State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, School of Life Science and Technology, China Pharmaceutical University, Nanjing, 210009, China.
Nanjing Ailote Cell Technology Research Institute Co., Ltd, Nanjing, 211103, China.
Stem Cell Res Ther. 2024 Nov 19;15(1):439. doi: 10.1186/s13287-024-04051-1.
BACKGROUND: The use of mesenchymal stem cells (MSCs) is recognized as a promising strategy for the treatment of androgenetic alopecia (AGA). However, the underlying mechanism remains to be explored. Here, we evaluated the therapeutic effects and potential mechanisms of the use of human umbilical cord mesenchymal stem cells (hUCMSCs) in dihydrotestosterone (DHT)-induced AGA models in vivo and in vitro. METHODS: Intradermal transplantation of hUCMSCs was performed in AGA model mice and therapeutic effects were evaluated using histological and immunofluorescence staining. Transwell assays were used for co-culture of hUCMSCs and dermal papilla cells (DPCs), and communication was assessed using RT-qPCR, immunofluorescence, and apoptosis analysis. Interactions between DPCs and hair follicle stem cells (HFSCs) were investigated using RT-qPCR, EdU assays, and cell cycle analysis. RESULTS: Treatment of AGA mice with hUCMSCs promoted hair growth, HFs density, skin thickness, and anagen phase activation, while inhibiting DPCs apoptosis, and promoting HFSCs proliferation. In vitro, hUCMSCs activated Wnt/β-catenin signaling in DPCs via Wntless (Wls), while stimulating growth factor secretion and HFSCs proliferation. Blocking β-catenin degradation with MSAB increased DPCs apoptosis, reduced growth factor secretion, and retarded HFSCs proliferation. CONCLUSION: hUCMSCs promoted hair regeneration in AGA model mice. This was found to be dependent on reducing DPCs apoptosis, thereby relieving the inhibitory effects of DPCs on the growth of HFSCs. The activation of the Wnt/β-catenin signaling pathway was shown to play a crucial role in the promotion of hair growth by hUCMSCs in AGA mice.
背景：间充质干细胞（MSCs）的应用被认为是治疗雄激素性脱发（AGA）的有前途的策略。然而，其潜在机制仍有待探索。在这里，我们评估了人脐带间充质干细胞（hUCMSCs）在体内和体外二氢睾酮（DHT）诱导的 AGA 模型中的治疗效果和潜在机制。
方法：在 AGA 模型小鼠中进行 hUCMSC 皮内移植，并通过组织学和免疫荧光染色评估治疗效果。使用 Transwell 测定进行 hUCMSC 和真皮乳头细胞（DPC）的共培养，并通过 RT-qPCR、免疫荧光和凋亡分析评估通讯。使用 RT-qPCR、EdU 测定和细胞周期分析研究 DPC 和毛囊干细胞（HFSCs）之间的相互作用。
结果：用 hUCMSC 治疗 AGA 小鼠可促进毛发生长、HFs 密度、皮肤厚度和生长期激活，同时抑制 DPC 细胞凋亡，促进 HFSCs 增殖。在体外，hUCMSC 通过 Wntless（Wls）激活 DPC 中的 Wnt/β-catenin 信号通路，同时刺激生长因子分泌和 HFSCs 增殖。用 MSAB 阻断 β-catenin 降解会增加 DPC 细胞凋亡，减少生长因子分泌，并延迟 HFSCs 增殖。
结论：hUCMSC 促进 AGA 模型小鼠的毛发生长。这被发现依赖于减少 DPC 细胞凋亡，从而减轻 DPC 对 HFSCs 生长的抑制作用。Wnt/β-catenin 信号通路的激活在 hUCMSC 促进 AGA 小鼠毛发生长中起着关键作用。
J Cosmet Dermatol. 2024-3
Eur J Med Chem. 2024-1-15
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