Medicine › Urology

Regulation and Function of Hair Follicle Stem Cells

Description

This cluster of papers focuses on the regulation and function of hair follicle stem cells, including their role in skin development, regeneration, and the maintenance of the epidermal niche. It explores the signaling pathways such as Wnt signaling, the contribution of bulge cells, and the interactions between epithelial and mesenchymal cells. Additionally, it delves into the implications for conditions like alopecia areata.

Keywords

Hair Follicle; Stem Cells; Epidermal Niche; Wnt Signaling; Skin Development; Regeneration; Bulge Cells; Cycling; Epithelial-Mesenchymal Interactions; Alopecia Areata

The need for a widely accepted, accurate, and reproducible standard of classification for male pattern baldness has increased with the advent and increasing popularity of hair transplant surgery. This report … The need for a widely accepted, accurate, and reproducible standard of classification for male pattern baldness has increased with the advent and increasing popularity of hair transplant surgery. This report establishes such a classification, and reports its use in determining the incidence of male pattern baldness at various ages in 1,000 white adult male subjects. The action of testosterone as an incitant in male pattern baldness is well known, but this study points out the continued effect of time, even in later years. Since most hair transplant surgery is peformed on subjects with male pattern baldness, and because the success of hair transplant surgery is largely dependent on proper patient selection, a complete understanding of male pattern baldness is essential for consistently good results with hair transplantation.
Androgenetic alopecia in the female occurs much more frequently than is generally believed. The condition is still considered infrequent, for it differs, in its clinical picture and in the sequence … Androgenetic alopecia in the female occurs much more frequently than is generally believed. The condition is still considered infrequent, for it differs, in its clinical picture and in the sequence of events leading to it, from common baldness in men. To facilitate an early diagnosis (desirable in view of the therapeutic possibilities by means of antiandrogens) a classification of the stages of the common form (female type) of androgenetic alopecia in women is presented. The exceptionally observed male type of androgenetic alopecia can be classified according to Hamilton or to the modification of this classification proposed by Ebling & Rook.
Mammalian epidermis consists of three self-renewing compartments: the hair follicle, the sebaceous gland, and the interfollicular epidermis. We generated knock-in alleles of murine Lgr6, a close relative of the Lgr5 … Mammalian epidermis consists of three self-renewing compartments: the hair follicle, the sebaceous gland, and the interfollicular epidermis. We generated knock-in alleles of murine Lgr6, a close relative of the Lgr5 stem cell gene. Lgr6 was expressed in the earliest embryonic hair placodes. In adult hair follicles, Lgr6+ cells resided in a previously uncharacterized region directly above the follicle bulge. They expressed none of the known bulge stem cell markers. Prenatal Lgr6+ cells established the hair follicle, sebaceous gland, and interfollicular epidermis. Postnatally, Lgr6+ cells generated sebaceous gland and interfollicular epidermis, whereas contribution to hair lineages gradually diminished with age. Adult Lgr6+ cells executed long-term wound repair, including the formation of new hair follicles. We conclude that Lgr6 marks the most primitive epidermal stem cell.
The murine hair follicle undergoes pronounced cyclic expansion and regression, leading to rapidly changing demands for its vascular support. Our study aimed to quantify the cyclic changes of perifollicular vascularization … The murine hair follicle undergoes pronounced cyclic expansion and regression, leading to rapidly changing demands for its vascular support. Our study aimed to quantify the cyclic changes of perifollicular vascularization and to characterize the biological role of VEGF for hair growth, angiogenesis, and follicle cycling. We found a significant increase in perifollicular vascularization during the growth phase (anagen) of the hair cycle, followed by regression of angiogenic blood vessels during the involution (catagen) and the resting (telogen) phase. Perifollicular angiogenesis was temporally and spatially correlated with upregulation of VEGF mRNA expression by follicular keratinocytes of the outer root sheath, but not by dermal papilla cells. Transgenic overexpression of VEGF in outer root sheath keratinocytes of hair follicles strongly induced perifollicular vascularization, resulting in accelerated hair regrowth after depilation and in increased size of hair follicles and hair shafts. Conversely, systemic treatment with a neutralizing anti-VEGF antibody led to hair growth retardation and reduced hair follicle size. No effects of VEGF treatment or VEGF blockade were observed in mouse vibrissa organ cultures, which lack a functional vascular system. These results identify VEGF as a major mediator of hair follicle growth and cycling and provide the first direct evidence that improved follicle vascularization promotes hair growth and increases hair follicle and hair size.
Mathematical reaction-diffusion models have been suggested to describe formation of animal pigmentation patterns and distribution of epidermal appendages. However, the crucial signals and in vivo mechanisms are still elusive. Here … Mathematical reaction-diffusion models have been suggested to describe formation of animal pigmentation patterns and distribution of epidermal appendages. However, the crucial signals and in vivo mechanisms are still elusive. Here we identify WNT and its inhibitor DKK as primary determinants of murine hair follicle spacing, using a combined experimental and computational modeling approach. Transgenic DKK overexpression reduces overall appendage density. Moderate suppression of endogenous WNT signaling forces follicles to form clusters during an otherwise normal morphogenetic program. These results confirm predictions of a WNT/DKK-specific mathematical model and provide in vivo corroboration of the reaction-diffusion mechanism for epidermal appendage formation.
Abstract LEF/TCF DNA-binding proteins act in concert with activated β-catenin, the product of Wnt signaling, to transactivate downstream target genes. To probe the role of activated LEF/TCF transcription factor complexes … Abstract LEF/TCF DNA-binding proteins act in concert with activated β-catenin, the product of Wnt signaling, to transactivate downstream target genes. To probe the role of activated LEF/TCF transcription factor complexes in hair follicle morphogenesis and differentiation, we engineered mice harboring TOPGAL, a β-galactosidase gene under the control of a LEF/TCF and β-catenin inducible promoter. In mice, TOPGAL expression was directly stimulated by a stabilized form of β-catenin, but was also dependent upon LEF1/TCF3 in skin. During embryogenesis, TOPGAL activation occurred transiently in a subset of LEF1-positive cells of pluripotent ectoderm and underlying mesenchyme. Downgrowth of initiated follicles proceeded in the absence of detectable TOPGAL expression, even though LEF1 was still expressed. While proliferative matrix cells expressed the highest levels of Lef1 mRNAs, LEF1 concentrated in the precursor cells to the hair shaft, where TOPGAL expression was co-induced with hair-specific keratin genes containing LEF/TCF-binding motifs. LEF1 and TOPGAL expression ceased during catagen and telogen, but reappeared at the start of the postnatal hair cycle, concomitant with precortex formation. In contrast to hair shaft precursor cells, postnatal outer root sheath expressed TCF3, but not TOPGAL. TCF3 was also expressed in the putative follicle stem cells, and while TOPGAL was generally silent in this compartment, it was stimulated at the start of the hair cycle in a fashion that appeared to be dependent upon stabilization of β-catenin. Taken together, our findings demonstrate that LEF1/TCF3 is necessary but not sufficient for TOPGAL activation, revealing the existence of positive and negative regulators of these factors in the skin. Furthermore, our findings unveil the importance of activated LEF/TCF complexes at distinct times in hair development and cycling when changes in cell fate and differentiation commitments take place.
Nearly 50 years ago, Chase published a review of hair cycling in which he detailed hair growth in the mouse and integrated hair biology with the biology of his day. … Nearly 50 years ago, Chase published a review of hair cycling in which he detailed hair growth in the mouse and integrated hair biology with the biology of his day. In this review we have used Chase as our model and tried to put the adult hair follicle growth cycle in perspective. We have tried to sketch the adult hair follicle cycle, as we know it today and what needs to be known. Above all, we hope that this work will serve as an introduction to basic biologists who are looking for a defined biological system that illustrates many of the challenges of modern biology: cell differentiation, epithelial-mesenchymal interactions, stem cell biology, pattern formation, apoptosis, cell and organ growth cycles, and pigmentation. The most important theme in studying the cycling hair follicle is that the follicle is a regenerating system. By traversing the phases of the cycle (growth, regression, resting, shedding, then growth again), the follicle demonstrates the unusual ability to completely regenerate itself. The basis for this regeneration rests in the unique follicular epithelial and mesenchymal components and their interactions. Recently, some of the molecular signals making up these interactions have been defined. They involve gene families also found in other regenerating systems such as fibroblast growth factor, transforming growth factor-β, Wnt pathway, Sonic hedgehog, neurotrophins, and homeobox. For the immediate future, our challenge is to define the molecular basis for hair follicle growth control, to regenerate a mature hair follicle in vitro from defined populations, and to offer real solutions to our patients' problems.
