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Nature Reviews. Disease Primers Mar 2017Alopecia areata is an autoimmune disorder characterized by transient, non-scarring hair loss and preservation of the hair follicle. Hair loss can take many forms ranging... (Review)
Review
Alopecia areata is an autoimmune disorder characterized by transient, non-scarring hair loss and preservation of the hair follicle. Hair loss can take many forms ranging from loss in well-defined patches to diffuse or total hair loss, which can affect all hair-bearing sites. Patchy alopecia areata affecting the scalp is the most common type. Alopecia areata affects nearly 2% of the general population at some point during their lifetime. Skin biopsies of affected skin show a lymphocytic infiltrate in and around the bulb or the lower part of the hair follicle in the anagen (hair growth) phase. A breakdown of immune privilege of the hair follicle is thought to be an important driver of alopecia areata. Genetic studies in patients and mouse models have shown that alopecia areata is a complex, polygenic disease. Several genetic susceptibility loci were identified to be associated with signalling pathways that are important to hair follicle cycling and development. Alopecia areata is usually diagnosed based on clinical manifestations, but dermoscopy and histopathology can be helpful. Alopecia areata is difficult to manage medically, but recent advances in understanding the molecular mechanisms have revealed new treatments and the possibility of remission in the near future.
Topics: Alopecia Areata; Environmental Exposure; Hair; Hair Follicle; Humans; Microbiota; Scalp; Stress, Psychological
PubMed: 28300084
DOI: 10.1038/nrdp.2017.11 -
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 -
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 -
Indian Journal of Dermatology,... 2018Androgenetic alopecia is the most common form of progressive hair loss in humans. A genetic predisposition and hormonal status are considered as major risk factors for... (Review)
Review
Androgenetic alopecia is the most common form of progressive hair loss in humans. A genetic predisposition and hormonal status are considered as major risk factors for this condition. Several recent advances in molecular biology and genetics have increased our understanding of the mechanisms of hair loss in androgenetic alopecia. We review these advances and examine the trends in the genetic and molecular aspects of androgenetic alopecia.
Topics: Alopecia; Epigenesis, Genetic; Finasteride; Genetic Predisposition to Disease; Genome-Wide Association Study; Hair; Hair Follicle; Humans; Minoxidil; Receptors, Androgen
PubMed: 29595184
DOI: 10.4103/ijdvl.IJDVL_262_17 -
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 -
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 -
Cells May 2019The use of stem cells has been reported to improve hair regrowth in several therapeutic strategies, including reversing the pathological mechanisms, that contribute to... (Review)
Review
Advances in Regenerative Stem Cell Therapy in Androgenic Alopecia and Hair Loss: Wnt pathway, Growth-Factor, and Mesenchymal Stem Cell Signaling Impact Analysis on Cell Growth and Hair Follicle Development.
The use of stem cells has been reported to improve hair regrowth in several therapeutic strategies, including reversing the pathological mechanisms, that contribute to hair loss, regeneration of hair follicles, or creating hair using the tissue-engineering approach. Although various promising stem cell approaches are progressing via pre-clinical models to clinical trials, intraoperative stem cell treatments with a one-step procedure offer a quicker result by incorporating an autologous cell source without manipulation, which may be injected by surgeons through a well-established clinical practice. Many authors have concentrated on adipose-derived stromal vascular cells due to their ability to separate into numerous cell genealogies, platelet-rich plasma for its ability to enhance cell multiplication and neo-angiogenesis, as well as human follicle mesenchymal stem cells. In this paper, the significant improvements in intraoperative stem cell approaches, from in vivo models to clinical investigations, are reviewed. The potential regenerative instruments and functions of various cell populaces in the hair regrowth process are discussed. The addition of Wnt signaling in dermal papilla cells is considered a key factor in stimulating hair growth. Mesenchymal stem cell-derived signaling and growth factors obtained by platelets influence hair growth through cellular proliferation to prolong the anagen phase (FGF-7), induce cell growth (ERK activation), stimulate hair follicle development (β-catenin), and suppress apoptotic cues (Bcl-2 release and Akt activation).
Topics: Adipocytes; Adipose Tissue; Adult; Alopecia; Hair; Hair Follicle; Humans; Intercellular Signaling Peptides and Proteins; Mesenchymal Stem Cells; Platelet-Rich Plasma; Regenerative Medicine; Stem Cell Transplantation; Stem Cells; Tissue Engineering; Wnt Signaling Pathway
PubMed: 31100937
DOI: 10.3390/cells8050466 -
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 -
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