The human hair follicle,a bistable organ?

The hair cycle and its control remain today an object of debate. A number of factors, which can modulate this process, have been identified but its choreography remains elusive. For years, the hunt for the conductor has been on, but nobody ever caught him. Intuitively, the process being considered as cyclic, an automaton controlling this cycle should be looked for, by analogy with a clock. However, the putative hair follicle oscillator that would control hair cycle failed to be identified and characterized. In fact, we have revealed that human hair follicle has an autonomous behaviour and that the transitions from one phase to the next occur independently for each follicle, after time intervals given stochastically by a lognormal distribution characterized by a mean and a variance. From this analysis, one can conclude that instead of a cyclical behaviour with an intrinsic automaton, a bistable steady state controls human hair follicle behaviour, which under a stochastic way jumps from the dormant to the active steady state and vice versa.     

Intradermal injections of a hair growth factor formulation for enhancement of human hair regrowth – safety and efficacy evaluation in a first-in-man pilot clinical study

Background: Research has shown the efficacy of hair growth factors in hair regrowth. We describe the intradermal injections of a recombinant, bioengineered hair formulation, containing growth factors, into the scalp skin, for enhancement of hair regrowth and evaluate its efficacy. Objectives: The objective of this study was to assess the efficacy and safety of the hair growth factor formulation in reducing hair loss and enhancing hair growth. Materials and methods: This was an open-label, prospective, single-arm interventional pilot study in which 1000 patients were given intradermal injections of a hair formulation into the scalp skin. The formulation contains vascular endothelial growth factor, basic fibroblast growth factor, insulin-like growth factor, keratinocyte growth factor, thymosin β4, and copper tripeptide-1 suspended in a sterile injectable vehicle. Intradermal injections of this hair formulation were injected into the scalp once every 3 weeks for a total of eight such sessions. Hair pull test was performed before every session. Videomicroscopic and global images were taken at baseline, fourth session, eighth session, and 2 months after the completion of the eight sessions. Relevant safety assessments through physical examination, questionnaires, and appropriate laboratory examination were conducted throughout the study. Results: Significant reduction in hair fall was seen in 83% of the patients on hair pull test. Videomicroscopic image evaluation showed that most patients had a decrease in the number of vellus hairs, increase in number of terminal hairs, and increase in shaft diameter. Seventy-five percent of the patients believed that the hair injections were aiding the treatment of their hair loss, and it was also beneficial in post-hair transplant patients. At 1 year, a statistically significant increase in total hair count (P = 0.002) continued to be seen. Treatment was well tolerated. Conclusions: Intradermal injections of this hair formulation may be a promising option for treating male as well as female patterns of hair loss.     

Microencapsulated human hair dermal papilla cells: a substitute for dermal papilla?

Dermal papillae (DP) play a pivotal role in hair formation, growth and cycling. However, the number of DP is limited. In this study, we report the production of “reconstructed DP” by enclosing DP cells within an alginate–polylysine–alginate (APA) semipermeable membrane. MTT assay and electron microscopy showed that the microencapsulated dermal papilla cells retained normal activity. The microcapsules were implanted into rat footpads, which lack follicles and sebaceous glands, to assess their inductive properties. Histologic examination showed that numbers of follicle and sebaceous gland structures formed in the footpads within 6–10-week period. At the 10 weeks following transplantation, hair fibers were visible in the footpad. These findings indicate that the DP cell microcapsules retain the capacity to initiate follicle regeneration and could be considered a substitute for fresh isolated DPs.     

Why is hair curly?—Deductions from the structure and the biomechanics of the mature hair shaft

The final shape of a head hair is predetermined through a variety of factors during its formation in the follicle. These are genetic pathways, specific growth factors, cell differentiation and segregation, etc, with spatial as well as chronological dynamics. The cortex of hair consists of two major cell groups. These are characterized by parallel (para-type) or roughly helical arrangements (ortho-type) of the intermediate filaments (IF). There are also cell-specific differences in the disulphide content, that is, of the cross-link density of the IF-associated matrix proteins. Given the current state of the academic discussion, we consider it as timely to support and broaden the view that, the structural differences of the cell types together with their lateral segregation are the main driving factor of curl formation. The mechanical effects, which derive thereof, are triggered in the transition zone of the follicle, that is, upon formation of the mature hair shaft. Furthermore, an irregular, “flat” cross section of the hair shaft is shown to be a synergistic but not determining factor of curl formation. The degree of cell type segregation along the mature hair shaft together with dynamic changes of the location of the plane of segregation, namely in a non-circular cross section can account for very complex curl patterns. Against the background of these views, we argue that contributions to hair curl are implausible, if they relate to physical mechanisms which are active below the transition zone from the living to the mature (dead) hair.     