The human hair follicle bulge is an important niche for keratinocyte stem cells (KSCs). Elucidation of human bulge cell biology could be facilitated by analysis of global gene expression profiles … The human hair follicle bulge is an important niche for keratinocyte stem cells (KSCs). Elucidation of human bulge cell biology could be facilitated by analysis of global gene expression profiles and identification of unique cell-surface markers. The lack of distinctive bulge morphology in human hair follicles has hampered studies of bulge cells and KSCs. In this study, we determined the distribution of label-retaining cells to define the human anagen bulge. Using navigated laser capture microdissection, bulge cells and outer root sheath cells from other follicle regions were obtained and analyzed with cDNA microarrays. Gene transcripts encoding inhibitors of WNT and activin/bone morphogenic protein signaling were overrepresented in the bulge, while genes responsible for cell proliferation were underrepresented, consistent with the existence of quiescent noncycling KSCs in anagen follicles. Positive markers for bulge cells included CD200, PHLDA1, follistatin, and frizzled homolog 1, while CD24, CD34, CD71, and CD146 were preferentially expressed by non-bulge keratinocytes. Importantly, CD200+ cells (CD200hiCD24loCD34loCD71loCD146lo) obtained from hair follicle suspensions demonstrated high colony-forming efficiency in clonogenic assays, indicating successful enrichment of living human bulge stem cells. The stem cell behavior of enriched bulge cells and their utility for gene therapy and hair regeneration will need to be assessed in in vivo assays.
We have known for over 30 years that minoxidil stimulates hair growth, yet our understanding of its mechanism of action on the hair follicle is very limited. In animal studies, … We have known for over 30 years that minoxidil stimulates hair growth, yet our understanding of its mechanism of action on the hair follicle is very limited. In animal studies, topical minoxidil shortens telogen, causing premature entry of resting hair follicles into anagen, and it probably has a similar action in humans. Minoxidil may also cause prolongation of anagen and increases hair follicle size. Orally administered minoxidil lowers blood pressure by relaxing vascular smooth muscle through the action of its sulphated metabolite, minoxidil sulphate, as an opener of sarcolemmal KATP channels. There is some evidence that the stimulatory effect of minoxidil on hair growth is also due to the opening of potassium channels by minoxidil sulphate, but this idea has been difficult to prove and to date there has been no clear demonstration that KATP channels are expressed in the hair follicle. A number of in vitro effects of minoxidil have been described in monocultures of various skin and hair follicle cell types including stimulation of cell proliferation, inhibition of collagen synthesis, and stimulation of vascular endothelial growth factor and prostaglandin synthesis. Some or all of these effects may be relevant to hair growth, but the application of results obtained in cell culture studies to the complex biology of the hair follicle is uncertain. In this article we review the current state of knowledge on the mode of action of minoxidil on hair growth and indicate lines of future research.
In the (Stem Cell) Zone Efforts to isolate and characterize various types of stem cells have revealed much about the molecular mechanisms of stem cell self-renewal and differentiation, as well … In the (Stem Cell) Zone Efforts to isolate and characterize various types of stem cells have revealed much about the molecular mechanisms of stem cell self-renewal and differentiation, as well as the function of the microenvironment, or stem cell niche. Li and Clevers (p. 542 ) review what is known about stem cells in the hair follicle, bone marrow, and intestinal epithelium and suggest that two stem cell populations, one that is quiescent and one that is actively in the cell cycle, may coexist in these tissues in a so-called ā€œzonedā€ stem cell model.
Many adult regenerative cells divide infrequently but have high proliferative capacity. We developed a strategy to fluorescently label slow-cycling cells in a cell type-specific fashion. We used this method to … Many adult regenerative cells divide infrequently but have high proliferative capacity. We developed a strategy to fluorescently label slow-cycling cells in a cell type-specific fashion. We used this method to purify the label-retaining cells (LRCs) that mark the skin stem cell (SC) niche. We found that these cells rarely divide within their niche but change properties abruptly when stimulated to exit. We determined their transcriptional profile, which, when compared to progeny and other SCs, defines the niche. Many of the >100 messenger RNAs preferentially expressed in the niche encode surface receptors and secreted proteins, enabling LRCs to signal and respond to their environment.
The skin constantly renews itself throughout adult life, and the hair follicle undergoes a perpetual cycle of growth and degeneration. Stem cells (SCs) residing in the epidermis and hair follicle … The skin constantly renews itself throughout adult life, and the hair follicle undergoes a perpetual cycle of growth and degeneration. Stem cells (SCs) residing in the epidermis and hair follicle ensure the maintenance of adult skin homeostasis and hair regeneration, but they also participate in the repair of the epidermis after injuries. We summarize here the current knowledge of epidermal SCs of the adult skin. We discuss their fundamental characteristics, the methods recently designed to isolate these cells, the genes preferentially expressed in the multipotent SC niche, and the signaling pathways involved in SC niche formation, SC maintenance, and activation. Finally, we speculate on how the deregulation of these pathways may lead to cancer formation.
Hair has many useful biologic functions, including protection from the elements and dispersion of sweat-gland products (e.g., pheromones). It also has psychosocial importance in our society, and patients with hair … Hair has many useful biologic functions, including protection from the elements and dispersion of sweat-gland products (e.g., pheromones). It also has psychosocial importance in our society, and patients with hair loss (alopecia) (Table 1) or excessive hair growth often suffer tremendously. Not surprisingly, the demand for drugs that alter hair growth and appearance has led to a multibillion-dollar industry, yet few drugs that are effective for these purposes are available. However, recent progress in our understanding of the biology and pathology of hair follicles should lead to more effective therapies for disorders of hair growth.Structure and Function of Hair . . .
Scientific Reports 6: Article number: 26436; published online: 23 May 2016; updated: 14 November 2016 The original version of this Article contained errors in the affiliations. ā€œDepartment of Cell Biology … Scientific Reports 6: Article number: 26436; published online: 23 May 2016; updated: 14 November 2016 The original version of this Article contained errors in the affiliations. ā€œDepartment of Cell Biology and Anatomy, National Cheng Kung University, Tainan, 701, Taiwanā€ was incomplete, and now reads:
BACKGROUND Male and female pattern hair loss (MPHL and FPHL) significantly affect quality of life. This study compares the clinical and trichoscopic outcomes of platelet-rich plasma (PRP) and growth factor … BACKGROUND Male and female pattern hair loss (MPHL and FPHL) significantly affect quality of life. This study compares the clinical and trichoscopic outcomes of platelet-rich plasma (PRP) and growth factor concentrate (GFC) in treating patterned hair loss, evaluating their efficacy and safety. OBJECTIVE To compare the efficacy and side effect profiles of PRP and GFC in treating pattern hair loss and assessing associated trichoscopic changes. METHODS A retrospective study of 42 patients (21 MPHL and 21 FPHL), divided into Group 1 (PRP, 25 patients) and Group 2 (GFC, 17 patients). Each underwent three treatment sessions, 4 weeks apart. Evaluations included trichoscopy, clinical photography, and the Global Aesthetic Improvement Scale (GAIS). RESULTS GFC showed better outcomes in total hair count, shaft diameter, and GAIS score than PRP, with significant improvement in hair count after the second session ( p < .05). GFC also had more bulbar enlargement ( p < .05), while PRP showed more erythema and angiogenesis ( p < .05). At 6 months, PRP had better hair diameter and GAIS scores, indicating a more sustained effect. CONCLUSION PRP and GFC improve hair parameters with choices based on patient preference, cost, and expertise. GFC provides quick improvement, while PRP offers long-term benefits, making sequential treatments ideal for sustainable results.
