Scholarlink

<p>Mesenchymal stem cells (MSCs) show great potential for combating aging-related tissue degeneration, yet their clinical translation is hampered by serum-dependent culture. Here, we report a GMP-compliant serum-free (SF) system for human umbilical cord MSCs (hUC-MSCs) and demonstrate that their secretome exerts superior efficacy against UVB-induced skin photoaging compared to serum-containing counterparts, such as increased dermal thickness, improved angiogenesis and upregulated levels of senescence-associated proteins. Further, this enhanced activity was investigated to correlate with elevated NAMPT. Crucially, FGF2, a predefined SF medium component, was identified as a NAMPT-mediated dual-functional modulator for both delaying MSCs senescence and enhancing the anti-photoaging effect of secretome. Mechanistically, we found that extracellular NAMPT directly counteract photoaging via extracellular vesicle delivery approach, while intracellular NAMPT regulated senescence-, proliferation-, and apoptosis-related genes through FGFR/NAMPT/AMPK signaling pathway, synergistically influencing on the anti-photoaging function of secretome. Our work proposes a cell-free secretome-based strategy for skin anti-photoaging and demonstrates the dual roles of FGF2 in enhancing cell viability and paracrine activity.</p> Graphical Abstract <p>FGF2 up-regulates the iNAMPT expression in MSCs and enhances the eNAMPT delivery to fibroblasts to achieve the anti-photoaging effects of MSCs’ secretome. We discovered that fibroblast growth factor 2 (FGF2) elevated the NAMPT level through the FGFR/AKT pathway in MSCs and enhanced anti-photoaging activity of MSCs’ secretome in two manners. One is that the upregulated intracellular NAMPT (iNAMPT) activates the AMPK pathway to delay cell senescence, suppress apoptosis and accelerate proliferation in MSCs. The other is that the enhanced eNAMPT reaches fibroblast cells from MSCs’ secretome via EVs and increase the NAD<sup>+</sup> level in fibroblast cells. Ultimately, these two ways result in a reduction of p16, p21 and p53 proteins, and cell proliferation in fibroblast cells to resist UVB radiation.</p> <p></p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

FGF2 Enhances MSCs Secretome Therapy for Skin Photoaging by Delaying Senescence via iNAMPT/AMPK Signaling and Facilitating eNAMPT-Mediated Regenerative Crosstalk

  • 期刊论文

  • 发表日期：

    2025年12月2日

查看全文
  • Yixin Zhang,
  • Manping Lu,
  • Jieqing Ouyang,
  • Lin Liang,
  • Fan Li,
  • Zhihan Pei,
  • Lihao Chen,
  • Miaoman Ye,
  • Jiajie Tan,
  • Liwei Xiang,
  • Lijing Kong,
  • Long Huang,
  • Li Fu,
  • Wenhao Wang,
  • Lei Qin,
  • Zhiyong Zhang,
  • Jihui Du

摘要

Mesenchymal stem cells (MSCs) show great potential for combating aging-related tissue degeneration, yet their clinical translation is hampered by serum-dependent culture. Here, we report a GMP-compliant serum-free (SF) system for human umbilical cord MSCs (hUC-MSCs) and demonstrate that their secretome exerts superior efficacy against UVB-induced skin photoaging compared to serum-containing counterparts, such as increased dermal thickness, improved angiogenesis and upregulated levels of senescence-associated proteins. Further, this enhanced activity was investigated to correlate with elevated NAMPT. Crucially, FGF2, a predefined SF medium component, was identified as a NAMPT-mediated dual-functional modulator for both delaying MSCs senescence and enhancing the anti-photoaging effect of secretome. Mechanistically, we found that extracellular NAMPT directly counteract photoaging via extracellular vesicle delivery approach, while intracellular NAMPT regulated senescence-, proliferation-, and apoptosis-related genes through FGFR/NAMPT/AMPK signaling pathway, synergistically influencing on the anti-photoaging function of secretome. Our work proposes a cell-free secretome-based strategy for skin anti-photoaging and demonstrates the dual roles of FGF2 in enhancing cell viability and paracrine activity.

Graphical Abstract

FGF2 up-regulates the iNAMPT expression in MSCs and enhances the eNAMPT delivery to fibroblasts to achieve the anti-photoaging effects of MSCs’ secretome. We discovered that fibroblast growth factor 2 (FGF2) elevated the NAMPT level through the FGFR/AKT pathway in MSCs and enhanced anti-photoaging activity of MSCs’ secretome in two manners. One is that the upregulated intracellular NAMPT (iNAMPT) activates the AMPK pathway to delay cell senescence, suppress apoptosis and accelerate proliferation in MSCs. The other is that the enhanced eNAMPT reaches fibroblast cells from MSCs’ secretome via EVs and increase the NAD+ level in fibroblast cells. Ultimately, these two ways result in a reduction of p16, p21 and p53 proteins, and cell proliferation in fibroblast cells to resist UVB radiation.