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<p>In the pathogenesis of spinal cord injury (SCI), excessive and persistent neuroinflammation plays a crucial role in the development of the condition. Despite significant advances in modern medicine, there remains a lack of definitive treatments that can fully restore neurological function in patients with SCI. Research has demonstrated that A2-reactive astrocytes are beneficial for the recovery of neurological function following SCI. Therefore, we utilized Transwell co-culture of peripheral blood-derived mesenchymal stem cells (PB-MSCs) with astrocytes (AS) to explore the potential mechanism by which PB-MSCs polarize AS to the A2 phenotype through the TGF-β/PI3K/Akt signaling pathway. In this study, ELISA analysis revealed that PB-MSCs and their conditioned medium (P-CM) significantly induced the expression of IL-10, IL-13, and TGF-β in AS.&#xa0;The addition of LY294002 and AF-101 reversed this effect. Furthermore, western blotting and immunofluorescence assays demonstrated that p-Akt signaling was significantly upregulated in AS co-cultured with PB-MSCs or P-CM, accompanied by an increase in the A2-reactive phenotype marker S100A10. This effect could also be reversed by inhibiting the PI3K/Akt pathway with LY294002 and AF-101. In conclusion, PB-MSCs can mediate the polarization of AS toward the A2 phenotype by activating the PI3K/Akt pathway.</p> Graphical Abstract <p></p>

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Peripheral Blood-Derived Mesenchymal Stem Cells Promote A2 Phenotype Polarization in Astrocytes via TGF-β-Mediated PI3K/Akt Pathway Activation

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年7月2日

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  • Rui-Lin Yang,
  • De-Zhi Zhao,
  • Han-Xiao Wei,
  • Si-Yu Chen,
  • Yi-Bing Yang,
  • Kang Yang,
  • Wen Yan,
  • Tao Zhang

摘要

In the pathogenesis of spinal cord injury (SCI), excessive and persistent neuroinflammation plays a crucial role in the development of the condition. Despite significant advances in modern medicine, there remains a lack of definitive treatments that can fully restore neurological function in patients with SCI. Research has demonstrated that A2-reactive astrocytes are beneficial for the recovery of neurological function following SCI. Therefore, we utilized Transwell co-culture of peripheral blood-derived mesenchymal stem cells (PB-MSCs) with astrocytes (AS) to explore the potential mechanism by which PB-MSCs polarize AS to the A2 phenotype through the TGF-β/PI3K/Akt signaling pathway. In this study, ELISA analysis revealed that PB-MSCs and their conditioned medium (P-CM) significantly induced the expression of IL-10, IL-13, and TGF-β in AS. The addition of LY294002 and AF-101 reversed this effect. Furthermore, western blotting and immunofluorescence assays demonstrated that p-Akt signaling was significantly upregulated in AS co-cultured with PB-MSCs or P-CM, accompanied by an increase in the A2-reactive phenotype marker S100A10. This effect could also be reversed by inhibiting the PI3K/Akt pathway with LY294002 and AF-101. In conclusion, PB-MSCs can mediate the polarization of AS toward the A2 phenotype by activating the PI3K/Akt pathway.

Graphical Abstract