Harnessing the secretome of hair follicle fibroblasts to accelerate ex vivo healing of human skin wounds
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Published version
Author(s)
Topouzi, Helena
Boyle, Colin
Williams, Greg
Higgins, Claire
Type
Journal Article
Abstract
In skin homeostasis, dermal fibroblasts are responsible for coordinating the migration and differentiation of overlying epithelial keratinocytes. As hairy skin heals faster than nonhairy skin, we took bio-inspiration from the follicle and hypothesized that follicular fibroblasts would accelerate skin re-epithelialization after injury faster than interfollicular fibroblasts. Using both in vitro and ex vivo models of human skin wound closure, we found that hair follicle dermal papilla fibroblasts could accelerate closure of in vitro scratch wounds by 1.8-fold and epithelial growth capacity by 1.5-fold compared with controls (P < 0.05). We used a cytokine array to determine how the dermal papilla fibroblasts were eliciting this effect and identified two cytokines, sAXL and CCL19, that are released at significantly higher levels by follicular fibroblasts than by interfollicular subtypes. Using sAXL and CCL19 individually, we found that they could also increase closure of epithelial cells in a scratch wound by 1.2- and 1.5-fold, respectively, compared with controls (P < 0.05). We performed an unbiased transcriptional analysis, combined with pathway analysis, and postulate that sAXL accelerates wound closure by promoting migration and inhibiting epithelial differentiation of skin keratinocytes. Long term, we believe these results can be exploited to accelerate wound closure of human skin in vivo.
Date Issued
2020-05-01
Date Acceptance
2019-09-27
Citation
Journal of Investigative Dermatology, 2020, 140 (5), pp.1075-1084.e11
ISSN
0022-202X
Publisher
Elsevier
Start Page
1075
End Page
1084.e11
Journal / Book Title
Journal of Investigative Dermatology
Volume
140
Issue
5
Copyright Statement
© 2019 The Authors. Published by Elsevier, Inc. on behalf of the Society for Investigative Dermatology. This is an open accessarticle under the CC BY license (http://creativecommons.org/licenses/by/4.0/)
Sponsor
Engineering & Physical Science Research Council (EPSRC)
Rosetrees Trust
Imperial MRC Confidence in Concept
Identifier
https://www.jidonline.org/article/S0022-202X(19)33375-5/fulltext
Grant Number
EP/N026845/1
M734
Subjects
Science & Technology
Life Sciences & Biomedicine
Dermatology
DONOR SITE
STEM-CELLS
PAPILLARY
ACTIN
SCALP
HETEROGENEITY
EXPRESSION
CONTRIBUTE
PATTERNS
GRAFTS
Adult
Bodily Secretions
Cell Differentiation
Cell Movement
Cell Proliferation
Cells, Cultured
Chemokine CCL19
Epithelial Cells
Fibroblasts
Hair Follicle
Humans
Keratinocytes
Male
Middle Aged
Organ Culture Techniques
Proteome
Proto-Oncogene Proteins
Receptor Protein-Tyrosine Kinases
Skin
Wound Healing
Wounds and Injuries
Hair Follicle
Cells, Cultured
Fibroblasts
Epithelial Cells
Keratinocytes
Bodily Secretions
Skin
Humans
Wounds and Injuries
Receptor Protein-Tyrosine Kinases
Proto-Oncogene Proteins
Proteome
Organ Culture Techniques
Wound Healing
Cell Differentiation
Cell Proliferation
Cell Movement
Adult
Middle Aged
Male
Chemokine CCL19
Dermatology & Venereal Diseases
1103 Clinical Sciences
1112 Oncology and Carcinogenesis
Publication Status
Published
Date Publish Online
2019-12-16