",
            "initials": "C",
            "lastname": "Tan"
        },
        {
            "affiliation": "Stem Cell Clinical Research Center, The First Affiliated Hospital of Dalian Medical University, No. 193, Lianhe Road, Shahekou District, Dalian, 116011, People's Republic of China.\nNational Local Joint Engineering Laboratory, The First Affiliated Hospital of Dalian Medical University, No. 193, Lianhe Road, Shahekou District, Dalian, 116011, People's Republic of China.\nNational Genetic Test Center, The First Affiliated Hospital of Dalian Medical University, No. 193, Lianhe Road, Shahekou District, Dalian, 116011, People's Republic of China.\nLiaoning Key Laboratory of Frontier Technology of Stem Cell and Precision Medicine, Dalian Innovation Institute of Stem Cell and Precision Medicine, No. 57, Xinda Street, High-Tech Park, Dalian, 116023, People's Republic of China.",
            "firstname": "Yubing",
            "initials": "Y",
            "lastname": "Huang"
        },
        {
            "affiliation": "Stem Cell Clinical Research Center, The First Affiliated Hospital of Dalian Medical University, No. 193, Lianhe Road, Shahekou District, Dalian, 116011, People's Republic of China.\nNational Local Joint Engineering Laboratory, The First Affiliated Hospital of Dalian Medical University, No. 193, Lianhe Road, Shahekou District, Dalian, 116011, People's Republic of China.\nNational Genetic Test Center, The First Affiliated Hospital of Dalian Medical University, No. 193, Lianhe Road, Shahekou District, Dalian, 116011, People's Republic of China.\nLiaoning Key Laboratory of Frontier Technology of Stem Cell and Precision Medicine, Dalian Innovation Institute of Stem Cell and Precision Medicine, No. 57, Xinda Street, High-Tech Park, Dalian, 116023, People's Republic of China.",
            "firstname": "Zhaokai",
            "initials": "Z",
            "lastname": "Sun"
        },
        {
            "affiliation": "Stem Cell Clinical Research Center, The First Affiliated Hospital of Dalian Medical University, No. 193, Lianhe Road, Shahekou District, Dalian, 116011, People's Republic of China. wangliang@dmu.edu.cn.\nNational Local Joint Engineering Laboratory, The First Affiliated Hospital of Dalian Medical University, No. 193, Lianhe Road, Shahekou District, Dalian, 116011, People's Republic of China. wangliang@dmu.edu.cn.\nNational Genetic Test Center, The First Affiliated Hospital of Dalian Medical University, No. 193, Lianhe Road, Shahekou District, Dalian, 116011, People's Republic of China. wangliang@dmu.edu.cn.\nLiaoning Key Laboratory of Frontier Technology of Stem Cell and Precision Medicine, Dalian Innovation Institute of Stem Cell and Precision Medicine, No. 57, Xinda Street, High-Tech Park, Dalian, 116023, People's Republic of China. wangliang@dmu.edu.cn.",
            "firstname": "Liang",
            "initials": "L",
            "lastname": "Wang"
        },
        {
            "affiliation": "Stem Cell Clinical Research Center, The First Affiliated Hospital of Dalian Medical University, No. 193, Lianhe Road, Shahekou District, Dalian, 116011, People's Republic of China. liujing@dmu.edu.cn.\nNational Local Joint Engineering Laboratory, The First Affiliated Hospital of Dalian Medical University, No. 193, Lianhe Road, Shahekou District, Dalian, 116011, People's Republic of China. liujing@dmu.edu.cn.\nNational Genetic Test Center, The First Affiliated Hospital of Dalian Medical University, No. 193, Lianhe Road, Shahekou District, Dalian, 116011, People's Republic of China. liujing@dmu.edu.cn.\nLiaoning Key Laboratory of Frontier Technology of Stem Cell and Precision Medicine, Dalian Innovation Institute of Stem Cell and Precision Medicine, No. 57, Xinda Street, High-Tech Park, Dalian, 116023, People's Republic of China. liujing@dmu.edu.cn.",
            "firstname": "Jing",
            "initials": "J",
            "lastname": "Liu"
        }
    ],
    "conclusions": null,
    "copyrights": "\u00a9 2025. The Author(s).",
    "doi": "10.1186/s12967-025-06283-y",
    "journal": "Journal of translational medicine",
    "keywords": [
        "Exosomes",
        "Human neural stem cells",
        "Ischemic stroke",
        "Mitophagy",
        "Neuroprotection",
        "Oxidative stress",
        "PINK1/Parkin pathway"
    ],
    "methods": null,
    "publication_date": "2025-04-06",
    "pubmed_id": "40188077\n36323233\n21738161\n32071228\n39390521\n20670828\n25418536\n38526280\n25280822\n15837573\n27554433\n32788451\n35900437\n23442817\n37056148\n25144717\n35761337\n21179058\n33751318\n30501621\n18202199\n23065344\n25230377\n19273585\n39358449\n15349860\n18443288\n25018043\n36989574\n31504668\n34145219\n24842106\n34335233\n36890626\n33344446\n34166712\n29807362\n23253171\n36759901\n39245680\n31877338\n35902882\n11283404\n30637094\n35794095\n38766658\n38059122\n31768005\n32482227\n33950241\n19930058\n29650593\n36567297\n31164072\n37358859\n18216873\n27005615\n36341725\n36761725\n27993726\n17406580\n39248158\n29022898\n35512628\n28848050\n30556744\n37582956\n33111641\n34146484\n35305662\n33391496\n32286918\n32029601\n30602770\n33823204\n37856037\n28923312\n35573832\n39357894\n36123730",
    "results": "Administration of hNSC-Exos significantly ameliorated brain tissue damage and enhanced behavioral outcomes in MCAO rats. This treatment led to a reduction in brain tissue apoptosis and facilitated the normalization of impaired neurogenesis and neuroplasticity. Notably, the application of hNSC-Exos in vitro resulted in an upregulation of mitophagy in HT22 cells, thereby remedying mitochondrial dysfunction. We demonstrate that hNSC-Exos activate mitophagy via the PINK1/Parkin pathway, improving mitochondrial function and reducing neuronal apoptosis.",
    "title": "Human neural stem cell-derived exosomes activate PINK1/Parkin pathway to protect against oxidative stress-induced neuronal injury in ischemic stroke.",
    "xml": "<Element 'PubmedArticle' at 0x788504cc4e50>"
}