Hair follicles regenerate spontaneously through a cycle of anagen, catagen, and telogen, and this cycle is driven by hair follicle stem cells (HFSCs). Long non-coding RNAs (lncRNAs) have previously been … Hair follicles regenerate spontaneously through a cycle of anagen, catagen, and telogen, and this cycle is driven by hair follicle stem cells (HFSCs). Long non-coding RNAs (lncRNAs) have previously been implicated in hair follicle cycling processes. According to the previous lncRNA sequencing results of cashmere goats, an annotated lncRNA XR_310056.1, referred to as lnc056, was found to be differentially expressed during the hair follicle cycle. Here, the purpose of this study was to determine whether lnc056 affects the proliferation of HFSCs by regulating thyroid hormone receptor interactor 6 (TRIP6) expression in combination with the transcription factor HNRNPUL1. The expression of lnc056 in HFSCs was detected by RT-qPCR. HFSCs were then treated with lnc056 and TRIP6 overexpressing adenovirus, si-HNRNPUL1, and si-TRIP6 to detect cell viability and proliferation. In addition, we investigated the binding between lnc056 and HNRNPUL1 or HNRNPUL1 and TRIP6. Finally, the biological function of lnc056 through the HNRNPUL1/TRIP6 axis was verified by target gene recovery experiments. Lnc056 was expressed in the nuclei of HFSCs, and its overexpression promoted the proliferation of cells. Moreover, lnc056 was found to bind to the transcription factor HNRNPUL1 and promoted TRIP6 expression. Furthermore, recovery assays demonstrated that lnc056 promoted the proliferation of HFSCs via the HNRNPUL1/TRIP6 axis. In summary, the results of this study suggested that lnc056 up-regulated the expression of TRIP6 by binding to the transcription factor HNRNPUL1, thereby accelerating the proliferation of HFSCs. This study enriches the molecular mechanism of lncRNA in the hair follicle cycle and provides a potential therapeutic target for hair loss.
Androgenetic alopecia is the most common type of hair loss in men. It is reported to have a strong effect on the quality of life, especially at a young age. … Androgenetic alopecia is the most common type of hair loss in men. It is reported to have a strong effect on the quality of life, especially at a young age. However, there are only a few studies evaluating the relationship between androgenetic alopecia and psychosocial well-being in the general population. This study examined the association of androgenetic alopecia and its severity with psychosocial symptoms and sexual issues at a population level in male subjects aged between 33 and 35 years belonging to the Northern Finland Birth Cohort 1986 Study (NFBC1986) (n = 1,027). During 2019 to 2020, cohort subjects participated in a large follow-up study and completed diverse health questionnaires, including information on their hair status, psychosocial symptoms (the Hopkins Symptom Checklist-25 [HSCL-25] and the Generalized Anxiety Disorder Screener [GAD-7]) and sexual health. Androgenetic alopecia was reported as follows: No androgenetic alopecia n = 468 (45.6%), mild n = 435 (42.4%), moderate n = 62 (6.0%), and severe androgenetic alopecia n = 62 men (6.0%). There was no significant association of androgenetic alopecia presence or its severity with depression, anxiety, or sexual symptoms. In conclusion, contrary to previous findings, a relationship between androgenetic alopecia and psychosocial problems in early midlife was not found.
Alopecia areata (AA) is a common form of non-scarring hair loss of scalp and/or body. Genetic predisposition, autoimmunity, and environmental factors play a major role in the etiopathogenesis of AA. … Alopecia areata (AA) is a common form of non-scarring hair loss of scalp and/or body. Genetic predisposition, autoimmunity, and environmental factors play a major role in the etiopathogenesis of AA. Patchy AA is the most common form, with an incidence of around 0.7% in northern India. Conventional treatments like corticosteroids often result in unwanted side effects such as skin thinning, skin atrophy etc, prompting exploration of alternative therapies. This case study presents the successful management of AA using Ayurvedic approach that includes Kuttana Karma(~microneedling with a 1 mm Derma-roller) and Shirolepa (~herbal paste application), along with internal Ayurvedic medications. A 22-year-old woman with patchy hair loss and a SALT score of 22% sought treatment after seeing no results with earlier therapies. She underwent a one-month treatment plan involving weekly Derma-roller sessions, daily application of Rakta Gunja beeja choorna lepa (10gm) and oral intake of Rasayana choorna (6gm)Over the course of treatment, she experienced steady improvement in hair growth. By the final visit, the SALT score decreased to 0%. The combination of microneedling and Ayurvedic therapies helped to improve scalp blood circulation, nutrient absorption addressing the disease root cause. This case report suggests the effectiveness of Ayurvedic management in treating Indralupta (~AA).
Hair loss is a common condition that can negatively impact an individual’s psychological well-being and overall quality of life. Recent studies have shown that secondary metabolites derived from herbal plants … Hair loss is a common condition that can negatively impact an individual’s psychological well-being and overall quality of life. Recent studies have shown that secondary metabolites derived from herbal plants possess potential as natural agents to stimulate hair growth. This review aims to provide a scientific basis for the development of herbal-based hair growth formulations in the future. The literature reviewed was sourced from major scientific databases such as PubMed, Scopus, ScienceDirect, and Google Scholar, with a focus on publications from the last ten years. This review discusses various groups of bioactive compounds including flavonoids, alkaloids, phenolics, polyphenols, phenylpropanoids, and saponins that play a role in follicle regeneration and alopecia prevention. The pharmacological effects of these compounds occur through several mechanisms, such as prolonging the anagen phase of the hair cycle, inhibiting the enzyme 5-α-reductase, enhancing blood circulation via vasodilation, and exhibiting strong antioxidant and anti-inflammatory activities. Findings from in vitro and in vivo studies indicate that these natural compounds show promise in promoting hair growth, although further clinical trials are needed to confirm their efficacy.
ABSTRACT Baricitinib, a Janus kinase inhibitor, demonstrated efficacy in achieving scalp hair regrowth in severe alopecia areata (AA). While short‐term real‐world data on its efficacy have been reported, long‐term data … ABSTRACT Baricitinib, a Janus kinase inhibitor, demonstrated efficacy in achieving scalp hair regrowth in severe alopecia areata (AA). While short‐term real‐world data on its efficacy have been reported, long‐term data remain limited. This retrospective observational study spanning 104 weeks analyzed clinical trajectories of 51 severe AA patients treated with baricitinib. Among them, 36 continued treatment for 104 weeks, with 55.6% achieving a SALT score of ≤ 20 and 72.2% achieving ≄ 30% improvement from baseline in SALT score (SALT 30 ). Multivariate analysis identified female sex and disease duration < 4 years as significant predictors of response. Furthermore, patients with eyebrow or eyelash regrowth at 52 weeks had a higher likelihood of achieving long‐term scalp hair regrowth. We identified a subgroup of markedly slow responders who achieved SALT 30 between 52 and 104 weeks, many of whom had eyebrow or eyelash regrowth at 52 weeks. Baricitinib was well tolerated throughout the study period, with no serious long‐term adverse effects. Our findings supported baricitinib's long‐term efficacy and safety and suggested predictive factors for treatment responses in severe AA.
Hair loss is a distressing problem that affects the self-image and quality of life of many people. The increasing demand for alternative treatments has led to growing interest in using … Hair loss is a distressing problem that affects the self-image and quality of life of many people. The increasing demand for alternative treatments has led to growing interest in using herbal medicine for hair loss management. This literature review is divided into two main parts: a narrative overview and a systematic synthesis, evaluating the efficacy of herbal remedies, gathering findings from recent clinical studies, and traditional practices. The narrative section explores the pathophysiology of hair loss, contributing factors, and conventional pharmacological treatments, including their limitations and adverse effects. The second part presents a systematic review of sixteen randomized controlled trials evaluating the clinical efficacy and safety of herbal remedies for hair loss. Natural products such as rosemary, green tea, ginseng, Aloe vera, olive, and saw palmetto have shown promising efficacy in promoting hair growth, improving hair density, reducing hair shedding, and enhancing patient satisfaction through mechanisms involving anti-inflammatory, hormonal, and enhanced scalp circulation. However, study design limitations and outcome variability necessitate further rigorous, standardized research. This review aims to offer an integrative, evidence-informed perspective on the therapeutic potential of herbal medicine for hair loss in clinical evidence.
