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Drug Design, Development and Therapy 2019Minoxidil was first introduced as an antihypertensive medication and the discovery of its common adverse event, hypertrichosis, led to the development of a topical... (Review)
Review
Minoxidil was first introduced as an antihypertensive medication and the discovery of its common adverse event, hypertrichosis, led to the development of a topical formulation for promoting hair growth. To date, topical minoxidil is the mainstay treatment for androgenetic alopecia and is used as an off-label treatment for other hair loss conditions. Despite its widespread application, the exact mechanism of action of minoxidil is still not fully understood. In this article, we aim to review and update current information on the pharmacology, mechanism of action, clinical efficacy, and adverse events of topical minoxidil.
Topics: Animals; Antihypertensive Agents; Hair; Humans; Hypertrichosis; Minoxidil; Molecular Structure; Sulfotransferases
PubMed: 31496654
DOI: 10.2147/DDDT.S214907 -
Nature Protocols May 2022Human skin uses millions of hairs and glands distributed across the body surface to function as an external barrier, thermoregulator and stimuli sensor. The large-scale... (Review)
Review
Human skin uses millions of hairs and glands distributed across the body surface to function as an external barrier, thermoregulator and stimuli sensor. The large-scale generation of human skin with these appendages would be beneficial, but is challenging. Here, we describe a detailed protocol for generating hair-bearing skin tissue entirely from a homogeneous population of human pluripotent stem cells in a three-dimensional in vitro culture system. Defined culture conditions are used over a 2-week period to induce differentiation of pluripotent stem cells to surface ectoderm and cranial neural crest cells, which give rise to the epidermis and dermis, respectively, in each organoid unit. After 60 d of incubation, the skin organoids produce hair follicles. By day ~130, the skin organoids reach full complexity and contain stratified skin layers, pigmented hair follicles, sebaceous glands, Merkel cells and sensory neurons, recapitulating the cell composition and architecture of fetal skin tissue at week 18 of gestation. Skin organoids can be maintained in culture using this protocol for up to 150 d, enabling the organoids to be used to investigate basic skin biology, model disease and, further, reconstruct or regenerate skin tissue.
Topics: Cell Differentiation; Hair; Hair Follicle; Humans; Organoids; Pluripotent Stem Cells; Skin
PubMed: 35322210
DOI: 10.1038/s41596-022-00681-y -
Actas Dermo-sifiliograficas Jan 2023Alopecia areata is an autoimmune disease that affects the hair follicle and can present as bald patches on the scalp and hair loss in other parts of the body. Diagnosis... (Review)
Review
Alopecia areata is an autoimmune disease that affects the hair follicle and can present as bald patches on the scalp and hair loss in other parts of the body. Diagnosis is clinical but can be aided by trichoscopy, a simple, rapid technique that reduces the need for invasive procedures and can also help with monitoring treatment response. We review the usefulness of trichoscopy in alopecia areata. The most common trichoscopic findings are yellow dots, black dots, exclamation mark hairs, short vellus hairs, and coudability hairs. Other, less common, findings can also help establish a diagnosis. Good response to treatment is indicated by the disappearance of black dots, broken hairs, and exclamation mark hairs. The observation of yellow dots, by contrast, indicates chronic disease and poor response to treatment.
Topics: Humans; Alopecia Areata; Dermoscopy; Hair; Alopecia; Hair Follicle; Hair Diseases
PubMed: 36067826
DOI: 10.1016/j.ad.2022.08.018 -
The Journal of Investigative Dermatology Oct 2022Skin wounds in adult mammals typically heal with a fibrotic scar and fail to restore ectodermal appendages, such as hair follicles or adipose tissue. Intriguingly, new... (Review)
Review
Skin wounds in adult mammals typically heal with a fibrotic scar and fail to restore ectodermal appendages, such as hair follicles or adipose tissue. Intriguingly, new hair follicles regenerate in the center of large full-thickness wounds of mice in a process called wound-induced hair neogenesis (WIHN). WIHN is followed by neogenesis of dermal adipose tissue. Both neogenic events reactivate embryonic-like cellular and molecular programs. The WIHN model provides a platform for studying mammalian regeneration, and findings from this model could instruct future regenerative medicine interventions for treating wounds and alopecia. Since Ito et al. rediscovered WIHN 15 years ago, numerous investigators have worked on the WIHN model using varying wounding protocols and model interpretations. Because a variety of factors, including environmental variables and choice of mouse strains, can affect the outcomes of a WIHN study, the purpose of this article is to provide an overview of the experimental variables that impact WIHN so that experiments between laboratories can be compared in a meaningful manner.
