Masahiro Kiso1, Tatsuo S Hamazaki2, Munenari Itoh1, Sota Kikuchi1, Hidemi Nakagawa1, Hitoshi Okochi3. 1. Department of Dermatology, The Jikei University School of Medicine, Japan. 2. Department of Regenerative Medicine, Research Institute, National Center for Global Health and Medicine, Japan. 3. Department of Regenerative Medicine, Research Institute, National Center for Global Health and Medicine, Japan. Electronic address: hokochi@ri.ncgm.go.jp.
Abstract
BACKGROUND: The dermal papilla is composed of a small clump of mesenchymal cells, called dermal papilla cells (DPCs). DPCs closely interact with epidermal cells to give rise to hair follicles and shafts during hair follicle development and the hair cycle. DPCs are promising cell sources for hair regeneration therapy for alopecia patients. However, once DPCs are put into conventional two-dimensional culture conditions, they quickly lose their capability to produce hair follicles. OBJECTIVE: We aimed to expand a sufficiently large population of DPCs that retain their hair inductive activity. METHODS: Murine DPCs were cultured in the presence of platelet-derived growth factor-AA (PDGF-AA) and fibroblast growth factor 2 (FGF2). Expressions of follicular-related genes were analyzed by real time PCR and hair inductive activity was determined by patch assay and chamber assay in vivo. RESULTS: FGF2 significantly increased the expression of platelet-derived growth factor receptor alpha (PDGFRα) in cultured vibrissal DPCs. PDGF-AA, a ligand of PDGFRα, promoted proliferation of DPCs synergistically when utilized with FGF2 and enhanced the expression of several follicular-related genes in DPCs. Hair reconstitution assays revealed that DPCs treated with both PDGF-AA and FGF-2 were able to maintain their hair inductive activity better than those treated with FGF2 alone. CONCLUSION: Both cell proliferation and hair inductive activity in murine DPCs are maintained by the synergistic effect of FGF2 and PDGF-AA.
BACKGROUND: The dermal papilla is composed of a small clump of mesenchymal cells, called dermal papilla cells (DPCs). DPCs closely interact with epidermal cells to give rise to hair follicles and shafts during hair follicle development and the hair cycle. DPCs are promising cell sources for hair regeneration therapy for alopeciapatients. However, once DPCs are put into conventional two-dimensional culture conditions, they quickly lose their capability to produce hair follicles. OBJECTIVE: We aimed to expand a sufficiently large population of DPCs that retain their hair inductive activity. METHODS:MurineDPCs were cultured in the presence of platelet-derived growth factor-AA (PDGF-AA) and fibroblast growth factor 2 (FGF2). Expressions of follicular-related genes were analyzed by real time PCR and hair inductive activity was determined by patch assay and chamber assay in vivo. RESULTS:FGF2 significantly increased the expression of platelet-derived growth factor receptor alpha (PDGFRα) in cultured vibrissal DPCs. PDGF-AA, a ligand of PDGFRα, promoted proliferation of DPCs synergistically when utilized with FGF2 and enhanced the expression of several follicular-related genes in DPCs. Hair reconstitution assays revealed that DPCs treated with both PDGF-AA and FGF-2 were able to maintain their hair inductive activity better than those treated with FGF2 alone. CONCLUSION: Both cell proliferation and hair inductive activity in murineDPCs are maintained by the synergistic effect of FGF2 and PDGF-AA.
Authors: Pietro Gentile; John P Cole; Megan A Cole; Simone Garcovich; Alessandra Bielli; Maria Giovanna Scioli; Augusto Orlandi; Chiara Insalaco; Valerio Cervelli Journal: Int J Mol Sci Date: 2017-02-14 Impact factor: 5.923