title: In vitro characterization of human hair follicle dermal sheath mesenchymal stromal cells and their potential in enhancing diabetic wound healing.
abstract: OBJECTIVE
  Little is published on the characterization and therapeutic potential of human mesenchymal cells derived from hair follicle (HF) dermal sheath (DS). In this study, we isolated and characterized HF DS-mesenchymal stromal cells (DS-MSCs) with respect to the bone marrow mesenchymal stromal cells (BM-MSCs). We further tested if DS-MSC-conditioned medium (CM), like what was previously reported for BM-MSC CM, has superior wound-healing properties, in both in vitro and in vivo wound models compared with skin fibroblast CM.
  
  
  METHODS
  DS-MSCs were isolated from HF and cultured in vitro to assess long-term growth potential, colony-forming efficiency (CFE), expression of CD surface markers and differentiation potential. The cytokine expression of DS-MSC CM was determined through an antibody-based protein array analysis. The wound-healing effects of the CM were tested in vitro with the use of human cell cultures and in vivo with the use of a diabetic mouse wound model.
  
  
  RESULTS
  In vitro results revealed that DS-MSCs have high growth capacity and CFE while displaying some phenotypes similar to BM-MSCs. DS-MSCs strongly expressed many surface markers expressed in BM-MSCs and could also differentiate into osteoblasts, chondrocytes and adipocytes. DS-MSCs secreted significantly higher proportions of paracrine factors such as interleukin-6 (IL-6), IL-8 and growth-related oncogene. DS-MSC-CM demonstrated enhanced wound-healing effects on human skin keratinocytes, fibroblasts and endothelial cells in vitro, and the wound-healing time in diabetic mice was found to be shorter, compared with vehicle controls.
  
  
  CONCLUSIONS
  Human HF DS stromal cells demonstrated MSC-like properties and might be an alternative source for therapeutic use in wound healing.
authors.affiliation: Department of Plastic, Reconstructive and Aesthetic Surgery, Singapore General Hospital, Singapore.
authors.forename: Dongrui
authors.initials: D
authors.lastname: Ma
authors.affiliation: Department of Plastic, Reconstructive and Aesthetic Surgery, Singapore General Hospital, Singapore.
authors.forename: Jonah Ee Hsiang
authors.initials: JE
authors.lastname: Kua
authors.affiliation: Department of Plastic, Reconstructive and Aesthetic Surgery, Singapore General Hospital, Singapore; Skin Bank Unit, Singapore General Hospital, Singapore.
authors.forename: Wee Keng
authors.initials: WK
authors.lastname: Lim
authors.affiliation: Department of Plastic, Reconstructive and Aesthetic Surgery, Singapore General Hospital, Singapore.
authors.forename: Seng Teik
authors.initials: ST
authors.lastname: Lee
authors.affiliation: Department of Plastic, Reconstructive and Aesthetic Surgery, Singapore General Hospital, Singapore; Skin Bank Unit, Singapore General Hospital, Singapore. Electronic address: alvin.chua.w.c@sgh.com.sg.
authors.forename: Alvin Wen Choong
authors.initials: AW
authors.lastname: Chua
mesh_terms: D017667:Adipocytes / Q000166:cytology; D000328:Adult; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects*; D049109:Cell Proliferation; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology; D017077:Culture Media, Conditioned; D003920:Diabetes Mellitus / Q000628:therapy*; D042783:Endothelial Cells / Q000187:drug effects; D005260:Female; D005347:Fibroblasts / Q000187:drug effects; D018859:Hair Follicle / Q000166:cytology*; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D015603:Keratinocytes / Q000187:drug effects; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051379:Mice; D008875:Middle Aged; D010006:Osteoblasts / Q000166:cytology; D012867:Skin / Q000166:cytology*; D017154:Stromal Cells / Q000187:drug effects; D014945:Wound Healing; D055815:Young Adult
chemical_list: D017077:Culture Media, Conditioned; C508600:IL6 protein, human; D015850:Interleukin-6; D016209:Interleukin-8
keywords: dermal sheath; hair follicle; medium; mesenchymal stromal cells; wound healing