Dermal papilla cells and melanocytes response to physiological oxygen levels depends on their interactions.

Carla M Abreu,Alexandra P Marques,Rui L Reis

doi:10.1111/cpr.13013

Abstract

BackgroundHuman dermal papilla (DP) cells and melanocytes (hMel) are central players in hair growth and pigmentation, respectively. In hair follicles (HFs), oxygen (O2) levels average 5%, being coupled with the production of reactive oxygen species (ROS), necessary to promote hair growth.Materials and MethodsDP cell and hMel proliferation and phenotype were studied under physiological (5%O2, physoxia) or atmospheric (21%O2, normoxia) oxygen levels. hMel‐DP cells interactions were studied in indirect co‐culture or by directly co‐culturing hMel with DP spheroids, to test whether their interaction affected the response to physoxia.ResultsPhysoxia decreased DP cell senescence and improved their secretome and phenotype, as well as hMel proliferation, migration, and tyrosinase activity. In indirect co‐cultures, physoxia affected DP cells’ alkaline phosphatase (ALP) activity but their signalling did not influence hMel proliferation or tyrosinase activity. Additionally, ROS production was higher than in monocultures but a direct correlation between ROS generation and ALP activity in DP cells was not observed. In the 3D aggregates, where hMel are organized around the DP, both hMel tyrosinase and DP cells ALP activities, their main functional indicators, plus ROS production were higher in physoxia than normoxia.ConclusionsOverall, we showed that the response to physoxia differs according to hMel‐DP cells interactions and that the microenvironment recreated when in direct contact favours their functions, which can be relevant for hair regeneration purposes.

Highlights

IntroductionOxygen (O2) is a basic component of the tissue's microenvironment, and their fluctuation can deeply affect cellular metabolism, signalling, proliferation, differentiation and reactive oxygen species (ROS) formation.[12,13] Physiological ROS play a regulatory role in several cellular signalling events.14-16 For example, melanogenesis itself is a ROS generator cellular process, but melanocytes have mechanisms to cope with oxidative stress and avoid cellular damage
Hair growth is mainly controlled by the dermal papilla (DP), the hair follicle (HF) inductive mesenchymal structure, whereas its pigmentation relies on the melanogenic activity of follicular melanocytes.[1,2]
These melanocytes represent the progeny of melanoblasts residing in the bulge, which proliferate and migrate to the hair bulb, surrounding the DP and starting to produce and transfer melanin to the keratinocytes of the growing shaft.3-7 the DP is considered the HF control centre, and its anatomical proximity with bulbar melanocytes implies a role in hair pigmentation, little is known about the capacity of DP cells

Summary

Introduction

Oxygen (O2) is a basic component of the tissue's microenvironment, and their fluctuation can deeply affect cellular metabolism, signalling, proliferation, differentiation and reactive oxygen species (ROS) formation.[12,13] Physiological ROS play a regulatory role in several cellular signalling events.14-16 For example, melanogenesis itself is a ROS generator cellular process, but melanocytes have mechanisms to cope with oxidative stress and avoid cellular damage These include, among others, upregulation of the antioxidant response,[17,18] and expression of the nuclear erythroid 2-related factor (NRF2)[19,20] or the Ataxia Telangiectasia Mutated (ATM) protein.[21] In opposition, uncontrolled levels of ROS have been linked to the aetiopathogenesis of several conditions, including androgenetic alopecia and hair greying.[22,23] It is well known that ROS accumulate at supraphysiological oxygen levels.[24] Previous studies demonstrated that in cultures performed under 21% O2 (normoxia) both HF mesenchymal (DP and dermal sheath cells)[25] and epithelial[26] populations proliferate at lower rates than when respectively cultured at 6% O2 or 4% O2. Conclusions: Overall, we showed that the response to physoxia differs according to hMel-DP cells interactions and that the microenvironment recreated when in direct contact favours their functions, which can be relevant for hair regeneration purposes

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