Harnessing the Secretome of Hair Follicle Fibroblasts to Accelerate Ex Vivo Healing of Human Skin Wounds

Helena Topouzi,Colin J Boyle,Greg Williams,Claire A Higgins

doi:10.1016/j.jid.2019.09.019

Helena Topouzi, Colin J Boyle + Show 2 more

Open Access

https://doi.org/10.1016/j.jid.2019.09.019

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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 invitro and exvivo models of human skin wound closure, we found that hair follicle dermal papilla fibroblasts could accelerate closure of invitro 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 invivo.

Highlights

As the interface of our body with our surroundings, skin provides us with external protection and internal homeostasis
This demonstrates that the dermal papilla fibroblasts (DPFi), papillary fibroblasts (PFi), and reticular fibroblasts (RFi) cultures established from human scalp skin exhibit distinct characteristics from one another, and based on this we concluded that we were growing three different fibroblast subtypes in vitro
DPFi-specific cytokines promote faster wound closure than the control in vitro far, we found that DPFi conditioned medium (CM) could promote significantly faster re-epithelialization of in vitro and ex vivo wounds compared with controls

Summary

Introduction

As the interface of our body with our surroundings, skin provides us with external protection and internal homeostasis. In situations where any one of these processes is perturbed, a chronic or nonhealing wound can arise. It is thought that nonhealing wounds affect 1e2% of the population at any given time, whereas treatment costs account for 2e4% of the healthcare budget in industrialized countries (Guest et al, 2017). Are there grandiose economic effects of chronic wounds, but they can cause severe psychological and physical impact, negatively affecting quality of life of patients (Cole-King and Harding, 2001; Phillips et al, 1994). In the U.S, PDGF-BB has been approved by the Food and Drug Administration for treatment of full-thickness skin

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