Hair Growth Cycle Research Articles

Neural Potential of a Stem Cell Population in the Hair Follicle

The bulge region of the hair follicle serves as a repository for epithelial stem cells that can regenerate the follicle in each hair growth cycle and contribute to epidermis regeneration upon injury. Here we describe a population of multipotential stem cells in the hair follicle bulge; these cells can be identified by fluorescence in transgenic nestin-GFP mice. The morphological features of these cells suggest that they maintain close associations with each other and with the surrounding niche. Upon explantation, these cells can give rise to neurosphere-like structures in vitro. When these cells are permitted to differentiate, they produce several cell types, including cells with neuronal, astrocytic, oligodendrocytic, smooth muscle, adipocytic, and other phenotypes. Furthermore, upon implantation into the developing nervous system of chick, these cells generate neuronal cells in vivo. We used transcriptional profiling to assess the relationship between these cells and embryonic and postnatal neural stem cells and to compare them with other stem cell populations of the bulge. Our results show that nestin-expressing cells in the bulge of the hair follicle have stem cell-like properties, are multipotent, and can effectively generate cells of neural lineage in vitro and in vivo.

Mechanisms of Laser Hair Removal

BACKGROUND Current laser hair removal modalities achieve a long-term but not persistent (irreversible) hair loss. OBJECTIVE This review highlights the mechanisms of the current laser hair removal technology and explores possible side effects. METHODS The literature is reviewed. RESULTS The hair shaft plays a key role in the mechanisms underlying current photoepilation procedures by acting as a vector for heat transfer. Together with inherent properties of the hair growth cycle and the anatomic specifics of the follicular stem cells located in the bulge, the crucial role of the hair shaft and its lack of complete destruction with present technology are also likely culprits for the nonpersistent nature of present laser hair removal. Future persistent photoepilation may be associated with vitiligo or vitiligolike changes. Disturbances in wound repair of previously lasered sites are less likely. CONCLUSIONS The currently available laser hair removal protocols are safe, not the least because they achieve long-term but not persistent epilation. The adverse effects of persistent laser hair removal technology possibly available in the future are potentially problematic.

Evaluation of the permeability of hair growing ingredient encapsulated PLGA nanospheres to hair follicles and their hair growing effects

This paper describes the process of encapsulating hair growing ingredients in the PLGA nanospheres by emulsion solvent diffusion method and investigates the feasibility of using the PLGA nanospheres as the DDS (Drug delivery System) carriers for delivering various hair growing ingredients to hair follicles. In-vitro and in-vivo tests were conducted to verify the performances of encapsulated PLGA nanospheres with three different hair growing ingredients. In the in-vitro tests, the scalp-pore permeability of hair growing ingredient encapsulated PLGA nanospheres (dispersed in the PBS solution) was examined using human scalp biopsies in a modified Bronaugh diffusion chamber in comparison to that of the control samples containing the hair growing ingredient in the PBS solution. Furthermore, the hair growing effect of the encapsulated PLGA nanospheres was evaluated with the C3H mice in the in-vivo tests. By observing the fluorescence intensity of the ingredients, as shown in the cross-section photographs of the human scalp biopsies, it was found that the dispersion liquids containing hair growing ingredient encapsulated PLGA nanospheres exerted a scalp-pore permeability 2.0- to 2.5-fold more marked than that of the control samples. Also, the hair growing activities were enhanced by using the encapsulated PLGA nanospheres, which transformed the hair growth cycle from the resting phase to the growing phase. As a result, the degree of hair growth was improved significantly. These results suggested that the PLGA nanosphere can be a new DDS carrier for delivering hair growing ingredients and drugs to the hair follicles.

Mechanisms of Laser Hair Removal: Could Persistent Photoepilation Induce Vitiligo or Defects in Wound Repair?

Current laser hair removal modalities achieve a long-term but not persistent (irreversible) hair loss. This review highlights the mechanisms of the current laser hair removal technology and explores possible side effects. The literature is reviewed. The hair shaft plays a key role in the mechanisms underlying current photoepilation procedures by acting as a vector for heat transfer. Together with inherent properties of the hair growth cycle and the anatomic specifics of the follicular stem cells located in the bulge, the crucial role of the hair shaft and its lack of complete destruction with present technology are also likely culprits for the nonpersistent nature of present laser hair removal. Future persistent photoepilation may be associated with vitiligo or vitiligolike changes. Disturbances in wound repair of previously lasered sites are less likely. The currently available laser hair removal protocols are safe, not the least because they achieve long-term but not persistent epilation. The adverse effects of persistent laser hair removal technology possibly available in the future are potentially problematic.

