Abstract
Hair loss is a common medical problem affecting both males and females. Dermal papilla (DP) cells are the ultimate reservoir of cells with the potential of hair regeneration in hair loss patients. Here, we analyzed the role of macrophage-derived Wnts (3a and 7b) and macrophage extracellular vesicles (MAC-EVs) in promoting hair growth. We studied the proliferation, migration, and expression of growth factors of human-DP cells in the presence or absence of MAC-EVs. Additionally, we tested the effect of MAC-EV treatment on hair growth in a mouse model and human hair follicles. Data from western blot and flow cytometry showed that MAC-EVs were enriched with Wnt3a and Wnt7b, and more than 95% were associated with their membrane. The results suggest that Wnt proteins in MAC-EVs activate the Wnt/β-catenin signaling pathways, which leads to activation of transcription factors (Axin2 and Lef1). The MAC-EVs significantly enhanced the proliferation, migration, and levels of hair-inductive markers of DP cells. Additionally, MAC-EVs phosphorylated AKT and increased the levels of the survival protein Bcl-2. The DP cells treated with MAC-EVs showed increased expression of vascular endothelial growth factor (VEGF) and keratinocyte growth factor (KGF). Treatment of Balb/c mice with MAC-EVs promoted hair follicle (HF) growth in vivo and also increased hair shaft size in a short period in human HFs. Our findings suggest that MAC-EV treatment could be clinically used as a promising novel anagen inducer in the treatment of hair loss.
Highlights
Hair loss is a common disorder resulting from genetic, hormonal, traumatic, and iatrogenic events.It can cause significant psychological stress and adversely affects self-confidence [1,2]
We showed the presence of Wnt3a/Wnt7b proteins in macrophage extracellular vesicles (MAC-Extracellular vesicles (EVs)), which are associated with the membrane
We demonstrated that MAC-EVs promoted proliferation and migration and the activation of the Wnt/β-catenin signaling pathway in Dermal papilla (DP) cells
Summary
Hair loss is a common disorder resulting from genetic, hormonal, traumatic, and iatrogenic events. It can cause significant psychological stress and adversely affects self-confidence [1,2]. Hair follicle (HF) is a self-renewing structure that undergoes a cycle of phases: anagen, catagen, and telogen. The anagen stage is a rapid proliferation of follicular epithelial cells known as matrix cells in the hair bulb, which differentiate to make the hair fiber and follicular root sheath cells. The catagen stage is an apoptosis leading to regression of the lower two thirds of the follicle, preserving the stem cell region, and telogen is a relatively inactive period between the growth phases [2]. Novel strategies with hair growth capability are needed for hair loss treatment
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