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

Abstract

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.

Priming mobilization of hair follicle stem cells triggers permanent loss of regeneration after alkylating chemotherapy

“…The PI3K/Akt pathway, responsible for the mobilization of HFSCs 57 , is a direct participant coregulated tightly with other components of DNA damage repair pathways 36,58 . For tissue regenerative attempts, mouse adult HFSCs exhibit slower activation dynamics only when HFs are severely damaged after ionizing radiation 59 . The priming activation of HFSCs is reminiscent of that observed in ovarian primordial follicles after a single dose of alkylating agent 60 .…”

Functional complexity of hair follicle stem cell niche and therapeutic targeting of niche dysfunction for hair regeneration

“…During catagen, DP is also essential for the recession of the epithelial cylinder through controlled apoptosis/cell death [12]. In addition to physiological cycling, DP might also instruct the anagen repair process to avoid catagen entry when HFs are injured by chemo-and radiotherapy [49,50].…”

PPAR‐γ signalling as a key mediator of human hair follicle physiology and pathology

“…Arguably, interest in the role of PPAR‐γ signalling in HF biology and pathology was initiated and was most pronouncedly fuelled by the work of Karnik and colleagues, who noted, both on the gene expression and metabolite level, a reduction in fatty acid metabolism and peroxisome and cholesterol biogenesis in patients with LPP, the most common primary scarring alopecia . The authors speculated that this reduction may lead to an accumulation of proinflammatory lipids and the subsequent recruitment of inflammatory cells around the bulge, the main seat of HF epithelial stem cells (HFeSCs) . In addition, they reported an immunohistologically assessed downregulation of PPAR‐γ protein expression in lesional scalp skin biopsy from patients with LPP compared to healthy skin …”