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Background <p>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).</p> Methods <p>Primary 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 <i>t</i>-tests were used for data analysis between two groups.</p> Results <p>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-β) concentration was detected in the latter conditioned medium. SCGF-β enhanced RGC survival in vitro and in vivo, and RGC-derived interleukin-12(p70) (IL-12[p70]) promotes secretion of iPSC-derived SCGF-β. Downstream of this IL-12(p70)-to-SCGF-β axis, ngn2 was significantly upregulated, and was found both necessary and sufficient for RGC survival.</p> Conclusion <p>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-β, and SCGF-β protects RGCs via upregulating ngn2, suggesting that neurons may call on stem cells for their own protection.</p>

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Retinal ganglion cells induce stem cell-derived neuroprotection via IL-12 to SCGF-β crosstalk

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年2月25日

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  • Qing Xia,
  • Kun-Che Chang,
  • Yanan Sun,
  • Michael Nahmou,
  • Takahiko Noro,
  • Yun Cheng,
  • Xiangmei Kong,
  • Xiaofen Mo,
  • Jeffrey L. Goldberg,
  • Suqian Wu

摘要

Background

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).

Methods

Primary 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.

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-β) concentration was detected in the latter conditioned medium. SCGF-β enhanced RGC survival in vitro and in vivo, and RGC-derived interleukin-12(p70) (IL-12[p70]) promotes secretion of iPSC-derived SCGF-β. Downstream of this IL-12(p70)-to-SCGF-β axis, ngn2 was significantly upregulated, and was found both necessary and sufficient for RGC survival.

Conclusion

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-β, and SCGF-β protects RGCs via upregulating ngn2, suggesting that neurons may call on stem cells for their own protection.