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Anagen hair follicle repair: Timely regenerative attempts from plastic extra‐bulge epithelial cells

Anagen hair follicle repair (AHFR) is the regenerative scheme activated to restore the structure and hair growth following injuries to anagen hair follicles. Compared with telogen‐to‐anagen regeneration and hair follicle neogenesis, AHFR is a clinically important, yet relatively unexplored regenerative feature of hair follicles. Due to their highly proliferative character, germinative cells and matrix cells within hair bulbs are highly susceptible to injuries, such as chemotherapy and radiotherapy. Clinical and experimental observations suggest that damaged anagen hair follicles are able to repair themselves to resume anagen growth, bypassing premature catagen/telogen entry. Mechanistically, extra‐bulge epithelial cells in the outer root sheath and the lower proximal cup are quickly mobilized for regeneration. These cells acquire stem cell‐like properties, exhibiting high plasticity by breaking lineage restriction to regenerate all cell types in the lower segment of anagen hair follicles. Facilitating extra‐bulge epithelial cells’ mobilization ameliorates hair loss from chemo‐ and radiotherapy. On the other hand, quiescent bulge stem cells can also be activated, but only after more severe injuries and with slower activation dynamics. They show limited plasticity and regenerate part of the outer root sheath only. The dysrhythmic activation might render bulge stem cells susceptible to concomitant injuries due to their exit from quiescence.