What’s new in hair — December 2016 | Dr. Claire A. Higgins

Long-term efficacy and safety of the dual 5-alpha reductase blocker dutasteride on male androgenetic alopecia patients

J Dermatol. 2016 Dec 18. doi: 10.1111/1346-8138.13710. [Epub ahead of print]

Finasteride is a 5-alpha reductase inhibitor, which is FDA approved for the treatment of androgenetic alopecia. More recently, dutasteride has been proposed as a treatment for androgenetic alopecia. Dutasteride, which is also a 5-alpha reductase inhibitor has been licensed for the treatment of androgenetic alopecia both in South Korea and Japan, however, it is not currently approved for the treatment of hair loss in either Europe or the USA. In this manuscript, Chung et al conduct a retrospective review of dutasteride safety, in 26 Korean men who took 0.5mg daily for >52 months. Assessing a range of lab test results including haemoglobin levels, alanine aminotransferase levels, and testosterone levels no significant changes were observed before or after taking dutasteride. The only lab result where a significant difference was observed was cholesterol, which increased, however this was still within a normal range. The number of terminal hairs also increased, however not significantly. Despite this, patients were significantly less emotional (emotional score) after treatment. This may either be because they have an improved perception of themselves, or perhaps they are happy they are receiving treatment. In conclusion, the authors found no significant side effects in patients who used dutasteride for >52 months.

 

Hair pull test: Evidence-based update and revision of guidelines

J Am Acad Dermatol. 2016 Dec 20. pii: S0190-9622(16)30892-1. doi: 10.1016/j.jaad.2016.10.002. [Epub ahead of print]

When a patient presents with hair loss, a clinical evaluation is required to determine the type of alopecia exhibited. Clinical tests, such as the ‘hair pull test’ can be used to evaluate whether hairs are ‘loose’. In this, the clinician will take a bundle containing 50-60 hairs, and gently pull along their length from the root to the tip. Current guidelines recommend that the patient does not wash their hair for 5 days preceding the test, and if >10% of the hairs in the bundle come loose with the pull, then the patient may have telogen or anagen effluvium. In this study, McDonald and colleagues re-evaluated the present guidelines for the hair pull test. They conducted the hair pull test on the scalp vertex of 181 patients without hair loss, and looked to see if there were any differences in the number of hairs removed in patients with different ethnicities, sexes, ages, types of hair (curly, wavy or straight), hair textures, or styling practices. In addition, they evaluated patients who had not washed or brushed their hair since the morning of the test, since the day before, or for two or more days. They concluded that there were no significant differences in the number of hairs removed in any of the categories, and suggest that the restrictions on hair washing before testing should be removed. One interesting observation made in this study, was that the number of hairs removed from these healthy patients per hair pull was very low. The authors therefore also suggest that the guidelines should be reformatted, and that if >5% of hairs within a bundle are removed in a hair pull test, then this should indicate the onset of alopecia.

 

Identification of key genes induced by platelet-rich plasma in human dermal papilla cells using bioinformatics methods

Mol Med Rep. 2017 Jan;15(1):81-88. doi: 10.3892/mmr.2016.5988. Epub 2016 Dec 6

Platelet rich plasma (PRP) is becoming a popular ‘alternative’ treatment for androgenetic alopecia, especially in patients who have not responded to either minoxidil or finasteride. Despite this, its mechanism of action on the follicle remains unknown. In this study, Shen et al placed 5% PRP onto human hair follicle dermal papilla cells in vitro, followed by RNA-Sequencing and bioinformatics analysis to identify differentially regulated genes and pathways. They identified 507 genes which were differentially regulated by the application of PRP; 365 of these increased in expression while 142 decreased in PRP treated samples compared to controls. When KEGG pathways were assessed, a significant number of up-regulated genes were associated with ‘cell cycle’, ‘progesterone mediated oocyte maturation’ and ‘DNA replication’. While the authors did not look to see if this corresponded with an increase in dermal papilla cell proliferation in vitro, it is likely that PRP affects cell division given the increase in genes associated with the cell cycle after PRP treatment.

