What’s new in hair — October 2016 | Claire A Higgins

A Comparative Study of Oral Cyclosporine and Betamethasone Minipulse Therapy in the Treatment of Alopecia Areata.

Ann Dermatol. 2016 Oct;28(5):569-574

Alopecia areata is an autoimmune disease that results in loss of hair on the scalp and body.  Treatment can be topical if patches are localised, or systemic if alopecia is more severe.  However, there is no definitive systemic treatment schedule suggested for use for patients.  In this study, Jang et al performed a retrospective analysis to compare the efficacy and safety of two systemic treatments for alopecia areata; oral cyclosporine and betamethasone minipulse therapy.  They assessed 88 patients, 51 of whom had received cyclosporine, and 37 who received betamethasone minipulse therapy.  Hair regrowth after treatment was 52.9% in the cyclosporine group, which was slightly higher than the 45.9% observed in the betamethasone minipulse therapy group.  While this difference was not significant, when patients were asked to evaluate the quality of their hair regrowth, there were significantly more patients in the cyclosporine group compared to the betamethasone minipulse therapy group (70.6% vs 43.2%) who were happy with the results.  When patients were stratified according to the severity of disease, or the duration of disease, there were no significant differences between treatments.  When the authors looked at age of onset as a stratifying factor, they found no differences between patients treated with cyclosporine, however, in the betamethasone minipulse therapy group significantly more patients responded to treatment when their age of disease onset was over 30 (approximately 60% vs 20%).  This difference in age response may account for the lower efficacy observed with betamethasone minipulse therapy when patients were not stratified according to the age of onset, and highlights the importance of patient stratification in clinical trial design.  This retrospective study also suggests that oral cyclosporine is a more effective treatment for alopecia areata, however as the authors point out, larger controlled studies will need to be performed going forward.

 

Solid effervescent formulations as new approach for topical minoxidil delivery.

Eur J Pharm Sci. 2016 Oct 13;96:411-419. doi: 10.1016/j.ejps.2016.10.016.

There are two FDA approved drugs for the treatment of androgenetic alopecia; minoxidil and finasteride.  Only minoxidil is approved for topical use, however patients often complain that it leaves a hard greasy coating on the hair shaft, while it has also been known to cause skin irritation.  Patients are required to apply the product twice daily, and this combined with the undesirable sensorial aspects means there is often a lack of patient compliance.  Minoxidil sulphate (MXS) is the active ingredient in minoxidil, and several groups have looked at altering the formulation of MXS for better follicle targeting.  In this study, Pereira et al assessed whether effervescent formations of MXS would penetrate skin and hair follicles better than solid or liquid formulations.  They hypothesised that MXS administered as an effervescent powder would, when hydrated, penetrate the skin better due to increased thermodynamic activity, and mechanical movement caused by the effervescence.  They manufactured four effervescent formulations with varying particle sizes and disintegration times.  Next, they applied these formulations to porcine skin, followed by the addition of water.  Comparisons were made with MXS in liquid form, and MXS in solid form plus water.  Solutions were left on the skin for 3hrs, after which time the skin was washed, tape stripped to remove the stratum cornuem, and analysed for the presence of MXS.  The authors found that two of the formulations resulted in a significant increase (4-fold) of MXS in the remaining skin, compared to the solid or liquid state controls.  This suggests that effervescent technology can indeed aid penetration of MXS into the skin, however, the challenge now lies in developing an effervescent product that would be simple for patients to use.

 

Stem Cell Markers (Cytokeratin 17 and Cytokeratin 19) in Scarring and Nonscarring Alopecia.

J Cutan Aesthet Surg. 2016 Jul-Sep;9(3):165-171.

There are many types of alopecia’s, ranging from alopecia areata through to androgenetic alopecia.  Alopecia’s can be categorised into either scarring (cicatricial) alopecia’s, or non-scarring (non-cicatricial), with both alopecia areata and androgenetic alopecia falling in the latter category.  In this study, El Sakka et al assessed the expression of cytokeratins 17 and 19 in hair follicles of 10 control patients, 15 scarring alopecia’s, and 15 nonscarring alopecia’s.  For nonscarring alopecia’s, patients with alopecia areata were used, while for the scarring cohort they obtained follicles from 5 patients postburn, 5 patients with old scarring discoid lupus erythematous, and 5 patients with old scarring lichen planopilaris.  The most interesting finding was that while CK17 was expressed in both control follicles, and nonscarring alopecia follicles, expression was significantly decreased (or absent) in follicles from patients with scarring alopecia’s.  CK17 is a cytoskeletal protein found in the outer root sheath of hair follicles, and in mice at least the loss of this protein results in premature catagen entry and hair loss.

