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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.

Author information

Rajendran RL1,2, Gangadaran P1,2,3, Seo CH4, Kwack MH5, Oh JM1,2,3, Lee HW1,2, Gopal A1,2, Sung YK3,5, Jeong SY1,2, Lee SW1,2, Lee J1,2, Ahn BC1,2,3.
1
Department of Nuclear Medicine, School of Medicine, Kyungpook National University, Daegu-41944, Korea.
2
Department of Nuclear Medicine, Kyungpook National University Hospital, Daegu-41944, Korea.
3
BK21 Plus KNU Biomedical Convergence Program, Department of Biomedical Science, School of Medicine, Kyungpook National University, Daegu-41944, Korea.
4
New Drug Development Center, Daegu-Gyeongbuk Medical Innovation Foundation (DGMIF), Daegu-41061, Korea.
5
Department of Immunology, School of Medicine, Kyungpook National University, Daegu-41944, Korea.