Biological and environmental degradation of gorilla hair and microsatellite amplification success

Naturally shed hairs are an important source of genetic material for both conservation and forensics but are notoriously poor sources of DNA. DNA degradation in hair roots is caused by apoptosis as part of the cycle of hair growth and by autolysis in decomposing animals. Shed hairs are additionally exposed to degenerative environmental processes. However, genetic studies rarely examine hair root morphologies or refer to root growth phases prior to analysis, and detailed knowledge of the rapidity of DNA degradation amongst shed hairs is lacking. We examined the effects of biological and environmental processes on western lowland gorilla (Gorilla gorilla gorilla Savage and Wyman) hair roots with respect to morphological characteristics and polymerase chain reaction (PCR) success at eight nuclear loci. Root type frequencies indicate that gorilla body hairs may exhibit a longer telogen phase than human head hairs. All plucked hair root types amplified more efficiently than shed hairs, and only 41% of shed hairs had root types considered suitable for genotyping. Telogen hairs from fresh nests were four-fold more useful for genotyping if the roots were associated with translucent epithelial tissue, and preselection of these root types doubled the overall data-yield to 58%. Nest age correlated with root morphology and PCR success, and PCR success was almost halved after 3 days of exposure. Finally, an association between postmortem interval, root morphology, and PCR success was observed that was consistent with postmortem changes reported in human head hairs.

Development and evaluation of polyherbal formulation for hair growth–promoting activity

Cuscuta reflexa (Roxb.), Citrullus colocynthis (Schrad.), and Eclipta alba (Hassk.) are traditionally acclaimed herbs for their hair growth-promoting potential. Aim In the present study, it was envisaged to prepare herbal formulations containing petroleum ether extracts of the three herbs in varying ratio and evaluating the formulations for the hair growth-promoting activity. The formulations as well as minoxidil (2%) solution (positive control) were applied topically on shaved skin of rats, and the time required for initiation and completion of hair growth cycle was recorded. Hair growth initiation time was markedly reduced to one third on treatment with the prepared formulation compared with control animals. The time required for complete hair growth was also reduced by 32%. Quantitative analysis of hair growth cycle after treatment with formulations and minoxidil (2%) exhibited greater number of hair follicles in anagenic phase compared with control. The results thus corroborate with the traditionally acclaimed hair growth-promoting capabilities of the plants. The prepared formulation also holds potential for treatment of alopecia.

The M4 muscarinic acetylcholine receptor plays a key role in the control of murine hair follicle cycling and pigmentation

Cholinergic receptors of the muscarinic class (M1–M5) are expressed in epidermal keratinocytes and melanocytes as well as in the hair follicle. Knockout (KO) mice of all five receptors have been created and resulted in different phenotypes. KO mice with a deletion of the M4 muscarinic acetylcholine receptor (M4R) present a striking hair phenotype, which we have analyzed here in greater detail by quantitative histomorphometry. Earlier studies revealed a retarded hair follicle morphogenesis in M4R KO mice, compared to age-matched wild type controls. On day 17, when mice enter the first hair growth cycle, the KO mice still showed a slightly retarded catagen phase. Subsequently, hair follicles of the KO mice stayed in a highly significantly prolonged telogen phase, while wild type mice had already far progressed in the hair cycle by entry into anagen. Most strikingly, the M4R KO mice did not engage in follicular melanogenesis and failed to produce pigmented hair shafts. The current pilot study suggests that the M4R plays a fundamental role in the control of the murine hair follicle cycling and is an essential signaling element in the control of hair follicle pigmentation.

Thyroid hormones in small ruminants: effects of endogenous, environmental and nutritional factors

Appropriate thyroid gland function and thyroid hormone activity are considered crucial to sustain the productive performance in domestic animals (growth, milk or hair fibre production). Changes of blood thyroid hormone concentrations are an indirect measure of the changes in thyroid gland activity and circulating thyroid hormones can be considered as indicators of the metabolic and nutritional status of the animals. Thyroid hormones play a pivotal role in the mechanisms permitting the animals to live and breed in the surrounding environment. Variations in hormone bioactivity allow the animals to adapt their metabolic balance to different environmental conditions, changes in nutrient requirements and availability, and to homeorhetic changes during different physiological stages. This is particularly important in the free-ranging and grazing animals, such as traditionally reared small ruminants, whose main physiological functions (feed intake, reproduction, hair growth) are markedly seasonal. Many investigations dealt with the involvement of thyroid hormones in the expression of endogenous seasonal rhythms, such as reproduction and hair growth cycles in fibre-producing (wool, mohair, cashmere) sheep and goats. Important knowledge about the pattern of thyroid hormone metabolism and their role in ontogenetic development has been obtained from studies in the ovine foetus and in the newborn. Many endogenous (breed, age, gender, physiological state) and environmental factors (climate, season, with a primary role of nutrition) are able to affect thyroid activity and hormone concentrations in blood, acting at the level of hypothalamus, pituitary and/or thyroid gland, as well as on peripheral monodeiodination. Knowledge on such topics mirror physiological changes and possibly allows the monitoring and manipulation of thyroid physiology, in order to improve animal health, welfare and production.

