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1.
Sud Med Ekspert ; 62(2): 22-25, 2019.
Artigo em Russo | MEDLINE | ID: mdl-31213587

RESUMO

The objective of the present study was to optimize genotyping of nuclear DNA contained in human hair. The most efficient procedures for DNA isolation and typing are described taking into consideration the hair growth phase, the epithelial tissue conditions, and the number of nuclei in the near-root ends of the hair. The recommendations for the expert interpretation of the results of the molecular-genetic investigations are proposed.


Assuntos
Núcleo Celular/genética , Impressões Digitais de DNA , DNA/isolamento & purificação , Genótipo , Cabelo/citologia , Humanos
2.
Int J Mol Sci ; 20(8)2019 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-30991711

RESUMO

Adiponectin (APN), released mainly from adipose tissue, is a well-known homeostatic factor for regulating glucose levels, lipid metabolism, and insulin sensitivity. A recent study showed that human hair follicles express APN receptors and the presence of APN-mediated hair growth signaling, thereby suggesting that APN is a potent hair growth-promoting adipokine. Previously, kojyl cinnamate ester derivatives (KCEDs) were synthesized in our institute as new anti-aging or adiponectin-/adipogenesis-inducing compounds. Here, we tested the activity of these derivatives to induce endogenous APN secretion. Among the derivatives, KCED-1 and KCED-2 showed improved activity in inducing APN mRNA expression, secretion of APN protein, and adipogenesis in human subcutaneous fat cells (hSCFs) when compared with the effects of Seletinoid G, a verified APN inducer. When human follicular dermal papilla cells were treated with the culture supernatant of KCED-1- or KCED-2-treated hSCFs, the mRNA expression of APN-induced hair growth factors such as insulin-like growth factor, hepatocyte growth factor, and vascular endothelial growth factor was upregulated compared with that in the control. Taken together, our study shows that among kojyl cinnamate ester derivatives, KCED-1, KCED-2, as well as Seletinoid G are effective inducers of endogenous APN production in subcutaneous fat tissues, which may in turn contribute to the promotion of hair growth in the human scalp.


Assuntos
Adiponectina/genética , Cinamatos/farmacologia , Folículo Piloso/efeitos dos fármacos , Regulação para Cima/efeitos dos fármacos , Adipogenia/efeitos dos fármacos , Adiponectina/metabolismo , Linhagem Celular , Cinamatos/química , Ésteres/química , Ésteres/farmacologia , Cabelo/citologia , Cabelo/efeitos dos fármacos , Cabelo/crescimento & desenvolvimento , Cabelo/metabolismo , Folículo Piloso/citologia , Folículo Piloso/crescimento & desenvolvimento , Folículo Piloso/metabolismo , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo
3.
Biomater Sci ; 7(4): 1299-1310, 2019 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-30821312

RESUMO

We demonstrated that the topical combined use of sponge Haliclona sp. spicules (SHS) and flexible liposomes (FL), referred to as SFLS (SHS-Flexible Liposomes combined System), can result in synergy to improve the skin absorption and deposition of hyaluronic acid (HA), especially in deep skin layers, both in vitro and in vivo. SHS treatment can result in skin micro-channels which are continuous, deep enough (48.6 ± 13.5 µm) and available in large quantities (850 ± 125 micro-channels per mm2). These micro-channels gradually closed up in 120 h and also allowed the intact vesicles of flexible liposomes and vesicle-bound or vesicle-encapsulated HA to penetrate into the skin-deep layers under the driving force of transdermal osmotic gradients. Specifically, SFLS topical application enhanced the penetration of FITC-HA (MW: 250 kDa) into porcine skin in vitro up to 23.2 ± 3.7%, which is 19.4 ± 3.1-fold (p < 0.001) that of a Phosphate Buffered Saline (PBS) group, 3.4 ± 0.5-fold (p < 0.01) that of an SHS group and 3.6 ± 0.6-fold (p < 0.01) that from the combined use of a Dermaroller and flexible liposomes. Moreover, SFLS can lead to significantly enhanced skin deposition of HA in all skin layers, especially in deep skin layers: up to 86.8 ± 4.1% of HA absorbed by skin was accumulated in deep skin layers. The effectiveness of SFLS topical application was also confirmed in vivo by using BALB/c mice. In addition, a skin irritation and toxicity study showed that the SFLS treatment may cause very minimal redness and the skin can recover in a short time. In sum, the combined use of SHS and FL (SFLS) offers a promising strategy to safely and effectively improve the skin delivery of hydrophilic biomacromolecules such as HA.