Background Hair plays a crucial role in social and sexual communication; hair disorders such as alopecia or hirsutism can therefore cause psychological distress. Current treatments are limited by unwanted side … Background Hair plays a crucial role in social and sexual communication; hair disorders such as alopecia or hirsutism can therefore cause psychological distress. Current treatments are limited by unwanted side effects and a lack of understanding of hair follicle (HF) regulation, particularly in miniaturised intermediate or vellus-like follicles; the clinical targets in hair loss disorders. The discovery that bimatoprost, a prostamide F 2α analogue, stimulates eyelash growth suggest a possible role for other prostanoids in hair growth. Objectives To evaluate the impact of the naturally occurring prostaglandin F 2α (PGF 2α ) on human intermediate HF growth, comparing the effects on matched terminal and intermediate follicles using a pre-clinical ex vivo organ culture model. Furthermore, to determine the involvement of PGF 2α receptors (FP) and their location within both these HF types. Methods Matched human female pre-auricular facelift skin HFs were incubated with PGF 2α alone or in combination with an FP antagonist for 9 days in the gold-standard ex vivo HF organ culture model. To confirm FP gene expression in both terminal and intermediate lower HF bulbs, RT-PCR was performed using specific FP primers, confirmed by sequence analysis. Immunohistochemistry was conducted using frozen sections to locate the FP protein in HF components. Results PGF 2α (100 nM) stimulated terminal HF fibre growth by 4.93% (p = 0.019) with a greater effect (10.03% (p < 0.001) stimulation) on intermediate HFs. PGF 2α stimulation significantly prolonged anagen (the growth phase of the hair cycle) duration in both HF types and to similar extent. These increases in hair fibre elongation were blocked by the receptor (FP) antagonist in both terminal and intermediate follicles. RT-PCR confirmed FP gene expression and immunohistochemistry located FP protein in the dermal papilla and connective tissue sheath of both intermediate and terminal HFs. Conclusion We demonstrate, for the first time, that PGF 2α stimulates human HF growth in organ culture via a receptor-driven mechanism, probably directly affecting the follicles’ regulatory dermal papilla function. The greater response of intermediate, compared to matched terminal, HFs suggests potential future clinical significance for medical conditions such as alopecia, or insufficient beard growth, and promoting hair growth in ā€˜relatively hairless’ donor graft skin or transplant follicles after elective, trauma or burn injury surgical reconstruction.
Background/Objectives: Frontal fibrosing alopecia (FFA) is a scarring alopecia with an unclear aetiology, primarily affecting postmenopausal women. This study aims to identify potential risk factors contributing to FFA development and … Background/Objectives: Frontal fibrosing alopecia (FFA) is a scarring alopecia with an unclear aetiology, primarily affecting postmenopausal women. This study aims to identify potential risk factors contributing to FFA development and progression, as well as provide a clinical profile to aid in the differential diagnosis. Methods: The study included 19 women diagnosed with FFA. The participants completed a 20-question survey based on a literature review of potential risk factors. Statistical analyses were performed to investigate the associations between patient characteristics and FFA. Results: All patients were female and their mean age was 60.58 years (SD = 12.81). In 63.1% of the cases, FFA onset occurred postmenopause, with a mean latency of 8.17 years. In the majority of cases, the diagnostic delay exceeded five years. The average menarche age was 13.68 years (SD = 2.06), whereas late menarche (≄15 years) was found in two subjects. A history of reproductive organ or breast malignancy was reported by 42.1% of the patients, which frequently required surgery. Most subjects did not receive hormone replacement therapy, or hormonal contraception. The most prevalent comorbidity was hypothyroidism (89.47%). Although smoking was rare among the subjects, hair colouring was quite common, yet no participant underwent scalp aesthetic procedures. In 47.4% of cases, scalp itching or pain was present. Sunscreens were frequently used, mostly on a daily or seasonal basis. Conclusions: FFA predominantly affects women in their early 60s, often following the menopause. In our study, a tendency toward an early menopause and an above-average menarche age of the subjects was observed. In the analysed group, only reproductive and breast cancers were reported, which requires further investigation. Frequent β-blocker use, second only to levothyroxine, may suggest that they play a role in FFA pathogenesis. Itching and pain of the scalp may contribute to the correct diagnosis, although these symptoms are not universal. Moreover, sunscreens were indicated as a potential trigger, yet avoiding them should not be routinely recommended due to the risk of carcinogenesis. The variability in the diagnostic delay emphasises the need for increasing clinician awareness and conducting further research.
Hair luster, a key component of visual hair quality, depends largely on the integrity of the cuticle. While cosmetic products offer temporarily enhanced luster, their effects are limited due to … Hair luster, a key component of visual hair quality, depends largely on the integrity of the cuticle. While cosmetic products offer temporarily enhanced luster, their effects are limited due to a poor understanding of the underlying molecular mechanisms. In this study, we employed a UVB-induced mouse model of hair luster loss to identify differentially expressed genes via quantitative real-time reverse transcription PCR. Key candidate genes were subsequently validated in vitro using human hair follicle dermal papilla cells and in ex vivo human scalp hair follicle tissue models. Subsequently, we evaluated the effects of minoxidil, caffeine, and biotin on gene expression and luster restoration. UVB exposure suppressed several luster-related genes, with COL7A1 consistently downregulated across all models. Treatment with minoxidil, caffeine, and biotin restored the expression of COL7A1 along with KRTAP5-5, KRTAP5-4, TGM3, and PTK7. These findings highlight COL7A1 as a novel molecular marker for hair luster and support its modulation as a potential therapeutic strategy.
Melatonin, a neurohormone regulating circadian rhythms, also plays a role in hair follicle physiology through its antioxidant and anti-inflammatory effects. This scoping review aimed to assess preclinical and clinical evidence … Melatonin, a neurohormone regulating circadian rhythms, also plays a role in hair follicle physiology through its antioxidant and anti-inflammatory effects. This scoping review aimed to assess preclinical and clinical evidence supporting melatonin as a therapeutic option for alopecia. A systematic search of MEDLINE, Scopus, and DOAJ identified studies on androgenetic alopecia, telogen effluvium, and diffuse hair loss. Preclinical findings suggest melatonin promotes follicular stem cell proliferation, modulates signaling pathways, and protects against damage. Clinical trials indicate that topical melatonin increases hair density, prolongs the anagen phase, and reduces hair shedding with minimal adverse effects. While current evidence supports its potential, variability in study design highlights the need for standardized clinical trials.
Este estudo observacional analisou a influĆŖncia do tratamento da disbiose intestinal como estratĆ©gia complementar no manejo da alopecia androgenĆ©tica. Seis voluntĆ”rios participaram de um protocolo capilar padrĆ£o, sendo trĆŖs deles … Este estudo observacional analisou a influĆŖncia do tratamento da disbiose intestinal como estratĆ©gia complementar no manejo da alopecia androgenĆ©tica. Seis voluntĆ”rios participaram de um protocolo capilar padrĆ£o, sendo trĆŖs deles submetidos, adicionalmente, Ć  investigação clĆ­nica e Ć  modulação da microbiota intestinal. Os resultados demonstraram que os indivĆ­duos que trataram a disbiose apresentaram melhora clĆ­nica significativa em comparação Ć queles que realizaram apenas o protocolo capilar. A anĆ”lise descritiva reforƧa a importĆ¢ncia do eixo intestino pele na saĆŗde capilar e aponta para a necessidade de abordagens terapĆŖuticas integrativas.