Effect of Citrullus colocynthis. on Hair Growth in Albino Rats

Citrullus colocynthis. Schrad (Cucurbitaceae) is a traditionally acclaimed hair tonic in Ayurveda (the traditional Indian system of medicine). Studies were therefore undertaken to evaluate petroleum ether and ethanol extracts of C. colocynthis. for their effect on hair growth in albino rats. The extracts incorporated into oleaginous ointment base were applied topically on shaved denuded skin of albino rats. The time required for initiation of hair growth as well as completion of hair growth cycle was recorded. Minoxidil 2% solution was applied topically and served as the standard. Hair growth initiation time was significantly reduced to half on treatment with the petroleum ether extracts compared with untreated control animals. The time required for complete hair growth was also considerably reduced. The treatment was successful in bringing a greater number of hair follicles (>70%) to anagenic phase than standard minoxidil (67%). The result of treatment with 2 and 5% petroleum ether extracts were comparable with the standard minoxidil.

Paradoxical effects of hair removal systems: a review

Although a variety of lasers have proven to be clinically effective for long-term hair removal, the use of these lasers has also been associated with undesirable side effects, such as hyper- and hypopigmentation, crusting, erythema, and edema. One notable side effect that seems to be underreported in the literature is the growth of fine dark hair in untreated areas close to the treated ones. This contradictory hypertrichosis is known as the paradoxical effect. In this paper, we review the published reports of the paradoxical effect and offer some possible explanations for this effect. The paradoxical effect has been documented most commonly after the use of induced pulse light and alexandrite lasers. One possible explanation is the activation of dormant hair follicles by suboptimal fluences. Another mechanism may be the synchronization of hair growth cycles by direct light stimulation.

Prolactin delays hair regrowth in mice

Mammalian hair growth is cyclic, with hair-producing follicles alternating between active (anagen) and quiescent (telogen) phases. The timing of hair cycles is advanced in prolactin receptor (PRLR) knockout mice, suggesting that prolactin has a role in regulating follicle cycling. In this study, the relationship between profiles of circulating prolactin and the first post-natal hair growth cycle was examined in female Balb/c mice. Prolactin was found to increase at 3 weeks of age, prior to the onset of anagen 1 week later. Expression of PRLR mRNA in skin increased fourfold during early anagen. This was followed by upregulation of prolactin mRNA, also expressed in the skin. Pharmacological suppression of pituitary prolactin advanced dorsal hair growth by 3.5 days. Normal hair cycling was restored by replacement with exogenous prolactin for 3 days. Increasing the duration of prolactin treatment further retarded entry into anagen. However, prolactin treatments, which began after follicles had entered anagen at 26 days of age, did not alter the subsequent progression of the hair cycle. Skin from PRLR-deficient mice grafted onto endocrine-normal hosts underwent more rapid hair cycling than comparable wild-type grafts, with reduced duration of the telogen phase. These experiments demonstrate that prolactin regulates the timing of hair growth cycles in mice via a direct effect on the skin, rather than solely via the modulation of other endocrine factors.

Jagged 1 is a β-catenin target gene required for ectopic hair follicle formation in adult epidermis

The Wnt and Notch signalling pathways regulate hair follicle maintenance, but how they intersect is unknown. We show that Notch signalling is active in the hair follicle pre-cortex, a region of high Wnt activity, where commitment to hair lineages occurs. Deletion of jagged 1 (Jag1) results in inhibition of the hair growth cycle and conversion of hair follicles into cysts of cells undergoing interfollicular epidermal differentiation. Conversely, activation of Notch in adult epidermis triggers expansion of the base of the hair follicle, sebaceous gland enlargement and abnormal clumping of the follicles. In adult epidermis, the induction of new hair follicle formation by beta-catenin is prevented by blocking Notch signalling pharmacologically or through Jag1 deletion. Conversely, activation of both pathways accelerates growth and differentiation of ectopic follicles. beta-catenin stimulates Notch signalling by inducing Jag1 transcription. We conclude that the Notch pathway acts downstream of the Wnt/beta-catenin pathway to determine epidermal cell fate.