Assuntos
Ácido Hialurônico/química , Poríferos/química , Pele/química , Animais , Feminino , Cabelo/química , Cabelo/citologia , Ácido Hialurônico/administração & dosagem , Lipossomos/química , Camundongos , Camundongos Endogâmicos BALB C , Pele/citologia , Absorção Cutânea , Suínos
4.
Micron ; 119: 109-116, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30711746

RESUMO

There have been many studies about the formation, storage, transport and degradation of melanosomes in epidermal melanocytes but studies of melanocytes and melanosomes in fetal hair follicles (HFs) have been limited and ambiguous. The goal of this study was to investigate the distribution of melanocytes and the degradation of melanosomes in fetal HFs. After obtaining approval and informed consent for the study, a scalp specimen from a 5 month gestational age fetus was obtained and was divided into two parts. One part was subjected to immunohistochemical staining with the melanocyte-specific marker HMB-45 and was then observed by light microscopy to detect the distribution of melanocytes in HFs. The other part underwent conventional processing for transmission electron microcopy (TEM). Subsequently, the morphology of melanosomes in HF melanocytes and their degradation in cortical keratinocytes were observed. Immunohistochemically, scattered round melanocytes lacking dendrites were mainly observed along the outer root sheath of the lower part of the HF. A few fusiform or tri-dendritic melanocytes were located at the bottom of the hair bulbs. Significantly melanized melanocytes with multiple dendrites were concentrated in the pigmented area in the center of the hair bulbs, only above the dermal papilla. Analysis by TEM revealed melanocytes containing melanosomes at all stages of development. Autophagosomes containing stage mature IV melanosomes were observed in some melanocytes. Many phagolysosomes containing numerous melanosomes were observed in the cortical keratinocytes. Some phagolysosomes were concentrically surrounded by 3-5 layers of endoplasmic reticulum. Melanosomes that had been degraded or were being degraded in phagolysosomes in keratinocytes had lost their integrity and had become an ill-defined melanosomal dust that were arranged irregularly. Partial melanin particles were released into the cytosol. Melanocytes in different regions of fetal HFs had different morphologies and were at various stages of differentiation. Fetal HF melanocytes contained not only melanosomes at different developmental stages, but autophagosomes were seen occasionally. Melanosomes were degraded into irregular pigment particles in the phagolysosomes of cortical keratinocytes. These results provide important clues to elucidate the mechanism of melanosome biodegradation.


Assuntos
Folículo Piloso/citologia , Cabelo/citologia , Melanócitos/citologia , Melanócitos/metabolismo , Melanossomas/metabolismo , Biópsia , Biotransformação , Humanos , Imuno-Histoquímica , Queratinócitos/metabolismo , Queratinócitos/ultraestrutura , Lisossomos/metabolismo , Lisossomos/ultraestrutura , Melanócitos/ultraestrutura , Microscopia , Microscopia Eletrônica de Varredura , Couro Cabeludo
5.
Skin Res Technol ; 25(4): 447-455, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30614573

RESUMO

OBJECTIVES: To investigate the characteristics of hairs in Female pattern hair loss (FPHL) patients and healthy females in Southern China. MATERIALS AND METHODS: Three fundamental hair parameters in different scalp areas of 90 Southern Chinese FPHL patients and 83 healthy controls were analyzed by phototrichogram. RESULTS: Female pattern hair loss patients showed reduced hair density, hair diameter, and terminal/vellus hair ratio. The reduction correlated with the severity of Ludwig staging. Midscalp was the most affected area in FPHL, but occipital and temporal sites were also involved. In normal women, the highest hair density was observed in midscalp, followed by occipital and temporal areas. Peak hair density at midscalp sites was reached at 20s group, then declined with age. Maximum hair diameter at midscalp and occipital sites occurred in 40s group. Terminal/vellus hair ratio tended to increase with age and peak on 50-60s group. CONCLUSION: Reduced hair density and hair diameter, and miniaturization of hair follicles are the characteristics of FPHL in Southern Chinese women. Occipital and temporal sites are also affected in FPHL. Age-associated changes might have an influence on the hair condition. The values of hair parameters obtained in this study will help to establish reference data for better evaluation of hair disorders.


Assuntos
Alopecia/classificação , Folículo Piloso/crescimento & desenvolvimento , Couro Cabeludo/diagnóstico por imagem , Adulto , Alopecia/patologia , Grupo com Ancestrais do Continente Asiático/etnologia , Contagem de Células , Feminino , Cabelo/anormalidades , Cabelo/citologia , Cabelo/crescimento & desenvolvimento , Folículo Piloso/diagnóstico por imagem , Folículo Piloso/patologia , Humanos , Pessoa de Meia-Idade , Couro Cabeludo/patologia , Índice de Gravidade de Doença
6.
Nanomedicine ; 15(1): 70-85, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30201489

RESUMO

Recent progress in hair follicle regeneration and alopecia treatment necessitates revisiting the concepts and approaches. In this sense, there is a need for shedding light on the clinical and surgical therapies benefitting from nanobiomedicine. From this perspective, this review attempts to recognize requirements upon which new hair therapies are grounded; to underline shortcomings and opportunities associated with recent advanced strategies for hair regeneration; and most critically to look over hair regeneration from nanomaterials and pluripotent stem cell standpoint. It is noteworthy that nanotechnology is able to illuminate a novel path for reprogramming cells and controlled differentiation to achieve the desired performance. Undoubtedly, this strategy needs further advancement and a lot of critical questions have yet to be answered. Herein, we introduce the salient features, the hurdles that must be overcome, the hopes, and practical constraints to engineer stem cell niches for hair follicle regeneration.