Introduction . Diffuse alopecia accounts for up to 40 % of all alopecia cases, making it one of the most common reasons patients consult dermatologists and cosmetologists. The pathogenesis of … Introduction . Diffuse alopecia accounts for up to 40 % of all alopecia cases, making it one of the most common reasons patients consult dermatologists and cosmetologists. The pathogenesis of chronic telogen hair loss (CTHL) remains incompletely understood, and the changes occurring in hair follicles are heterogeneous in both pathogenetic and histological terms, rendering the treatment of this condition a significant challenge for clinicians. This underscores the importance of further research in this fi eld and the search for effective therapies, one of which may involve osteopathic correction. The aim of the study : to evaluate the feasibility of incorporating osteopathic correction into the combined treatment of female patients with CTHL. Materials and methods . A prospective controlled randomized study was conducted at the Ā«Vash DoctorĀ» Clinic (Moscow region, Odintsovo) from January 2024 to September 2024. The study included 58 female patients diagnosed with telogen alopecia. Using randomization envelopes, participants were divided into two equal groups of 29 patients each: the main group and the control group. Patients in both groups received conventional combined conservative treatment as prescribed by a dermatologist. Patients in the main group additionally underwent osteopathic correction — 3 sessions at 14-day intervals. Results. In patients with CTHL, a reduction in hair density per cm 2 and hair diameter was observed, accompanied by decreased mechanical strength. Subclinical levels of depression and anxiety were also recorded. Despite the diverse etiological factors of CTHL no predominant somatic dysfunctions were identified in the osteopathic status of the study group. Both treatment regimens demonstrated clinical efficacy, with statistically significant increases in hair diameter and mechanical strength ( p <0,01). However, the inclusion of osteopathic correction resulted in a statistically significant increase in hair density per cm 2 ( p <0,01) and significantly higher mechanical strength values ( p <0,05). Conclusion . Incorporating osteopathic correction into the combined treatment of female patients with CTHL yields statistically more significant improvements in hair density per cm², mechanical strength, and reductions in depression and anxiety levels compared to conventional therapy alone. Further research in this area appears promising.
Background/Objectives: Treatment options for androgenic alopecia are still very limited and lack long-term efficacy. Dutasteride (DUT) has gained interest as a potent inhibitor of 5α-reductase, allowing for spaced applications, but … Background/Objectives: Treatment options for androgenic alopecia are still very limited and lack long-term efficacy. Dutasteride (DUT) has gained interest as a potent inhibitor of 5α-reductase, allowing for spaced applications, but DUT oral intake can cause serious adverse effects. Herein, we developed, characterized, and assessed the potential of DUT-loaded ethosomes with increasing ethanolic concentrations for hair follicle (HF) targeting to treat androgenic alopecia, hypothesizing that ethanol’s interaction with HFs’ sebum might increase DUT targeting to the HFs. Methods: Ethosomes were obtained using the water-dropping method. After a hydrodynamic size screening, a 30% ethanol concentration was fixed. Ethosomes with 30% ethanol were also prepared and had their ethanolic content removed by rotary evaporation for the evaluation of ethanol in targeting DUT to the HFs. The targeting factor (Tf) was calculated as the ratio between the DUT amount in HFs and the total DUT amount recovered from all skin layers after in vitro porcine skin penetration tests for 12 and 24 h. Results: The ethanolic concentration affected the vesicles’ size and the targeting potential. While the dried ethosomes could not increase DUT accumulation in the HFs at both time points (Tf: 0.27 in 12 h and Tf: 0.28 in 24 h), the presence of 30% ethanol in the vesicles increased the Tf from 0.28 (12 h) to 0.34 (24 h), significantly superior (p < 0.05) than the dried ethosome and control (Tf: 0.24) in 24 h. Conclusion: Ethosomes with a 30% ethanolic concentration were slightly more efficient in targeting HFs for dutasteride delivery.
Abstract Background: Seborrheic dermatitis (SD) is the most common concurrent disease in patients with androgenetic alopecia (AGA). There are inadequate data to determine whether there is a relationship between AGA … Abstract Background: Seborrheic dermatitis (SD) is the most common concurrent disease in patients with androgenetic alopecia (AGA). There are inadequate data to determine whether there is a relationship between AGA severity and SD severity. Aim and Objectives: This study aimed to investigate the presence and the severity of SD in patients with AGA, who were divided into groups based on the severity of AGA. Patients and Methods: We evaluated 311 patients aged ≄18 years who were diagnosed with AGA at the dermatology outpatient clinic between April and September 2023. Patients were divided into three groups according to AGA severity. We used the Clinical Severity Score Criteria to determine the severity of SD on the scalp. We subsequently compared the severity scores among the groups based on the severity of AGA. Results: The mean age was 41.5 ± 15.2 (range 18–85) years. Of these patients, 74 (23.8%) were female and 237 (76.2%) were male. SD was observed in 131 patients (42.1%). Among those with SD, 19.9% were female and 80.1% were male. As AGA severity increased, the prevalence of SD also increased ( P = 0.28). Furthermore, there was a statistically significant difference in the SD scores as the severity of AGA increased ( P < 0.001). Limitations: Small patient group and cross-sectional design. Conclusion: SD may affect the pathophysiology and severity of AGA.
A alopecia areata (AA) Ć© uma doenƧa autoimune caracterizada pela perda nĆ£o cicatricial dos cabelos, podendo evoluir para formas mais graves, como alopecia totalis e universalis. Recentemente, os inibidores da … A alopecia areata (AA) Ć© uma doenƧa autoimune caracterizada pela perda nĆ£o cicatricial dos cabelos, podendo evoluir para formas mais graves, como alopecia totalis e universalis. Recentemente, os inibidores da Janus quinase (JAK) surgiram como terapias promissoras, atuando na modulação da resposta imune envolvida na destruição dos folĆ­culos pilosos. Esta revisĆ£o bibliogrĆ”fica analisou estudos clĆ­nicos randomizados publicados entre 2016 e 2025, que investigaram a eficĆ”cia e seguranƧa de inibidores de JAK tópicos ou sistĆŖmicos no tratamento da AA. As buscas foram realizadas nas plataformas PubMed, Scielo e Google AcadĆŖmico. Foram incluĆ­dos estudos que utilizaram o escore SALT como principal medida de desfecho, sem restriƧƵes quanto Ć  idade, sexo, gravidade ou duração da doenƧa. No total, foram avaliados dados de 5.116 pacientes tratados com ritlecitinibe, baricitinibe, ruxolitinibe, deuruxolitinibe, tofacitinibe e brepocetinibe. Os resultados indicaram melhora significativa na cobertura capilar, especialmente com ritlecitinibe e baricitinibe, mesmo em pacientes com formas extensas da doenƧa. Os efeitos adversos foram, em sua maioria, leves a moderados e semelhantes entre os fĆ”rmacos, incluindo cefaleia, acne e infecƧƵes respiratórias. Observou-se que a interrupção do tratamento leva frequentemente Ć  perda dos resultados obtidos, indicando a necessidade de manutenção prolongada. Conclui-se que os inibidores de JAK representam uma alternativa eficaz no tratamento da AA severa, com perfil de seguranƧa aceitĆ”vel, embora estudos de longo prazo ainda sejam necessĆ”rios para estabelecer diretrizes terapĆŖuticas definitivas.
Abstract We report a rare case of scalp hair repigmentation after radiotherapy in a 76-year-old male. The patient had grey scalp hairs for over a decade, and was treated with … Abstract We report a rare case of scalp hair repigmentation after radiotherapy in a 76-year-old male. The patient had grey scalp hairs for over a decade, and was treated with radiotherapy, 45 Gy delivered over 25 fractions, for squamous cell carcinoma of the scalp and neck. He subsequently underwent a period of radiotherapy-induced alopecia and when his hair regrew four months later it was unexpectedly coloured orange to brown, his natural hair colour in his youth. There are limited reported cases of this phenomenon. This report adds to the limited literature, highlighting the role of hair follicle melanocytes and melanocyte stem cell plasticity in hair colour restoration, and how factors such as radiation may influence it.
