title: Development of a Model for Chemotherapy-Induced Alopecia: Profiling of Histological Changes in Human Hair Follicles after Chemotherapy.
abstract: Optimized research models are required to further understand the pathogenesis and prophylaxis of chemotherapy-induced alopecia. Our aim was to develop a mouse model for chemotherapy-induced alopecia 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, upregulated expression of apoptotic regulators [P53, Fas/Fas-ligand, tumor necrosis factor-related apoptosis-inducing ligand/tumor necrosis factor-related apoptosis-inducing ligand receptor (TRAIL/TRAIL receptor), and Bax], increased apoptotic matrix keratinocytes, downregulated 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.
authors.affiliation: Laboratory of Cutaneous Aging and Hair Research, Biomedical Research Institute, Seoul National University Hospital, Seoul, Korea; Institute of Human-Environment Interface Biology, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Ji-Seon
authors.initials: JS
authors.lastname: Yoon
authors.affiliation: Laboratory of Cutaneous Aging and Hair Research, Biomedical Research Institute, Seoul National University Hospital, Seoul, Korea; Institute of Human-Environment Interface Biology, Seoul National University College of Medicine, Seoul, Korea; Department of Dermatology, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Mira
authors.initials: M
authors.lastname: Choi
authors.affiliation: Laboratory of Cutaneous Aging and Hair Research, Biomedical Research Institute, Seoul National University Hospital, Seoul, Korea; Institute of Human-Environment Interface Biology, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Chang Yup
authors.initials: CY
authors.lastname: Shin
authors.affiliation: Laboratory of Cutaneous Aging and Hair Research, Biomedical Research Institute, Seoul National University Hospital, Seoul, Korea; Institute of Human-Environment Interface Biology, Seoul National University College of Medicine, Seoul, Korea; Department of Dermatology, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Seung Hwan
authors.initials: SH
authors.lastname: Paik
authors.affiliation: Laboratory of Cutaneous Aging and Hair Research, Biomedical Research Institute, Seoul National University Hospital, Seoul, Korea; Institute of Human-Environment Interface Biology, Seoul National University College of Medicine, Seoul, Korea; Department of Dermatology, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Kyu Han
authors.initials: KH
authors.lastname: Kim
authors.affiliation: Laboratory of Cutaneous Aging and Hair Research, Biomedical Research Institute, Seoul National University Hospital, Seoul, Korea; Institute of Human-Environment Interface Biology, Seoul National University College of Medicine, Seoul, Korea; Department of Dermatology, Seoul National University College of Medicine, Seoul, Korea. Electronic address: oskwon@snu.ac.kr.
authors.forename: Ohsang
authors.initials: O
authors.lastname: Kwon
mesh_terms: D000505:Alopecia / Q000139:chemically induced* / Q000473:pathology*; D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000009:adverse effects / Q000494:pharmacology; D001707:Biopsy, Needle; D003520:Cyclophosphamide / Q000009:adverse effects* / Q000494:pharmacology; D004195:Disease Models, Animal; D018859:Hair Follicle / Q000187:drug effects* / Q000254:growth & development / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D016513:Mice, SCID; D011897:Random Allocation; D012016:Reference Values
chemical_list: D018906:Antineoplastic Agents, Alkylating; D003520:Cyclophosphamide