Topics: Animals; Hair; Hair Follicle; Mammals; Mice; Mice, Inbred C57BL; Regeneration; Skin; Wound Healing
PubMed: 36153062
DOI: 10.1016/j.jid.2022.07.013 -
Nature Jun 2020The skin is a multilayered organ, equipped with appendages (that is, follicles and glands), that is critical for regulating body temperature and the retention of bodily...
The skin is a multilayered organ, equipped with appendages (that is, follicles and glands), that is critical for regulating body temperature and the retention of bodily fluids, guarding against external stresses and mediating the sensation of touch and pain. Reconstructing appendage-bearing skin in cultures and in bioengineered grafts is a biomedical challenge that has yet to be met. Here we report an organoid culture system that generates complex skin from human pluripotent stem cells. We use stepwise modulation of the transforming growth factor β (TGFβ) and fibroblast growth factor (FGF) signalling pathways to co-induce cranial epithelial cells and neural crest cells within a spherical cell aggregate. During an incubation period of 4-5 months, we observe the emergence of a cyst-like skin organoid composed of stratified epidermis, fat-rich dermis and pigmented hair follicles that are equipped with sebaceous glands. A network of sensory neurons and Schwann cells form nerve-like bundles that target Merkel cells in organoid hair follicles, mimicking the neural circuitry associated with human touch. Single-cell RNA sequencing and direct comparison to fetal specimens suggest that the skin organoids are equivalent to the facial skin of human fetuses in the second trimester of development. Moreover, we show that skin organoids form planar hair-bearing skin when grafted onto nude mice. Together, our results demonstrate that nearly complete skin can self-assemble in vitro and be used to reconstitute skin in vivo. We anticipate that our skin organoids will provide a foundation for future studies of human skin development, disease modelling and reconstructive surgery.
Topics: Animals; Ectoderm; Female; Hair; Hair Color; Hair Follicle; Head; Heterografts; Humans; Mice; Mice, Nude; Organoids; Pluripotent Stem Cells; RNA-Seq; Single-Cell Analysis; Skin; Skin Transplantation
PubMed: 32494013
DOI: 10.1038/s41586-020-2352-3 -
BMB Reports Jan 2023Hair follicles in the skin undergo cyclic rounds of regeneration, degeneration, and rest throughout life. Stem cells residing in hair follicles play a pivotal role in... (Review)
Review
Hair follicles in the skin undergo cyclic rounds of regeneration, degeneration, and rest throughout life. Stem cells residing in hair follicles play a pivotal role in maintaining tissue homeostasis and hair growth cycles. Research on hair follicle aging and age-related hair loss has demonstrated that a decline in hair follicle stem cell (HFSC) activity with aging can decrease the regeneration capacity of hair follicles. This review summarizes our understanding of how age-associated HFSC intrinsic and extrinsic mechanisms can induce HFSC aging and hair loss. In addition, we discuss approaches developed to attenuate ageassociated changes in HFSCs and their niches, thereby promoting hair regrowth. [BMB Reports 2023; 56(1): 2-9].
Topics: Humans; Hair Follicle; Hair; Aging; Alopecia; Stem Cells
PubMed: 36379515
DOI: 10.5483/BMBRep.2022-0183 -
Cell Stem Cell Mar 2020Skin homeostasis is orchestrated by dozens of cell types that together direct stem cell renewal, lineage commitment, and differentiation. Here, we use single-cell RNA...
Skin homeostasis is orchestrated by dozens of cell types that together direct stem cell renewal, lineage commitment, and differentiation. Here, we use single-cell RNA sequencing and single-molecule RNA FISH to provide a systematic molecular atlas of full-thickness skin, determining gene expression profiles and spatial locations that define 56 cell types and states during hair growth and rest. These findings reveal how the outer root sheath (ORS) and inner hair follicle layers coordinate hair production. We found that the ORS is composed of two intermingling but transcriptionally distinct cell types with differing capacities for interactions with stromal cell types. Inner layer cells branch from transcriptionally uncommitted progenitors, and each lineage differentiation passes through an intermediate state. We also provide an online tool to explore this comprehensive skin cell atlas, including epithelial and stromal cells such as fibroblasts, vascular, and immune cells, to spur further discoveries in skin biology.
