Potential of Hair Follicle Stem Cell-Derived Exosomes Carrying miR-181a-5p to Promote the Telogen-to-Anagen Stage

Hair loss is a common clinical and aesthetic concern, and existing treatments remain limited by side effects, invasiveness, or unsatisfactory long-term efficacy. Stem cell-derived exosomes have emerged as a promising cell-free strategy for tissue regeneration. However, the hair-regenerative potential of hair follicle stem cell-derived exosomes (HFSC-Exos), particularly when enriched with miR-181a-5p, remains insufficiently explored.

Commercially available rat hair follicle stem cells (HFSCs) were cultured, and exosomes were isolated from cells at passages 3-4 after transfection with miR-181a-5p mimics or negative control mimics. Exosomes were characterized by transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and western blotting. Twenty 7-week-old C57BL/6 mice, which were generally in telogen at this age, were randomly assigned to four groups (n = 5/group): PBS, Exos, Exos^miR-NC, and Exos^miR-181a-5p. After dorsal hair shaving, mice received local subcutaneous injections every other day for a total of five injections. Hair regrowth was evaluated by gross observation, histology, immunohistochemistry, and immunofluorescence.

HFSC-Exos accelerated the transition from telogen to anagen and promoted visible hair regrowth compared with PBS treatment. Among all groups, Exos^miR-181a-5p showed the strongest effect, with newborn hair coverage reaching approximately 90% on day 15, compared with approximately 40% in the Exos and Exos^miR-NC groups. In addition, Ki-67, Bcl-2, and β-catenin expression levels were significantly increased, whereas Bax expression was decreased in exosome-treated skin tissues (all P < 0.05), with the most pronounced changes observed in the Exos^miR-181a-5p group.

HFSC-Exos promoted the telogen-to-anagen transition and hair regrowth in vivo. Enrichment of miR-181a-5p enhanced this effect and was associated with activation of the Wnt/β-catenin pathway, although direct target validation remains to be established.

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