Protection Against Chemotherapy-Induced Alopecia

The goal is to provide an overview on the advances in protection against chemotherapy-induced alopecia (CIA). The four major parts of this review are (a) overview of the hair follicle biology, (b) characteristics of CIA, (c) state-of-the-art animal models of CIA, and (d) experimental approaches on protection against CIA. The hair follicle represents an unintended target of cancer chemotherapy. CIA is a significant side effect that compromises the quality of life of patients. Overcoming CIA represents an area of unmet needs, especially for females and children. Significant progresses have been made in the last decade on the pathobiology of CIA. The pharmacological agents under evaluation include drug-specific antibodies, hair growth cycle modifiers, cytokines and growth factors, antioxidants, cell cycle or proliferation modifiers, and inhibitors of apoptosis. Their potential applications and limitations are discussed. Multiple classes of agents with different action mechanisms have been evaluated in animal CIA models. Most of these protective agents have activity limited to a single chemotherapeutic agent. In comparison, calcitriol and cyclosporine A have broader spectrum of activity and can prevent against CIA by multiple chemotherapeutic agents. Among the three agents that have been evaluated in humans, AS101 and Minoxidil were able to reduce the severity or shorten the duration of CIA but could not prevent CIA.

Hormone‐related hair disorders – from clinical needs to new therapeutic perspectives

The hair follicle and its appendages are important target structures for hormones. Plasma levels, local hormone metabolism and differential receptor expression regulate hair growth and hair cycling as well as sebaceous gland function. Even minor imbalances in this system, e.g. abnormal expression of hair follicle‐associated isoenzymes, may cause clinical symptoms such as hair loss, seborrhoea or hirsutism.Conventional therapeutic strategies, which aim to control peripheral hyperandrogenism, include systemic administration of androgen inhibitors (e.g. oral contraceptives, GnRH analogues), peripheral androgen blockers (CPA, CMA, glutamide, finasteride) as well as topical application of estrogens. As our knowledge about hormone systems and their complex interactions increases, new molecules are gaining importance: rosiglitazone and metformin are compounds which increase the sensitivity to insulin, topical application of minoxidil has been shown to regulate perifollicular blood flow and vascularization, and anti‐inflammatory compounds can as well be beneficial in the treatment of androgenetic alopecia.Because such therapies are, still, rather unspecific, current research focuses on the development of individualized strategies which allow to specifically treat the various manifestations caused by hormone‐related disorders. From our perspective, the aims of future drug development are as follows.In the first place, the identification of new targets, possibly beyond sex steroids in the narrow sense is highly important. Components of the POMC‐system, for example, have been shown to regulate cell differentiation and also hair cycling.And secondly, to develop drug delivery systems, which allow to specifically directing active compounds to target structures. Such improved drug delivery may allow to reduce side‐effects and to increase the efficacy of current therapies. Studies by our group and others suggest that microparticles, due to their ability to aggregate in the hair follicle openings, are promising drug delivery systems. In fact, we recently reported that the penetration depths of transcutaneously applied microparticles into the follicular duct depends on the size of the particles and on the dimension of the hair follicle, suggesting that particle‐based drug delivery systems allow to selectively target hair follicle compartments such as the entry level of the sebaceous duct or the bulge region.

The genetically programmed hair growth cycle and alopecia: what is there to know?

Although commonly dismissed as being of superficial importance, the hair follicle is one of human biology’s most fascinating structures. One should not diminish the role of hair as a social and sexual communication signal in humans, as evidenced by the significant psychological trauma associated with its absence from the human scalp. Along with skin pigmentation, the hair fiber contributes much to the phenotypic variation between different human populations and can be significantly altered in its appearance. The last 20 years have seen a vast change in research activity into the regulation of hair growth in health and disease and, over the next 5 years, this should include further important glimpses of the nature of the hair follicle’s clock machinery (e.g., identification of the stop/start signals and triggers). Therapeutic and cosmetic manipulation of this mini organ will require a careful balance between delivery to the follicle of stimuli that are as specific as possible, while leaving other systems a...