Topics: Animals; Cell Differentiation; Hair; Hair Follicle; Mice; Skin
PubMed: 32109378
DOI: 10.1016/j.stem.2020.01.012 -
Current Cardiology Reports Aug 2019This review focuses on the concentration of cortisol in human hair as a biomarker of chronic stress in cardiovascular disease (CVD). We outline the cardiovascular... (Review)
Review
PURPOSE OF REVIEW
This review focuses on the concentration of cortisol in human hair as a biomarker of chronic stress in cardiovascular disease (CVD). We outline the cardiovascular consequences of cortisol excess and provide a comprehensive overview of recent studies investigating the relationship of hair cortisol with CVD. In addition, clinical implications and limitations of the evidence are discussed, together with directions for future research.
RECENT FINDINGS
Hair cortisol may be a reliable biomarker of chronic stress since it provides quantification of total cortisol secreted into hair over several weeks. A growing body of evidence suggests that elevated hair cortisol levels are associated with both the incidence of CVD and poorer recovery and treatment outcomes. Moreover, increased hair cortisol concentration has been linked with established cardiometabolic risk factors for CVD including high blood pressure, diabetes, and adiposity. Hair cortisol is a promising biomarker of chronic cortisol excess which may contribute to both the pathogenesis and prognosis of CVD. However, the current evidence relies on small-scale cross-sectional studies. Further research adopting longitudinal designs across larger samples of CVD patients and healthy participants is required to inform the development of novel evidence-based interventions.
Topics: Biomarkers; Cardiovascular Diseases; Chronic Disease; Hair; Humans; Hydrocortisone; Saliva; Stress, Physiological; Stress, Psychological
PubMed: 31471749
DOI: 10.1007/s11886-019-1208-7 -
Nature Jun 2023Niche signals maintain stem cells in a prolonged quiescence or transiently activate them for proper regeneration. Altering balanced niche signalling can lead to...
Niche signals maintain stem cells in a prolonged quiescence or transiently activate them for proper regeneration. Altering balanced niche signalling can lead to regenerative disorders. Melanocytic skin nevi in human often display excessive hair growth, suggesting hair stem cell hyperactivity. Here, using genetic mouse models of nevi, we show that dermal clusters of senescent melanocytes drive epithelial hair stem cells to exit quiescence and change their transcriptome and composition, potently enhancing hair renewal. Nevus melanocytes activate a distinct secretome, enriched for signalling factors. Osteopontin, the leading nevus signalling factor, is both necessary and sufficient to induce hair growth. Injection of osteopontin or its genetic overexpression is sufficient to induce robust hair growth in mice, whereas germline and conditional deletions of either osteopontin or CD44, its cognate receptor on epithelial hair cells, rescue enhanced hair growth induced by dermal nevus melanocytes. Osteopontin is overexpressed in human hairy nevi, and it stimulates new growth of human hair follicles. Although broad accumulation of senescent cells, such as upon ageing or genotoxic stress, is detrimental for the regenerative capacity of tissue, we show that signalling by senescent cell clusters can potently enhance the activity of adjacent intact stem cells and stimulate tissue renewal. This finding identifies senescent cells and their secretome as an attractive therapeutic target in regenerative disorders.
Topics: Animals; Mice; Hair; Hair Follicle; Hyaluronan Receptors; Melanocytes; Nevus; Osteopontin; Stem Cells; Signal Transduction
PubMed: 37344645
DOI: 10.1038/s41586-023-06172-8 -
Frontiers in Endocrinology 2021Cyclic Cushing's syndrome (also known as intermittent or periodic) is a disease characterized by periods of transient hypercortisolemia shifting into periods of normo-... (Review)
Review
Cyclic Cushing's syndrome (also known as intermittent or periodic) is a disease characterized by periods of transient hypercortisolemia shifting into periods of normo- and/or hypocortisolemia. Diagnosis of cyclic Cushing's syndrome is based on at least three periods of confirmed hypercortisolemia interspersed by two periods of normocortisolemia. Cyclic Cushing's syndrome is one of the greatest challenges in modern endocrinology due to its diverse clinical picture, unpredictable duration and frequency of phases, and various etiologies. We discuss a diagnostic algorithm for periodic hypercortisolemia with special regard to hair cortisol analysis and desmopressin stimulation test which both seem to be helpful in finding the correct answer.
Topics: Animals; Cushing Syndrome; Hair; Humans; Hydrocortisone
PubMed: 33967962
DOI: 10.3389/fendo.2021.658429