What’s new in hair — December 2015 | Dr. Claire A. Higgins

α1 -AR agonist induced piloerection protects against the development of traction alopecia.

Dermatol Ther. 2015 Dec 17. doi: 10.1111/dth.12324.

Traction alopecia arises as a result of excessive forces on the hair follicle.  This mechanical trauma often arises as a result of hair styling practices, such as blow drying and use of hair straighteners.  The tension applied to the follicle during styling, resulting in epilation, is in the opposite direction of the tension applied to the follicle by contraction of the arrector pili muscle.  In this study, Goren et al hypothesised that when an arrector pili muscle is contracted, more force would be required to remove a hair fiber from the follicle compared to a resting state.  They treated 15 patients with placebos or 10% phenylephrine (which promotes arrector pili muscle contraction), and assessed hair fall during brushing, and the force required to pluck hair fibers from the follicle.  They find on average there is a 42% reduction in hair fall during brushing when phenylephrine is applied to stimulate arrector pili muscle contraction.  Using a trichotillometer to calculate force, they also show that a 172% increase in force is required to pluck fibers from the follicle when scalp is treated with topical phenylephrine compared to a placebo.  This intriguing study demonstrates that counteracting the direction of tension applied to the follicle during styling may promote shaft retention, and benefit patients with traction alopecia.

 

Global divergence of the human follicle mite Demodex folliculorum: Persistent associations between host ancestry and mite lineages.

Proc Natl Acad Sci U S A. 2015 Dec 29;112(52):15958-63. doi: 10.1073/pnas.1512609112.

Two species of the microscopic mite of the genus Demodex live in human hair follicles; Demodex folliculorum resides within the hair follicle pore, while Demodex brevis is found in the sebaceous gland.  In this study, Palopoli et al sequenced a 930bp fragment of the genome of D. folliculorum in 70 human hosts of diverse ancestries currently living in the United States.  They discovered four genetically divergent lineages of D. folliculorum termed clades A, B, C and D in the 70 hosts.   Interestingly, this molecular variation segregated according to the regional ancestry of the hosts, and was highly unlikely to have occurred by chance (p<0.000001). Hosts of African descent harboured mites from all 4 clades, while European descendants harboured mites predominantly from clade D.  Hosts of Asian descent harboured mites from clades A, B and D, but not C.   Importantly, some of the hosts sampled had lived in the United States for several generations, but still harboured mite populations in clades in line with their regional ancestry.  The authors proposed a ‘skin trait’ model, arguing that differences in the hair follicle, such as density and morphology, between different ancestries has resulted in the persistence of specific mite populations as a result of differential survival rather than mite colonisation.

 

Comparison between hair follicles and split-thickness skin grafts in cutaneous wound repair.

Int J Clin Exp Med. 2015 Sep 15;8(9):15822-7.

It has long been noted that wound healing occurs faster in terminal hair bearing sites compared to glabrous sites on the body.   In light of this, Jiménez et al previously demonstrated that hair follicle biopsies could promote wound closure in non-healing leg ulcers (1).  However, no direct comparisons were made between hairy biopsies and split-thickness skin grafts.  In this study, Yang et al treated 40 patients with chronic cutaneous wounds with either terminal hair follicle biopsies, or split thickness skin grafts (20 in each cohort).  They then used 5 blinded reviewers to assess healing duration, skin quality and scar quality after healing.  While there were no significant differences in healing duration between cohorts, the reviewers found skin quality on the chronic wound to be statistically superior in patients who received hair follicle therapy compared to split thickness graft treatment (p<0.05).  They also noted that unlike hair transplantation, hair shafts were rarely noted at the recipient site.  The main questions now are how does the follicle promote wound closure of chronic wounds, and can this be translated to clinical practice?

 

Biomarkers of alopecia areata disease activity and response to corticosteroid treatment.

Exp Dermatol. 2015 Dec 14. doi: 10.1111/exd.12918.