 

Activin A-induced signaling controls hair follicle neogenesis.

Exp Dermatol. 2016 Oct 10. doi: 10.1111/exd.13234.

The dermal papilla is a small cluster of cells located at the base of the hair follicle, and in the adult it retains a capacity to induce new hair growth.  When human dermal papillae are removed from hair follicles, and the cells are grown in culture they lose this hair inducing ability.  However, in recent years it has been shown that human dermal papilla cells regain their inductive capacity when they are grown in 3D conformations, namely, as dermal spheroids.  In this paper, Seo et al evaluated the secretome of human dermal papilla spheres, to determine whether they produce specific factors that may activate or influence epithelial cells.  Using a proteomic array to assess the proteins secreted into the culture media they found that Activin A, a member of the TGFβ superfamily, was released by dermal papilla spheroids, but not by cells in 2D cultures.  They demonstrated that Activin A was necessary for spheroid inductivity, as when it was knocked down using siRNA spheroids lost their ability to induce new hair growth.  However, recombinant Activin A did not increase the inductivity of papilla spheroids, and its’ expression alone is therefore not sufficient for induction.  This is an interesting paper that helps uncover how dermal papilla cells in 3D, but not 2D, are inductive.

 

Single-Cell Transcriptomics Reveals that Differentiation and Spatial Signatures Shape Epidermal and Hair Follicle Heterogeneity.

Cell Syst. 2016 Sep 28;3(3):221-237.e9. doi: 10.1016/j.cels.2016.08.010.

Hair follicle stem cells were first described in the early 1990’s, and since then several subpopulations of stem cells have been detected within the hair follicle, which give rise to other structures such as the sebaceous gland, and infundibulum.  Given the increasing number of detected stem cell compartments we know this tissue is highly complex, yet until now the tools to detect all the stem cell subpopulations has remained elusive.  In this manuscript, Joost et al use single cell RNA sequencing to deconvolute the transcriptome of all the cells in the epithelial compartment of the murine hair follicle (in telogen), and the interfollicular epidermis. They sequenced 1422 single cells and revealed 25 distinct clusters of cells in the skin epithelium.  Within the epidermis they found a number of well-established populations, including Langerhans cells, T cells, and the basal, differentiated and keratinized layers of the skin.  They used elegant bioinformatics approaches to create pseudo-temporal maps to mark how a cell transitions from the basal layer of the epidermis through to the stratum corneum.  In the hair follicle, they identified 16 subpopulations, including a number of new stem cell populations.  They have provide a number of online resources to supplement their paper, including an atlas which can be used to interrogate distinct cell types within murine epithelium.  These tools will enable the stem cell research community to further dissect the functions, and roles of individual cell types within a heterogeneous tissue.

 

Androgens modify Wnt agonists/antagonists expression balance in dermal papilla cells preventing hair follicle stem cell differentiation in androgenetic alopecia.

Mol Cell Endocrinol. 2016 Oct 18;439:26-34. doi: 10.1016/j.mce.2016.10.018.

It is well established that cross talk between the dermal papilla and hair follicle stem cells (HFSC) is essential for hair growth.  When grown in culture, human dermal papilla cells can elicit expression of K6hf (K75) in HFSC, indicating transition of these stem cells to a differentiated state.  Assessing this transition can serve as a good model for hair growth, since balding dermal papilla cells are unable to initiate K6hf expression in HFSC in vitro.  In this paper, Leirós et al used a stable androgen response human dermal papilla cell line, to evaluate if androgens could affect the ability of dermal papilla cells to elicit HFSC differentiation in vitro.  They found that the addition of DHT to dermal papilla cultures resulted in increased Dkk1 (a wnt inhibitor), and decreased Wnt10b and Wnt5a.  This in turn decreased the ability of dermal papilla cells to initiate expression of K6hf in HFSC.  Since DHT seemed to be inhibiting wnt signalling, which is known to be essential for hair growth, they looked to see whether the addition of Dkk1 to dermal papilla cultures would have the same effect.  They found that adding Dkk1 to papilla cultures to inhibit wnt signalling also blocked the ability of papilla cells to initiate HFSC differentiation.  Comparatively, when they added Wnt10b to papilla cultures with DHT, they found that this was sufficient for dermal papilla cells overcome the inhibitory effect of DHT, to initiate HFSC differentiation.  This paper demonstrates that a stable androgen response human dermal papilla cell line, with DHT, can reliably mimic the effect of balding dermal papilla cells in vitro.  It also suggests that DHT may result in transition from a ‘non-balding’ to a ‘balding’ dermal papilla by inhibiting wnt signalling.

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