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Development of a Model for Chemotherapy-Induced Alopecia: Profiling of Histological Changes in Human Hair Follicles After Chemotherapy.
Journal of Investigative Dermatology 2015 September 16
Optimized research models are required to further understand the pathogenesis and prophylaxis of chemotherapy-induced alopecia (CIA). Our aim was to develop a mouse model for CIA by follicular unit transplantation of human hair follicles onto immunodeficient mice. Twenty-two weeks after transplantation, a single dose of cyclophosphamide (Cph) was administered to mice in the Cph100 (100 mg/kg) and Cph150 (150 mg/kg) groups. On day 6, hair follicles showed dystrophic changes with swollen dermal papilla and ectopic melanin clumping in the hair bulb. In addition, up-regulated expression of apoptotic regulators (P53, Fas/Fas-ligand, TRAIL/TRAIL receptor, and Bax), increased apoptotic matrix keratinocytes, down-regulated Ki67 expression, and decreased melanogenic protein in the hair bulb were noted in both groups. After 12 treatment days, hair follicles in Cph100 mice appeared to diminish dystrophic changes. In contrast, hair follicles of Cph150 mice prematurely entered a dystrophic catagen phase after 9 treatment days, and immunofluorescence staining for Ki67 and melanogenic protein expressions was barely visible. Two hair follicle damage response pathways were observed in this model, namely dystrophic anagen (Cph100) and catagen (Cph150) pathways. Our model might be useful for further understanding the impact of chemotherapy on human hair follicles.Journal of Investigative Dermatology accepted article preview online, 15 September 2015. doi:10.1038/jid.2015.358.
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