In active alopecia areata (AA) there is both a strong cytotoxic T cell (CTL) presence, and a large amount follicle inflammation, resulting in high CTL and inflammatory signatures associated with disease.  Previously, Xing et al used CTL and interferon (IFN) signatures associated with the disease to develop an ALADIN score which can be used to monitor both progression and reversal of hair loss (2).  They specifically focused on long standing disease and treatment with Janus kinase inhibitors.  In patchy AA, intralesional steroid injection is a standard treatment, however, success rates can be variable.  In this study Fuentes-Duculan et al characterised biomarkers of AA in 5 patients with patchy disease before and after successful treatment by corticosteroid injection.  They also compared lesional and non-lesional sites prior to treatment, and found that IL-12/IL-23 p40, and IL-32 were significantly increased in AA lesions before treatment.  These cytokines all decreased in scalp correlating with hair regrowth after treatment, as did CD3+ and CD8+ T-cells, CD11c+ dendritic cells and CD1a+ Langerhans cells.  They went on to show that IL-32 is produced by both CD3+ and CD8+ CTLs, suggesting a potential role for IL-32 in disease pathogenesis.  It would be interesting to assess these same biomarkers in patients who do not show regrowth after corticosteroid injection, to see if it is possible to predict responders and non-responders.

 

Cytokine loaded layer-by-layer ultrathin matrices to deliver single dermal papilla cells for spot-by-spot hair follicle regeneration.

J Mater Chem B. 2015 Dec 10; doi: 10.1039/C5TB02265G

The dermal papilla (DP) is a small mesenchymal compartment located at the base of the follicle, with an indispensable role in hair growth.  Conventionally, DP cells are grown in 2D cultures, which lack the native micro environmental cues present within the follicle niche.  In this study, Lin et al use a novel layer-by-layer (LBL) encapsulation approach, to coat single mouse vibrissae DP cells with nano scale extracellular matrix.  This matrix consisted of gelatin and alginate, forming an approximately 7µm layer around individual DP cells.  While DP cells normally flatten out on the bottom of a culture dish, these encapsulated DP cells ‘sat up’, and grew as little spheroidal cells rather than flattened structures.  Encapsulation did not appear to impact cell proliferation or cell viability, and actually reduced αSMA expression, suggesting the cells were reverting to an in vivo phenotype when encapsulated.  The authors also demonstrate that growth factors, such as FGF2, can be incorporated into the nano-coating.  While encapsulation alone did not alter the inductive potential of these DP cells, nano-coating incorporating FGF2 significantly increased inductivity of DP cells compared to FGF2 alone in 2D cultures.  This LBL approach will be interesting to elucidate the role of individual growth factors, and temporal release of growth factors on DP cells in culture.

Embryonic attenuated Wnt/β-catenin signaling defines niche location and long-term stem cell fate in hair follicle.

Elife. 2015 Dec 14;4. pii: e10567. doi: 10.7554/eLife.10567

Hair follicles arise as a result of reciprocal interactions between the mesenchyme and overlying epithelium.  During development, we first see formation of an epithelial placode then a hair germ, later a hair peg before formation of an adult follicle.  Hair follicle stem cells reside in the bulge, which is formed at the completion of development.  This raises the question; do bulge cells arise from progenitor cells that acquire stem cell fate, or are they remnants of embryonic progenitors that maintain stem cell potential?  In this paper, Xu et al seek to answer this question, and start by using elegant transgenic models to selectively label, and follow the fate of cells in the placode, germ and hair peg.   The first find that bulge cells arise from progenitors present in upper hair peg, but not in the broader populations of the placode or germ.  When they use a two-photon laser to ablate these upper peg cells, they found de novo bulge formation occurred, suggesting that it is not the cells themselves, but their location that determines stem cell specification.  Importantly, they demonstrate that attenuation of Wnt signalling within the niche enables this spatial specification of bulge stem cell progenitors in the upper hair peg during development.  Since stem cell precursors can be replaced after ablation by new cells occupying the same position, it suggests that long range Wnt inhibitors may have a role in specifying the niche location during development.

References

1. A pilot clinical study of hair grafting in chronic leg ulcers.
Wound Repair Regen. 2012 Nov-Dec;20(6):806-14. doi: 10.1111/j.1524-475X.2012.00846.x.
2. Alopecia areata is driven by cytotoxic T lymphocytes and is reversed by JAK inhibition.
Nat Med. 2014 Sep;20(9):1043-9. doi: 10.1038/nm.3645.

 

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