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Background <p>Androgenetic alopecia (AGA), the most common form of hair loss, is currently treated with pharmacological agents that often yield inconsistent results and side effects, highlighting the need for novel therapeutic approaches. This study aimed to investigate the therapeutic potential and molecular mechanisms of exosomes derived from dental pulp mesenchymal stem cells (DPSC-Exos) for AGA.</p> Methods <p>We employed a dihydrotestosterone (DHT)-induced AGA mouse model and treated groups with DPSC-Exos or minoxidil. Hair growth was assessed macroscopically and histologically. In vitro, human dermal papilla cells (DPCs) were treated with DHT and/or DPSC-Exos, with or without the PI3K inhibitor LY294002. Analyses included RNA sequencing, RT-qPCR, western blotting, immunofluorescence, and functional assays (proliferation, migration). Statistical significance was determined using Student’s t-test or one-way ANOVA with appropriate post-hoc tests.</p> Results <p>DPSC-Exos significantly promoted hair regrowth, increased hair follicle density, and enhanced dermal thickness in mice, with efficacy comparable to minoxidil. Transcriptomic and protein analysis revealed DPSC-Exos activated the PI3K/Akt pathway and upregulated VEGFA, leading to perifollicular vascular network reconstruction. In vitro, DPSC-Exos rescued DHT-induced suppression of DPC proliferation, migration, and expression of hair-inductive markers (ALP, α-SMA). These effects were mediated through upregulation of pro-angiogenic factors (VEGFA, FGF2, ANGPT1) and were completely abolished by PI3K inhibition, confirming the pathway’s necessity. A positive feedback loop between PI3K/Akt activation and VEGFA expression was identified.</p> Conclusion <p>Our findings demonstrate that DPSC-Exos promote hair regeneration by activating the PI3K/Akt-VEGFA axis, thereby restoring the follicular vascular niche and DPC function. This study positions DPSC-Exos as a promising, cell-free therapeutic strategy for AGA, with clear mechanistic foundations for future translational development.</p>

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Dental pulp stem cell exosomes promote angiogenesis via the PI3K/Akt signaling pathway to treat androgenetic alopecia

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年5月21日

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  • Wangyu Luo,
  • Yue Shen,
  • Wanning Yu,
  • Le Zhao,
  • Miaomiao Wu,
  • Lihua Xu,
  • Ziyan Liu,
  • Liu Yang,
  • Xiaolei Zhang

摘要

Background

Androgenetic alopecia (AGA), the most common form of hair loss, is currently treated with pharmacological agents that often yield inconsistent results and side effects, highlighting the need for novel therapeutic approaches. This study aimed to investigate the therapeutic potential and molecular mechanisms of exosomes derived from dental pulp mesenchymal stem cells (DPSC-Exos) for AGA.

Methods

We employed a dihydrotestosterone (DHT)-induced AGA mouse model and treated groups with DPSC-Exos or minoxidil. Hair growth was assessed macroscopically and histologically. In vitro, human dermal papilla cells (DPCs) were treated with DHT and/or DPSC-Exos, with or without the PI3K inhibitor LY294002. Analyses included RNA sequencing, RT-qPCR, western blotting, immunofluorescence, and functional assays (proliferation, migration). Statistical significance was determined using Student’s t-test or one-way ANOVA with appropriate post-hoc tests.

Results

DPSC-Exos significantly promoted hair regrowth, increased hair follicle density, and enhanced dermal thickness in mice, with efficacy comparable to minoxidil. Transcriptomic and protein analysis revealed DPSC-Exos activated the PI3K/Akt pathway and upregulated VEGFA, leading to perifollicular vascular network reconstruction. In vitro, DPSC-Exos rescued DHT-induced suppression of DPC proliferation, migration, and expression of hair-inductive markers (ALP, α-SMA). These effects were mediated through upregulation of pro-angiogenic factors (VEGFA, FGF2, ANGPT1) and were completely abolished by PI3K inhibition, confirming the pathway’s necessity. A positive feedback loop between PI3K/Akt activation and VEGFA expression was identified.

Conclusion

Our findings demonstrate that DPSC-Exos promote hair regeneration by activating the PI3K/Akt-VEGFA axis, thereby restoring the follicular vascular niche and DPC function. This study positions DPSC-Exos as a promising, cell-free therapeutic strategy for AGA, with clear mechanistic foundations for future translational development.