Topical Application of Cultured Human Hair Follicle-Derived Epithelial Progenitor Cells Enhances Wound Healing and Epithelialization

Background: Epithelial cell-based approaches - including cultured keratinocyte sheets, bilayered skin substitutes, and cell-enriched wound dressings derived from epidermal cells - have been explored to enhance wound epithelialization; however, most studies have focused on epidermis-derived cells. Wound-healing potential of epithelial cells originating from different regions of human hair follicle remains insufficiently characterized. Methods: Epithelial cells were isolated from distinct regions of human scalp hair follicles, including upper root epithelial cells (UECs), lower root epithelial cells (LECs), and bulb epithelial cells (BECs), and were compared with epidermal keratinocytes. Cell viability, proliferation, and phenotypic characteristics were evaluated in vitro . In vivo epithelialization was assessed using a full-thickness wound model in immunodeficient mice following topical application of each cell population. Histological analyses were performed on healed tissue, and donor-site outcomes were explored using a rat whisker model. Results: BECs exhibited the highest viability and proliferative capacity, along with a lower proportion of differentiated keratinocytes. All cell-treated groups enhanced epithelialization compared to controls, with BECs-treated wounds showing the most pronounced improvement. Histological analysis demonstrated reduced scar formation and increased retention of human-derived cells in regenerated epidermis following BECs treatment. In rat model, hair follicle regeneration was observed after bulb removal, although regenerated whiskers exhibited reduced thickness and length. Conclusion: These findings provide proof-of-concept evidence that epithelial cells derived from the human hair follicle bulb possess favorable biological properties and enhance epithelialization in preclinical wound model. Hair follicle–derived epithelial cells may represent promising cell source for cutaneous regeneration, although further investigation is required to establish clinical applicability.