Restoration of follicular β-catenin signaling by mesenchymal stem cells promotes hair growth in mice with androgenetic alopecia

作者：Wenjing Yan, Jiakun Liu, Jiakun Liu, Xuedong Xie, Qianqian Jin, Yue Yang, Yi Pan, Fangfang Zhang, Fangfang Zhang, Yan Wang, 良樹 鷹津, Jianxing Liu, 良樹 鷹津 · 发表于：Stem Cell Research & Therapy · 年份：2024 · DOI：10.1186/s13287-024-04051-1 · 被引用次数：22 · 研究领域：Hair Growth and Disorders、Mesenchymal stem cell research、Wnt/β-catenin signaling in development and cancer

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 ...