Androgenetic alopecia (AGA) is a chronic and progressive hair loss disorder marked by follicular miniaturization and a shortened anagen phase. While androgenic and genetic factors contribute to its pathogenesis, increasing … Androgenetic alopecia (AGA) is a chronic and progressive hair loss disorder marked by follicular miniaturization and a shortened anagen phase. While androgenic and genetic factors contribute to its pathogenesis, increasing evidence highlights the importance of dysregulated molecular signaling in impaired hair follicle (HF) regeneration.This review explores the interconnected signaling pathways that govern HF cycling and regeneration-Wnt/β-catenin, Sonic Hedgehog (Shh), Bone Morphogenetic Protein (BMP), and Notch. Wnt/β-catenin activation initiates anagen by stimulating stem cell proliferation and follicle formation, while Shh supports follicular proliferation and morphogenesis. Notch regulates HF stem cell (HFSC) fate, and BMP enforces quiescence and catagen onset. Crucially, crosstalk between Wnt-BMP and Shh-Notch pathways ensures follicular homeostasis, highlighting the need to view these pathways as an integrated regulatory network.Recent therapeutic innovations focus on modulating these signaling cascades. Small molecules such as valproic acid and CHIR99021 activate Wnt signaling; smoothened agonists target Shh; and Noggin mimetics or BMP-neutralizing antibodies inhibit BMP activity. These approaches have shown promising outcomes in preclinical models, including mouse studies, in vitro HFSC systems, etc. Additionally, emerging gene editing technologies (e.g., CRISPR-Cas9) and stem cell-biomaterial integration offer regenerative strategies that move beyond symptomatic treatments like minoxidil or hair transplantation.Given that AGA is associated with androgen-mediated Wnt suppression and TGF-β activation, targeting these dysregulated networks presents a promising route for long-term management. A deeper understanding of pathway interactions lays the groundwork for precise, durable, and disease-modifying therapies in the evolving landscape of alopecia treatment.
Androgenetic alopecia (AGA) is characterized by the depletion or dormancy of hair follicle stem cells (HFSCs), leading to hair thinning and miniaturization. Reactivating the dormant HFSCs is a promising therapeutic … Androgenetic alopecia (AGA) is characterized by the depletion or dormancy of hair follicle stem cells (HFSCs), leading to hair thinning and miniaturization. Reactivating the dormant HFSCs is a promising therapeutic approach. Adrenergic β2 receptor (ADRB2) activation has been shown to promote hair growth in animal models via the Sonic Hedgehog (SHH) pathway, but its potential for treating clinical AGA patients remains unexamined. We investigated the role of the PI3K/AKT signaling pathway in AGA pathogenesis, focusing on the hair follicle-sympathetic nerve axis. The ADRB2 agonist, isoproterenol (ISO), was administered to assess its effects on AGA hair follicle organ culture model and HFSC proliferation. The mechanisms underlying these effects were explored by analyzing the PI3K/AKT/β-Catenin pathway. Our results showed abnormal PI3K/AKT pathway expression in AGA hair follicles, with associated defects in the hair follicle-sympathetic nerve axis. ISO treatment accelerated AGA hair follicle growth and promoted the proliferation of HFSC. Mechanistically, ISO facilitated the HFSC activation by modulating the PI3K/AKT/β-Catenin pathway. ISO effectively promotes hair growth in both animal models and AGA patients. ISO stimulating the proliferation of dormant cell population enriched in HFSC. This process was likely mediated by the PI3K/AKT/β-Catenin pathway. These findings provide novel insights into the reactivation of HFSCs and suggest that adrenergic signaling stimulation may be a promising strategy for managing hair loss.
Objective: Androgenetic alopecia (AGA) is a common type of hair loss worldwide. Currently, available treatment options for AGA show inconsistent results and may cause various undesirable side effects. Platelet-rich plasma … Objective: Androgenetic alopecia (AGA) is a common type of hair loss worldwide. Currently, available treatment options for AGA show inconsistent results and may cause various undesirable side effects. Platelet-rich plasma exosomes (PRP-Exo) is one of the therapeutic modalities that has shown satisfactory results to treat hair loss. This study aims to assess the effectiveness of minoxidil and PRP-Exo for AGA. Methods: An experimental investigation was conducted using alopecia BALB/c mice to examine hair follicle characteristics. Fourteen mice were divided into two groups, one group received daily topical application of 5% minoxidil, meanwhile, the other group received 0.1 ml injections of PRP-Exo on days 11, 18 and 25. Follicle density and the anagen: telogen ratio were evaluated histopathological. Results: The administration of PRP-Exo resulted in significantly different follicle density (68.61±7.64 vs. 40.14±11.60; p = 0.007) and anagen: telogen ratio (0.34±0.04 vs. 0.22±0.02; p = 0.009) compared to minoxidil. Conclusion: This investigation demonstrates that PRP-Exo effectively enhance both hair follicle density and the anagen: telogen ratio in the AGA mice model when compared to minoxidil 5%.
Objective: Androgenetic alopecia (AGA) is the world's most common type of hair loss caused by an exaggerated response to androgens. The pathophysiology of AGA has been extensively studied to date, … Objective: Androgenetic alopecia (AGA) is the world's most common type of hair loss caused by an exaggerated response to androgens. The pathophysiology of AGA has been extensively studied to date, but the process of developing small animal trials remains a challenge. Objective: This study aims to develop a testosterone-induced AGA mice model to facilitate future research related to AGA, either to understand the pathophysiology or to develop new therapeutic modalities. This AGA mice model may also be clinically useful, especially to facilitating drug testing for AGA therapies. Methods: This is a preliminary in vivo study to develop AGA mice model. This study used BALB/c white mice. The AGA model was induced by subcutaneous injection of testosterone. The subjects were divided into three different groups, group a (0.05 ml testosterone subcutaneous injection), group B (0.075 ml testosterone subcutaneous injection) and group C (0.1 ml testosterone subcutaneous injection). Dermal thickness (DT) and hair follicle density (HFD) were the assessment parameters used to determine the optimal testosterone dose to induce the AGA model. Results: BALB/c mice in group B obtained DT of 385.59 μm (p = 0.006) and HFD of 13.38/mm2 (p = 0.001), which were significantly lower than the other groups. This value is lower than group A with DT of 643.82 μm and HFD of 36.13/mm2 and group C with DT of 477.00 μm and HFD of 15.75/mm2. Conclusion: Testosterone at dose 0.075 ml with subcutaneous injection can produce the most ideal AGA mice model and most similar to the condition of dermis and hair follicles in AGA patients.
The development and replacement of hair play a significant role in the life history of animals. In recent years, retinoic-acid-related orphan receptor alpha (Rorα) has been found to participate in … The development and replacement of hair play a significant role in the life history of animals. In recent years, retinoic-acid-related orphan receptor alpha (Rorα) has been found to participate in the regulation of hair follicle development, yet the underlying mechanisms remain incompletely understood. This study aims to analyze the regulatory role of Rorα on the cytoskeleton of hair follicle stem cells (HFSCs). We treated HFSCs with a RORA agonist and subsequently analyzed differential gene expression using qPCR, Western blotting, and immunofluorescence, finding that agonist-induced activation of RORA suppressed the expression levels of cytoskeleton-related genes. Additionally, F-actin staining with phalloidin, followed by migration assays and wound healing tests for cell migration detection, revealed that this process affected the cytoskeletal state of HFSCs and inhibited their migration and adhesion capabilities. We further conducted interaction analyses using CUT&RUN combined with ddPCR and EMSA, demonstrating that RORA can bind to the promoter regions of the Actg1 gene and regulate their transcription. This study contributes to a comprehensive understanding of the regulatory processes involved in hair follicle development and may provide broader insights into the treatment of diseases such as alopecia.
