{
    "abstract": "Stem cell-derived secreted factors could protect neurons in neurodegenerative disease or after injury. The exact neuroprotective components in the secretome remain challenging to discover. Here we developed a cell-to-cell interaction model to identify a retinal ganglion cell (RGC)-protective factor derived from induced pluripotent stem cells (iPSCs).\nPrimary RGCs were co-cultured with iPSCs or treated with iPSC-conditioned media in vitro. Cell viability were assayed using live-cell staining, and culture supernatant were analyzed via multiplexed antibody-based assays and ELISA. In vivo tests were carried out under mouse optic nerve crush model and RGC transplantation study in rats. Paired t-tests were used for data analysis between two groups.\nRGC viability was significantly enhanced when iPSCs were first stimulated with RGC-derived supernatant before iPSC-conditioned medium was collected and added into RGC culture. A significant increase of stem cell growth factor-beta (SCGF-\u03b2) concentration was detected in the latter conditioned medium. SCGF-\u03b2 enhanced RGC survival in vitro and in vivo, and RGC-derived interleukin-12(p70) (IL-12[p70]) promotes secretion of iPSC-derived SCGF-\u03b2. Downstream of this IL-12(p70)-to-SCGF-\u03b2 axis, ngn2 was significantly upregulated, and was found both necessary and sufficient for RGC survival.\nThis study addresses a longstanding question of how neurons and stem cells interact to promote neuroprotection, and define a novel molecular interaction pathway whereby RGC's secretion of IL-12(p70) enhances iPSCs' secretion of SCGF-\u03b2, and SCGF-\u03b2 protects RGCs via upregulating ngn2, suggesting that neurons may call on stem cells for their own protection.",
    "authors": [
        {
            "affiliation": "Shanghai Key Laboratory of Visual Impairment and Restoration, Department of Ophthalmology and Vision Science, Eye & ENT Hospital, Fudan University, Shanghai, 200031, China.",
            "firstname": "Qing",
            "initials": "Q",
            "lastname": "Xia"
        },
        {
            "affiliation": "Spencer Center for Vision Research, Byers Eye Institute, Stanford University School of Medicine, Palo Alto, CA, 94304, USA.\nDepartment of Ophthalmology and Neurobiology, School of Medicine, University of Pittsburgh, Pittsburgh, PA, 15213, USA.",
            "firstname": "Kun-Che",
            "initials": "KC",
            "lastname": "Chang"
        },
        {
            "affiliation": "Shanghai Key Laboratory of Visual Impairment and Restoration, Department of Ophthalmology and Vision Science, Eye & ENT Hospital, Fudan University, Shanghai, 200031, China.",
            "firstname": "Yanan",
            "initials": "Y",
            "lastname": "Sun"
        },
        {
            "affiliation": "Spencer Center for Vision Research, Byers Eye Institute, Stanford University School of Medicine, Palo Alto, CA, 94304, USA.",
            "firstname": "Michael",
            "initials": "M",
            "lastname": "Nahmou"
        },
        {
            "affiliation": "Spencer Center for Vision Research, Byers Eye Institute, Stanford University School of Medicine, Palo Alto, CA, 94304, USA.\nDepartment of Ophthalmology, Jikei University School of Medicine, Tokyo, 105-8461, Japan.",
            "firstname": "Takahiko",
            "initials": "T",
            "lastname": "Noro"
        },
        {
            "affiliation": "Shanghai Key Laboratory of Visual Impairment and Restoration, Department of Ophthalmology and Vision Science, Eye & ENT Hospital, Fudan University, Shanghai, 200031, China.",
            "firstname": "Yun",
            "initials": "Y",
            "lastname": "Cheng"
        },
        {
            "affiliation": "Shanghai Key Laboratory of Visual Impairment and Restoration, Department of Ophthalmology and Vision Science, Eye & ENT Hospital, Fudan University, Shanghai, 200031, China.",
            "firstname": "Xiangmei",
            "initials": "X",
            "lastname": "Kong"
        },
        {
            "affiliation": "Shanghai Key Laboratory of Visual Impairment and Restoration, Department of Ophthalmology and Vision Science, Eye & ENT Hospital, Fudan University, Shanghai, 200031, China. xfmo@fudan.edu.cn.",
            "firstname": "Xiaofen",
            "initials": "X",
            "lastname": "Mo"
        },
        {
            "affiliation": "Spencer Center for Vision Research, Byers Eye Institute, Stanford University School of Medicine, Palo Alto, CA, 94304, USA. jlgoldbe@stanford.edu.",
            "firstname": "Jeffrey L",
            "initials": "JL",
            "lastname": "Goldberg"
        },
        {
            "affiliation": "Shanghai Key Laboratory of Visual Impairment and Restoration, Department of Ophthalmology and Vision Science, Eye & ENT Hospital, Fudan University, Shanghai, 200031, China. sqwu15@fudan.edu.cn.\nSpencer Center for Vision Research, Byers Eye Institute, Stanford University School of Medicine, Palo Alto, CA, 94304, USA. sqwu15@fudan.edu.cn.",
            "firstname": "Suqian",
            "initials": "S",
            "lastname": "Wu"
        }
    ],
    "conclusions": "This study addresses a longstanding question of how neurons and stem cells interact to promote neuroprotection, and define a novel molecular interaction pathway whereby RGC's secretion of IL-12(p70) enhances iPSCs' secretion of SCGF-\u03b2, and SCGF-\u03b2 protects RGCs via upregulating ngn2, suggesting that neurons may call on stem cells for their own protection.",
    "copyrights": "\u00a9 2025. The Author(s).",
    "doi": "10.1186/s13287-025-04198-5",
    "journal": "Stem cell research & therapy",
    "keywords": [],
    "methods": null,
    "publication_date": "2025-02-26",
    "pubmed_id": "40001251\n35876610\n33342406\n32622558\n25451858\n26903387\n30923338\n36808392\n26497794\n24176979\n29625481\n33377046\n30626963\n7576630\n2908449\n23818667\n26843334\n33441400\n35269441\n35052785\n33826976\n9705843\n32003015\n7688022\n10652440\n36009430\n35017157\n16505037\n36368332\n29770538\n23856066\n20144606\n30483060\n33674582\n25998495\n34367477",
    "results": "RGC viability was significantly enhanced when iPSCs were first stimulated with RGC-derived supernatant before iPSC-conditioned medium was collected and added into RGC culture. A significant increase of stem cell growth factor-beta (SCGF-\u03b2) concentration was detected in the latter conditioned medium. SCGF-\u03b2 enhanced RGC survival in vitro and in vivo, and RGC-derived interleukin-12(p70) (IL-12[p70]) promotes secretion of iPSC-derived SCGF-\u03b2. Downstream of this IL-12(p70)-to-SCGF-\u03b2 axis, ngn2 was significantly upregulated, and was found both necessary and sufficient for RGC survival.",
    "title": "Retinal ganglion cells induce stem cell-derived neuroprotection via IL-12 to SCGF-\u03b2 crosstalk.",
    "xml": "<Element 'PubmedArticle' at 0x7885047f3b50>"
}