 

Hair follicle stem cell cultures reveal self-organizing plasticity of stem cells and their progeny

EMBO J. 2016 Dec 9. pii: e201694902. [Epub ahead of print]

A stem cell niche is defined as a microenvironment which regulates stem cell fate. It is always anatomically close to the stem cell population, and can be either extracellular or cellular in nature. When epidermal cells are isolated from telogen mouse skin, 5.6% of these cells are hair follicle stem cell (HFSCs), however, when these isolated epidermal cells are cultured in normal culture conditions the HFSC population is depleted. In this study, Chacón-Martínez et al sought to develop an in vitro culture system which would recapitulate the HFSC niche, and thus maintain these stem cells in culture for longer. They found that when cells were cultured in a 3D microenvironment, containing laminin rich matrigel, and supplemented with FGF2, VEGFA and a Rock Inhibitor, they were able to maintain growth of HFSC in cultures of isolated epidermal cells. RNA-Sequencing to compare the epidermal cells from which the 3D cultures were established, 3D cultures themselves, and FACs sorted HFSC showed there was a 40% overlap between the FACs sorted HFSCs, and 3D cultures of epidermal cells, indicating an enrichment of HSFCs induced by the 3D culture microenvironment. On analysis, the authors found that this 40% transcriptome overlap was due to the establishment of a 50:50 population equilibrium of HSFCs and non-HSFCs within the 3D culture microenvironment. They showed that cells are able to transition from one state to the other, maintaining the population equilibrium, which is controlled via BMP and Shh signalling. Thus, in this manuscript the authors demonstrate the minimal essential components of the HFSC niche, which can be used to develop a tuneable system for the study of HSFCs in vitro.

 

Genomic expression differences between cutaneous cells from red hair color individuals and black hair color individuals based on bioinformatic analysis

Oncotarget. 2016 Dec 24. doi: 10.18632/oncotarget.14140. [Epub ahead of print]

Hair pigmentation depends on the relative amounts of eumelanin and pheomelanin in melanosomes of the follicle, which are produced and released by hair follicle melanocytes. Melanin production is controlled by the melanocortin receptor type 1 (MC1R) gene, and it is well known that loss of function mutations in MC1R result in melanocytes producing predominantly pheomelanin, which leads to the red hair phenotype. In addition, pheomelanin is not as suitable a UV shield as eumelanin, and as a result of this red haired individuals have an increased risk for melanoma and non-melanoma skin cancers. In this manuscript, Puig-Butille et al took a list of 3570 genes which they had previously identified in transcriptome analysis, and conducted further Protein-Protein Interaction (PPI) network analysis. The 3570 genes were identified by comparing gene expression profiles of co-cultured keratinocytes and melanocytes from red haired individuals with a loss of function mutation in MC1R, against co-cultured keratinocytes and melanocytes from individuals with wild-type MC1R. The PPI network analysis generated two networks; one containing 557 nodes representing up-regulated genes, and a second network with 450 nodes representing down-regulated genes. When the authors conducted centrality analysis they were able to identify hub nodes within these networks; 13 in the up-regulated network which have a role in DNA repair and cell-cycle homeostasis (PRKAA1, CDK1, BUB1B, PCNA, RPA1 and BRCA1), oxidative phosphorylation (GBAS, ICT1) and autophagy (PIK3C3, ATG4C, ATG10 and SNX2), and 11 in the down-regulated network which are known to be involved in apoptosis (SMAD3, YWHAG), mRNA metabolism (PABPC1), and autophagy (TRAF2, SQSTM1, CLN3, WIPI2, GABARAPL1, GABARAPL2, MAP1LC3B, MAP1LC3A). The authors next obtained transcriptome data from the TwinsUK MuTHER dataset, and assessed expression of these hub nodes in whole skin biopsies from 13 red haired individuals and 7 black haired individuals. Of the 23 genes, only 18 were included within the dataset, however, when differential analysis was restricted to individual genes the authors found significant differences between red and black haired individuals in 8/18 genes. Interestingly, when they looked at melanoma samples from red haired and black haired individuals, no differences were detected in any hub genes.

 

EMILIN3, an extracellular matrix molecule with restricted distribution in skin

Exp Dermatol. 2016 Nov 28. doi: 10.1111/exd.13254. [Epub ahead of print]

EMILINS (Elastin Microfibrils Interface Located proteINS) are a family of extracellular matrix glycoproteins, however, their functions remain largely unknown. In this paper, Corallo et al assess the distribution and function of Emilin3, in the skin and hair follicle of mice. They find that at birth, Emilin3 is distributed throughout the papillary dermis, and using immunoelectron microscopy demonstrated that it decorates Fibrillin-1 microfibrils. Intriguingly, when mice are 10 days old, and follicles are in mid-anagen, Emilin3 expression disappears from the dermis, and becomes restricted to the hair follicle bulge, just adjacent to the insertion point of the arrector pili muscle. The authors generated an Emilin3 knockout mouse, however they did not identify any gross differences in hair follicle cycling, hair follicle or sebaceous gland morphology. Either Emilin3 does not have a role within the hair follicle, there is compensation from other extracellular matrix proteins within the follicle, or the differences are subtle and yet to be identified.

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