Abstract Introduction: Hair loss is one of the most feared treatment side effects for women starting chemotherapy. Treatment-induced alopecia creates feelings of increased social stigma and isolation, emotional states correlated … Abstract Introduction: Hair loss is one of the most feared treatment side effects for women starting chemotherapy. Treatment-induced alopecia creates feelings of increased social stigma and isolation, emotional states correlated with poorer overall disease prognosis. Supporting quality of life during cancer treatment, including successful hair preservation via scalp cooling, has been shown to correlate with higher ratings of health-related well-being. Currently, the only option for reducing hair loss during chemotherapy is scalp cooling with devices like the Paxman and Dignicap, which are usually well-tolerated. This study aims to investigate the difference in reported symptoms and total symptom burden in women with breast cancer receiving scalp cooling interventions and matched controls during chemotherapy. Methods: In this ongoing IRB-approved study at Lankenau Medical Center, 25 patients have chosen to use scalp cooling during breast cancer treatment. These patients were matched by age and chemotherapy regimen to those who did not use scalp cooling. Our patient base typically has a high proportion of African Americans given that our medical center is located adjacent to West Philadelphia, a community with a 90 - 95% African American population. However, only 8% of patients in the cold cap group were African American compared to 36% of African American patients in the control group. With a high up-front co-pay, many patients of all races forego this supportive care. The average age was approximately 50 in both groups. At treatment visits participants completed the Modified Rotterdam Symptom Checklist; a self-report questionnaire rating 29 chemotherapy side effects on a scale of zero to three. Data from the first 50 patients was analyzed in GraphPad Prism 8.4.3 for relationships between factors and the patient’s total symptom burden, calculated as the total symptom checklist score at each visit. Wilcoxon matched pairs signed rank test (CI 95%) was used to assess the difference between total symptom burden in cold cap users and their matched controls. Results: Most patients who chose scalp cooling were younger and predominantly Caucasian. The total symptom burden was significantly lower (p<0.0002) among patients using scalp cooling compared to the matched controls. Of individual symptoms, there was a moderate reduction in reported tiredness even though the Paxman-using patients reported a moderately significantly higher level of difficulty sleeping. Patients using scalp cooling reported a significant reduction in appetite compared to their controls but had no significant weight loss. There was no significant difference in sexual interest between the two groups. Discussion and Conclusion: Cold cap systems have benefits beyond just aesthetics, use of scalp cooling interventions provide significant improvement in patient’s symptom ratings. Maintaining hair can contribute to a patient's sense of normalcy and self-esteem during a challenging time which can positively impact their overall quality of life and well-being. Even though scalp cooling had a positive effect by decreasing the overall symptom burden, individual symptoms that can be associated with emotionally related symptoms such as appetite, sleep, and sexual interest were not necessarily improved by the use of scalp cooling. The current co-pay system prevents many of our patients from the West Philadelphia community from taking advantage of this supportive car. We are currently in the process of reducing the economic barrier to access to scalp cooling to increase the diversity of the cohort and include other hair textures, a factor known to affect the efficiency of scalp cooling. Citation Format: Talar Telvizian, Kathryn J Fleck, Meghan Ely, Aarti l. Shevade, Zonera A. Ali, Arezoo Ghaneie, U. Margaretha Wallon. Beyond Aesthetics: Cold Cap Hair Preservation Correlates with Lower Chemotherapy Symptom Burden in Patients with Breast Cancer [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P4-01-03.
Abstract Introduction: The management of breast cancer during pregnancy requires complex decision making to optimize the health of the patient and minimize risks to the baby. Some systemic therapy agents, … Abstract Introduction: The management of breast cancer during pregnancy requires complex decision making to optimize the health of the patient and minimize risks to the baby. Some systemic therapy agents, such as HER2-targeted agents, are contraindicated in pregnancy, while for other agents there are less data. Doxorubicin + cyclophosphamide (AC) is a regimen that has been shown to be safe during pregnancy. However, hair loss is near universal without scalp cooling. There are no published reports of scalp cooling during pregnancy and the safety and activity of scalp cooling in pregnancy are unknown, though short term exposure to cold is not thought to be harmful. Clinical Case: A 38 year old woman palpated a mass in her right breast. Breast ultrasound showed 1.5 cm and 1.3 cm masses with benign-appearing axillary lymph nodes. US-guided core biopsy revealed a grade 2 invasive ductal carcinoma (IDC) ER+, PR+, HER2+. At the time of diagnosis, she was found to be 10 weeks pregnant and desired to continue the pregnancy. Since HER2-targeted therapy is contraindicated during pregnancy, the patient started neoadjuvant systemic therapy with AC and used scalp cooling for hair preservation starting cycle 1. She received C1D1 at 14 weeks gestation and completed 4 cycles without complication. She had nearly 100% of her hair after 4 cycles of AC. At 30 weeks gestation, she underwent right partial mastectomy and sentinel lymph node biopsy which showed 2.5 cm of grade 2 IDC with 10% cellularity, ER+/PR+/HER2+. She had 6.5 cm of grade 2-3 DCIS, 1/1 lymph nodes with isolated tumor cells, and negative margins. At 34 weeks gestation, the patient was induced and delivered a healthy baby girl. At 2 weeks postpartum she started weekly paclitaxel, trastuzumab and pertuzumab (THP). She continued to use scalp cooling with minimal hair loss (<5%) after 12 weeks of THP. She has completed adjuvant T-DM1 and experienced no further hair loss. Discussion: The diagnosis of breast cancer during pregnancy poses unique challenges both for treatment and symptom management. Data are limited in this space and largely from retrospective series, highlighting the need for careful monitoring and reporting of pregnant patients’ experiences with breast cancer treatment. Hair loss is one of the most visible and psychologically distressing side effects of chemotherapy. Multiple randomized trials have demonstrated the efficacy of scalp cooling in reducing chemotherapy related hair loss, with more than half of women who use scalp cooling retaining more than 50% of their hair. However, rates of hair preservation are significantly lower with anthracyclines (16% in the SCALP trial). To our knowledge, there are no published reports on scalp cooling during pregnancy. This case is notable given the remarkable success of hair preservation with AC during pregnancy. In addition, scalp cooling was well tolerated for this patient and she went on to deliver safely. We hypothesize her notable hair preservation may be due in part to pregnancy related hair changes. Many women report thicker hair during pregnancy, due to slowing of hair follicle cycling with more follicles staying in growth phase (anagen) and fewer hairs entering resting phase (telogen), which results in less shedding and hair loss. After pregnancy, more hair follicles enter telogen phase resulting in postpartum hair loss (telogen effluvium). During her post-partum taxane treatment, she experienced ∼5% hair loss, which may have represented telogen effluvium. This case demonstrates that scalp cooling can be safe and remarkably effective during pregnancy and should be considered in pregnant patients to mitigate the distress associated with alopecia. Citation Format: Kelsey Natsuhara, Annalisa Post, Michael D. Alvarado, Sally Fang-Tu, Gretchen Fulgencio, A. Jo Chien. A case report of successful hair preservation using scalp cooling with doxorubicin and cyclophosphamide during pregnancy [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P1-12-19.
Introduction and Objective: Alopecia is a potential adverse event of anti-obesity medications (AOMs). Rapid weight loss may result in deficiencies of key nutrients and act as a physiological stressor, potentially … Introduction and Objective: Alopecia is a potential adverse event of anti-obesity medications (AOMs). Rapid weight loss may result in deficiencies of key nutrients and act as a physiological stressor, potentially disrupting hair growth cycles and increasing hair shedding. This study aimed to evaluate the association between AOMs and risk of alopecia. Methods: PubMed, EMBASE, Cochrane Library, and Clinicaltrial.gov were searched from inception to December 2024. Randomized controlled trials (RCTs) that compared AOMs with placebo or active controls and reported alopecia events were included. The results were computed as odds ratios (OR) with 95% confidence intervals (CI) in random-effect model. Meta-regression analyses were performed to address potential influencing factors. Results: In total, 10 RCTs with 22840 participants were included. Compared with non-users, the use of AOMs was associated with an increased risk of alopecia (OR=3.12, 95%CI, 1.90 to 5.14). The risk of alopecia was much higher in the subgroup with obesity (OR=3.89, 95%CI, 2.37 to 6.37) when compared with the subgroup without obesity (OR=0.68, 95%CI, 0.16 to 2.86, p for subgroup difference=0.02). Meta-regression analyses suggested that greater body weight reduction percentage (β=-0.13, p=0.05) and greater body weight absolute reduction (β=-0.23, p=0.03) were associated with a higher risk of alopecia. However, younger age was associated with an elevated risk of alopecia (β=-0.20, p=0.02). Conclusion: AOMs were associated with an increased risk of alopecia, and the risk of alopecia increased with greater weight reduction. Our findings highlight the need for caution regarding the effects of rapid weight loss on hair health. Disclosure R. Jiao: None. C. Lin: None. Z. Li: None. Y. Guo: None. F. Lyu: None. W. Yang: None. X. Cai: None. L. Ji: None.