Mechanobiology and cell tensegrity: the root of ethnic hair curling?

Background The hair shape, either straight, crimp, or curly, is basically under genetic influence. It is possibly altered by some drugs such as cytostatic agents. In addition, specific innate molecular characteristics are modulated by some cosmetic procedures to reshape the hair shafts. Aim To revisit the possible implication of mechanobiology and cell tensegrity in shaping ethnic hair. Materials and methods Optical and scanning electron microscopy of hairs. Results It is generally held that the cross‐section shape of hair is related to differences in the global aspect of the hair shaft. A possible biologic link between these features may rely on shaping cell tensegrity at any portion of the hair shaft. Cell tensegrity encompasses all intrinsic and extrinsic forces responsible for the three‐dimensional arrangement of intracellular macromolecules. Conclusion We offer as a hypothesis that the hair shape in part depends on the organization of the cell proliferation in the hair matrix. This review gathers observations supporting the involvement of cell tensegrity in shaping the hair shaft.     

Identification of a cell layer containing α-smooth muscle actin in the connective tissue sheath of human anagen hair

Summary Immunohistochemical and immunoelectron microscopy studies revealed the presence of -smooth muscle (-SM) actin in fibroblasts located in the connective tissue sheath (CTS) of human anagen hair follicles. Immunostaining was positive from the base of the bulb to the upper part of the lower portion of the mature anagen hair follicles. The late catagen hair follicles did not stain. Ultrastructurally, -SM actin was detected only in the fibroblasts located in the innermost layer of the transverse collagenous fibres. Since -SM actin is located in cells with contractile potential, this newly identified layer may play an important role in the morphological changes of the lower portion of the hair follicle during the hair growth cycle.     

Parathyroid hormone‐related peptide and the hair cycle – is it the agonists or the antagonists that cause hair growth?

While the effects of PTHrP have been studied for almost 20 years, most of these studies have focused on effects on the termination of the anagen phase, giving an incomplete picture of the overall effect of PTHrP on the hair cycle. PTHrP was determined in several experimental models to promote transition of hair follicles from anagen to catagen phase, which by itself would suggest that PTHrP blockade might prolong the anagen phase and promote hair growth. However, clinical trials with topically applied PTHrP antagonists have been disappointing, leading to a reconsideration of this model. Additional studies performed in mouse models where hair follicles are damaged (alopecia areata, chemotherapy‐induced alopecia) suggest that PTHrP has effects early in the hair cycle as well, promoting hair follicles’ entry into anagen phase and initiates the hair cycle. While the mechanism of this has yet to be elucidated, it may involve activation of the Wnt pathway. Thus, the overall effect of PTHrP is to stimulate and accelerate the hair cycle, and in the more clinically relevant models of hair loss where hair follicles have been damaged or become quiescent, it is the agonists, not the antagonists, which would be expected to promote hair growth.     

Association between smoking and hair loss: another opportunity for health education against smoking?

Besides being the single most preventable cause of significant morbidity and an important cause of death in the general population, tobacco smoking has been associated with adverse effects on the skin. Smoke-induced premature skin ageing has attracted the attention of the medical community, while only recently an observational study has indicated a significant relationship between smoking and baldness. The mechanisms by which smoking causes hair loss are multifactorial and are probably related to effects of cigarette smoke on the microvasculature of the dermal hair papilla, smoke genotoxicants causing damage to DNA of the hair follicle, smoke-induced imbalance in the follicular protease/antiprotease systems controlling tissue remodeling during the hair growth cycle, pro-oxidant effects of smoking leading to the release of pro-inflammatory cytokines resulting in follicular micro-inflammation and fibrosis and finally increased hydroxylation of oestradiol as well as inhibition of the enzyme aromatase creating a relative hypo-oestrogenic state. In view of the psychological impact of androgenetic alopecia on affected men and women, increasing public awareness of the association between smoking and hair loss offers an opportunity for health education against smoking that may be more effective than the link between smoking and facial wrinkles or grey hair, since the latter can be effectively counteracted by current aesthetic dermatologic procedures, while treatment options for androgenetic alopecia are limited.     