PDGF isoforms induce and maintain anagen phase of murine hair follicles

It is known that platelet-derived growth factor (PDGF) receptors are expressed in hair follicle (HF) epithelium. The aim of the present study was to clarify the effects of PDGF-AA and -BB on the cyclic growth of HFs. PDGF-AA or -BB was injected into the dorsal skin of C3H mice during the second telogen phase once daily for five consecutive days, or PDGF-AA or -BB dissolved in hyaluronic acid was injected only once. In order to confirm the effects of different PDGF isoforms, anti-PDGF-AA antibody or anti-PDGF-BB antibody was injected just after each injection of PDGF-AA or -BB. In addition, anti-PDGF antibodies were injected into the skin of C3H mice during the second anagen phase once daily for 5 days. We studied expression of signaling molecules in the skin where anagen phase had been induced by PDGF injection by real-time RT-PCR. Both PDGF-AA and -BB injection experiments immediately induced the anagen phase of the hair growth cycle at the injection sites. The induction of anagen was interfered by anti-PDGF antibody treatment. Real-time RT-PCR using extracted RNA from the PDGF injected sites of skin samples showed upregulated expression of HF differentiation-related key signaling molecules, Sonic hedgehog (Shh), Lef-1 and Wnt5a. These results indicate that both PDGF-AA and -BB are involved in the induction and maintenance of the anagen phase in the mouse hair cycle. Local application of PDGF-AA and -BB might therefore prove to be an effective treatment option for alopecia associated with early catagen induction and elongated telogen phase.

Hair Growth Induced by Diode Laser Treatment

Although hair reduction by long-pulsed red and infrared lasers and light sources is generally quite effective, paradoxical hair growth has rarely been observed following treatment. To report a case of thick hair growth following 810 nm diode laser treatment and its subsequent treatment. METHODS. A 24-year-old man who had previously had laser hair reduction on his posterior neck was treated to a test area on his upper back. Thick terminal hair developed in the treated area subsequent to laser treatment. Further treatment of this area removed the terminal hair but resulted in terminal hair growth in an annular distribution surrounding the treatment site. Diode laser treatment rarely stimulates terminal hair growth. This phenomenon should be studied to better understand hair growth cycles and to help develop more effective treatments for hair loss and hair growth.

Identification of hair cycle-associated genes from time-course gene expression profile using fractal analysis

Microarray technology permits one to monitor thousands of processes going on inside the cell. This tool has been used to study gene expression profiles associated with the hair-growth cycle. We provide a novel method called the fractal analysis method to identify hair-growth cycle associated genes from time course gene expression profiles. Fractal analysis is a much better method than the computational method used by Lin et al. (2004). The fractal dimension obtained by fractal analysis process also indicates the irregularity in hair-growth pattern. The computational method used by Lin et al. (2004) was unable to make any inference about the hair-growth pattern.

Role of Androgen in Mesenchymal Epithelial Interactions in Human Hair Follicle

Human hair follicles, which are distributed in various and specific sites of the body, appear to have an inherited susceptibility for androgen-dependent growth. Beard, axillary, and frontal scalp dermal papilla cells (DPC) were recently shown to possess the characteristics of androgen target cells. These DPC show strong expression of androgen receptors, and the expression of type II 5alpha reductase is restricted to beard and frontal scalp DPC. These findings suggest that DPC mediate the signals of androgen to follicular epithelial cells in a paracrine fashion. We developed an in vitro co-culture system using DPC and keratinocytes (KC) to characterize the mode of androgen action in human hair follicles. Androgen significantly stimulated the proliferation of KC co-cultured with beard DPC, indicating that beard DPC produce androgen-dependent diffusible growth factors. Insulin-like growth factor-I was identified as one of the androgen-dependent paracrine growth factors produced by beard DPC. We also identified the inhibitory role of androgen on the growth of KC co-cultured with DPC from androgenetic alopecia (AGA) when the DPC were transfected with an expression vector encoding the androgen receptor. This growth suppression of KC was mediated by transforming growth factor-beta1 (TGF-beta1) derived from DPC of AGA, suggesting that TGF-beta1 is a paracrine mediator for AGA.

Epilation Today: Physiology of the Hair Follicle and Clinical Photo-Epilation

Despite the variations of length and type of hair (vellus or terminal), the growth of human hair in all body sites is cyclic. Phases of active hair growth, or anagen, are separated by periods of quiescence, or telogen. The duration of both phases varies greatly depending on the body site. Whether hairs are in anagen/telogen at the time of hair removal is important because only anagen hairs are particularly sensible to physical insults. Photo-epilation is a technique for long-term removal of unwanted hair by thermal destruction of the hair follicle and its reproductive system (stems cells). As melanin is the main chromophor existing in hair follicles the corresponding wavelength spectrum would range from ultraviolet up to infrared light. Furthermore longer wavelengths are preferred as the cromophor lies deep in the skin and the penetration of light is increasing with the wavelength. Thus, in the range of 600-1100 nm melanin absorption may be used for selective photothermolysis of hair follicles. Yet to be resolved questions for permanent destruction are the location of the key follicular target and the possible influence of the hair growth cycle on photothermolysis-induced hair removal. An overview on the individual physiology of the hair follicle is given to discuss the latest strategies for photo-epilation.