Background Hair follicle stem cells (HFSCs) play crucial roles in hair growth and are expected to be potential targets in regenerative medicine and tissue engineering. Method This study aims to … Background Hair follicle stem cells (HFSCs) play crucial roles in hair growth and are expected to be potential targets in regenerative medicine and tissue engineering. Method This study aims to investigate the positive effect on hair growth by the recombinant human collagen complex (RHC complex), composed of rhCOL III, rhCOL XVII, and rhCOL XXI, along with nicotinamide, both in vitro and in vivo , by HFSCs and rat models. The survival rate, function, and differentiation of HFSCs were investigated. Results The CCK-8 experiment showed that the RHC complex was non-toxic to HFSCs, and the cell survival rate exceeded 80% after 8 and 16 h of treatment. The ELISA method showed that the RHC complex significantly increased the intracellular vascular endothelial growth factor (VEGF) levels. In addition, the increase in the content of trichohyalin (a key structural protein of hair) indicates that the structure and function of hair follicles may be enhanced. The expression levels of β-integrin and p63 were significantly upregulated, which are crucial for cell adhesion, migration, and maintenance of HFSCs homeostasis. In the rat model, significant hair growth was observed after a 7-day treatment period. The period of vigorous hair growth in rats was selected for immunofluorescence, enzyme-linked immunosorbent assay (ELISA) and hematoxylin-eosin (HE) staining analysis. The results showed that the RHC complex could promote the expression of Integrin, Laminin and Perlecan, which were conducive to maintaining the stability of the microenvironment of HFSCs. Additionally it facilitated the migration and differentiation of HFSCs, as evidenced by an increased number of hair follicles in HE-stained skin tissues. In conclusion, the RHC complex exhibited high HFSCs survival rates and enhanced the expression of HFSCs-associated factors and basement membrane proteins. These properties make the RHC complex a promising novel ingredient for promoting hair growth, preventing hair loss, and maintaining hair health.
Androgenetic alopecia (AGA) is the most common form of patterned hair loss, exhibiting gender-specific clinical features. Recent studies highlight the importance of the skin microbiome in maintaining skin health, but … Androgenetic alopecia (AGA) is the most common form of patterned hair loss, exhibiting gender-specific clinical features. Recent studies highlight the importance of the skin microbiome in maintaining skin health, but the relationship between the hair follicle microbiome and hair loss, particularly AGA, remains understudied. Hair follicle layer samples were collected directly from the crown region of female pattern hair loss (FPHL), male pattern hair loss (MPHL), and healthy adult women (control) groups. Microbial DNA was extracted and analyzed using Illumina 16S rRNA V3–V4 gene amplicon sequencing. Alpha-diversity and beta-diversity analyses and taxonomic and functional profiling were conducted through relative abundance, LEfSe, and PICRUSt2 analyses. The alpha-diversity analysis showed a significant decrease in microbial richness in the hair loss groups. Unweighted UniFrac-based beta-diversity analysis revealed significant clustering between the control group and the FPHL group. Taxonomic profiling and LEfSe analysis identified differences in microbial composition and biomarkers. PICRUSt2 analysis further revealed altered pathways related to porphyrin metabolism, fatty acid biosynthesis, and steroid hormone metabolism. Additionally, differences in microbiome composition and potential functions were found between the FPHL and MPHL groups. This study provides comprehensive insights into the hair follicle microbiome, revealing unique microbial patterns and functional alterations associated with FPHL. Understanding these microbiome characteristics may contribute to targeted approaches for addressing AGA. Further research is warranted.
Immune privilege (IP) is a specialized immunological state that protects certain tissues, including the hair follicle (HF), from immune-mediated destruction. The maintenance of hair follicle immune privilege (HFIP) is crucial … Immune privilege (IP) is a specialized immunological state that protects certain tissues, including the hair follicle (HF), from immune-mediated destruction. The maintenance of hair follicle immune privilege (HFIP) is crucial for uninterrupted hair growth and is mediated by several mechanisms. These include the downregulation of major histocompatibility complex (MHC) class I molecules, the secretion of immunosuppressive cytokines such as transforming growth factor-beta (TGF-β) and alpha-melanocyte-stimulating hormone (α-MSH), and the recruitment of regulatory immune cells that suppress pro-inflammatory responses. Additionally, the blood-hair follicle barrier limits immune cell infiltration, further preserving immune privilege. However, in alopecia areata (AA), HFIP collapses triggering an autoimmune attack against follicular structures. This breakdown is marked by increased antigen presentation, heightened expression of MHC class I and II molecules, and an influx of autoreactive cytotoxic CD8+ T cells. These T cells, particularly those expressing the NKG2D receptor, recognize stress-induced ligands on follicular keratinocytes and initiate a cytotoxic response. Interferon-gamma (IFN-γ) and interleukin-15 (IL-15) play central roles in amplifying inflammation by activating the JAK-STAT signaling pathway, further promoting immune cell infiltration and follicular destruction. Additional immune cells, including natural killer cells, dendritic cells, and macrophages, contribute to disease pathogenesis by enhancing antigen presentation and sustaining the inflammatory cascade. Given the central role of HFIP collapse in AA, therapeutic strategies aimed at restoring immune privilege represent a promising avenue for long-term disease management. Future research should focus on identifying key molecular regulators of HFIP and developing targeted interventions to re-establish immune tolerance within the hair follicle.
Introduction Alopecia areata (AA) is a chronic autoimmune disorder causing non-scarring hair loss, which can range from isolated patches to complete scalp (alopecia totalis, AT) or body hair loss (alopecia … Introduction Alopecia areata (AA) is a chronic autoimmune disorder causing non-scarring hair loss, which can range from isolated patches to complete scalp (alopecia totalis, AT) or body hair loss (alopecia universalis, AU). It affects people of all ages, genders, and ethnicities. Around 10-20% of cases have a familial component, indicating a genetic predisposition. Symptoms often begin before age 40, with about half of patients experiencing onset in childhood, and it may coexist with other autoimmune diseases. The disease’s course is unpredictable, with spontaneous hair regrowth possible, though relapses are common, reaching a 100% relapse rate after 10-20 years. AA significantly affects quality of life, increasing the risk of anxiety and depression. Research has linked AA to autoimmune processes involving the JAK-STAT pathway, which promotes inflammation around hair follicles. Recent studies highlight the potential of JAK inhibitors as effective treatments. Material and methods An electronic literature search was performed using PubMed, Cochrane Library, and Evidence‑Based Medicine Reviews. Search terms included ā€˜alopecia areata’, ā€˜hair lossā€˜ , ā€˜JAK inhibitor’, ā€˜JAK-2 inhibitors’, ā€˜ Janus Kinase Inhibitorsā€˜, ā€˜tofacitinib’, ruxolitinib’, ā€˜baricitinib’ as keywords. The review focused on articles published in English from their inception until 2025. Conclusions Janus kinase (JAK) inhibitors represent a significant advancement in treating alopecia areata by specifically targeting the JAK/STAT pathway, which is linked to hair loss. Oral JAK inhibitors like have shown the most promising results. However, challenges remain, including the risk of relapse after therapy, side effects, and limited efficacy of topical formulations. Ongoing research aims to develop more selective JAK inhibitors and maintenance strategies while addressing high treatment costs.