Is the loose anagen hair syndrome a keratin disorder? A clinical and molecular study

OBJECTIVES: To report the clinical features of the loose anagen hair syndrome and to test the hypothesis that the typical gap between the hair and the inner root sheath may result from hereditary defects in the inner root sheath or the apposed companion layer. DESIGN: Case series. SETTING: A pediatric dermatology unit (referral center). PATIENTS: A consecutive sample of 17 children (13 girls). For 9 of them and their first-degree relatives, molecular analyses were performed in the K6HF gene with 50 appropriate controls. INTERVENTION: Minoxidil therapy (5% lotion) in 11 patients for 1 to 12 months. MAIN OUTCOME MEASURES: Clinical and follow-up features and determination of mutations in the K6HF gene. RESULTS: Most patients had easily pluckable hair with no sign of scalp inflammation or scarring. Ten patients seldom cut their hair, and 4 had unmanageable hair. One patient had hypodontia. Two patients had an additional clinical phenotype of diffuse partial woolly hair. The family history was positive for loose anagen hair syndrome in 5 patients. Marked improvement was noted after treatment with 5% minoxidil lotion in 7 of the 11 patients treated. Polymerase chain reaction analysis of the gene segments encoding the alpha-helical 1A and 2B subdomains of K6hf, the type II cytokeratin exclusively expressed in the companion layer, was performed in 9 families. In 3 of these 9 families, a heterozygous glutamic acid and lysine mutation, E337K, was identified in the L2 linker region of K6HF. CONCLUSIONS: Diffuse partial woolly hair can be associated with loose anagen hair syndrome. A keratin mutation, E337K in K6HF, was possibly causative in 3 of the 9 families studied. Another keratin, and possibly the type I partner of K6hf, could be responsible for loose anagen hair syndrome in other patients, or the gene involved may be a minor gene.     

What do gay men know about human papillomavirus? Australian gay men's knowledge and experience of anal cancer screening and human papillomavirus

OBJECTIVE: The objective of this study was to determine levels of experience and knowledge concerning anal dysplasia, anal Pap smear tests, and human papillomavirus (HPV) among gay and other homosexually active men. STUDY DESIGN: Three hundred eighty-four men attending a large gay community event in Melbourne completed a short survey. RESULTS: Ninety-two percent identified as gay and 4.8% as bisexual. A total of 6.4% were HIV-positive and a further 3.5% did not know their HIV status. On a range of measures, it was clear that the men knew very little about anal cancer (19% scored zero on a 12-point knowledge scale) and virtually nothing about HPV (47% scored zero on an 8-point knowledge scale). A total of 55.1% had never heard of an anal Pap smear and 44.8% had ever heard of HPV; 56.4% did not know whether it affected men and/or women. CONCLUSIONS: The test for anal dysplasia is still largely unknown among Australian gay men and they currently have poor sense of personal susceptibility to the disease. Health education strategies are suggested to improve this situation.     

Calcitonin gene-related peptide (CGRP) may award relative protection from interferon-γ-induced collapse of human hair follicle immune privilege

Interferon-γ (IFNγ)-induced collapse of hair follicle (HF) immune privilege (IP) is a key element in the pathogenesis of alopecia areata. In this pilot study, we investigated whether the immunosuppressive neuropeptide, calcitonin gene-related peptide (CGRP), can protect from and/or restore IFNγ-induced HF-IP collapse. After showing that human scalp HFs express CGRP receptor-like receptor (CRLR) immunoreactivity, anagen HFs were cultured in the presence of IFNγ, with CGRP added before or after. Adding CGRP after IFNγ administration ('restoration assay') failed to downregulate IFNγ-induced ectopic MHC class I expression, while MHC class II expression was reduced. However, administering CGRP before IFNγ application ('protection assay') significantly reduced the IFNγ-induced overexpression and ectopic expression of MHC class I and II and reduced the increased degranulation of perifollicular mast cells induced by IFNγ. This suggests that CGRP may not restore HF-IP once it has collapsed, but may protect it from collapsing. Therefore, CRLR stimulation might help to retard AA progression.     

What s new in hair transplants?

As hair transplant surgery has evolved, combinations of micrografting and minigrafting have enabled physicians to produce ever more natural combinations of both. A wide range of men and women can now receive significant aesthetic benefits from hair transplants. In recent years, practitioners have further refined hair transplant techniques to ensure that the hairs available for transplantation are used most efficiently. Specifically, methods of harvesting hair, preparing grafts, creating recipient sites, and placing grafts are designed to permit the maximum percentage of hairs to survive and thrive after transplantation. Careful planning, close cooperation with the patient, and a staged surgical approach can also result in hair conservation and optimal cosmesis.