Assuntos
Alopecia/terapia , Cabelo/citologia , Regeneração , Células-Tronco/citologia , Engenharia Tecidual , Animais , Diferenciação Celular , Cabelo/fisiologia , Humanos
7.
Int J Biol Macromol ; 126: 11-17, 2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-30576733

RESUMO

In this study, the effects of chitosan and surface-deacetylated chitin nanofibrils (SDACNFs) on hair growth were evaluated. In human follicle dermal papilla cells in vitro, chitosan and SDACNFs were shown to increase cell growth on day 3 after the initiation of treatment, together with an increase in the production of fibroblast growth factor-7 (FGF-7) by these cells on day 3. Furthermore, in an in vivo study in mice, chitosan and SDACNF application promoted hair growth. The number of anagen follicles significantly increased compared with that in the control group, whereas the number of telogen follicles significantly decreased in the chitosan and SDACNF groups. In the chitosan and SDACNFs groups, moreover, the expression levels of FGF-7 and Sonic hedgehog were significantly upregulated in hair follicles. Overall, our results demonstrated that chitosan and SDACNFs promoted hair growth and therefore may have applications as novel therapeutic agents for the treatment of hair loss in patients.


Assuntos
Quitina/farmacologia , Quitosana/farmacologia , Cabelo/crescimento & desenvolvimento , Nanofibras/química , Acetilação , Animais , Proliferação de Células/efeitos dos fármacos , Cabelo/citologia , Cabelo/efeitos dos fármacos , Folículo Piloso/citologia , Folículo Piloso/efeitos dos fármacos , Proteínas Hedgehog/metabolismo , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/biossíntese , Camundongos Endogâmicos C57BL , Propriedades de Superfície
8.
J Dermatol Sci ; 92(1): 18-29, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30146106

RESUMO

BACKGROUND: Previous studies demonstrated that adipose-derived stem cells (ASCs) can promote hair growth, but unmet needs exist for enhancing ASC hair inductivity. OBJECTIVE: Therefore, we introduced three trichogenic factors platelet-derived growth factor-A, SOX2, and ß-catenin to ASCs (tfASCs) and evaluated whether tfASCs have similar characteristics as dermal papilla (DP) cells. METHOD: Global gene expression was examined using NGS analysis. Telogen-to-anagen induction, vibrissae hair follicle organ culture and patch assay were used. RESULTS: tfASC cell size is smaller than that of ASCs, and they exhibit short doubling time. tfASCs also resist aging and can be expanded until passage 12. Cell proportion in S and G2/M increases in tfASCs, and tfASCs express high mRNA levels of cell cycle related genes. The mRNA expression of DP markers was notably higher in tfASCs. Moreover, NGS analysis revealed that the global gene expression of tfASCs is similar to that of DP cells. The injection of tfASCs accelerated the telogen-to-anagen transition and conditioned medium of tfASCs increased the anagen phase of vibrissal hair follicles. Finally, we found that the injection of 3D-cultured tfASCs at p 9 generated new hair follicles in nude mice. CONCLUSION: Collectively, these results indicate that 1) tfASCs have similar characteristics as DP cells, 2) tfASCs have enhanced hair-regenerative potential compared with ASCs, and 3) tfASCs even at late passage can make new hair follicles in a hair reconstitution assay. Because DP cells are difficult to isolate/expand and ASCs have low hair inductivity, tfASCs and tfASC-CM are clinically good candidates for hair regeneration.


Assuntos
Diferenciação Celular , Cabelo/citologia , Fator de Crescimento Derivado de Plaquetas/metabolismo , Fatores de Transcrição SOXB1/metabolismo , Células-Tronco/metabolismo , Gordura Subcutânea/citologia , beta Catenina/metabolismo , Animais , Pontos de Checagem do Ciclo Celular , Proliferação de Células , Tamanho Celular , Células Cultivadas , Regulação da Expressão Gênica no Desenvolvimento , Cabelo/crescimento & desenvolvimento , Cabelo/transplante , Humanos , Camundongos Endogâmicos C3H , Camundongos Nus , Fenótipo , Fator de Crescimento Derivado de Plaquetas/genética , Fatores de Transcrição SOXB1/genética , Transplante de Células-Tronco , Transfecção , beta Catenina/genética
9.
J Cell Physiol ; 233(11): 9015-9030, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-29923313

RESUMO

Human hair dermal papilla (DP) cells are specialized mesenchymal cells that play a pivotal role in hair regeneration and hair cycle activation. The current study aimed to first develop three-dimensional (3D) DP spheroids (DPS) with or without a silk-gelatin (SG) microenvironment, which showed enhanced DP-specific gene expression, resulting in enhanced extracellular matrix (ECM) production compared with a monolayer culture. We tested the feasibility of using this DPS model for drug screening by using minoxidil, which is a standard drug for androgenic alopecia. Minoxidil-treated DPS showed enhanced expression of growth factors and ECM proteins. Further, an attempt has been made to establish an in vitro 3D organoid model consisting of DPS encapsulated by SG hydrogel and hair follicle (HF) keratinocytes and stem cells. This HF organoid model showed the importance of structural features, cell-cell interaction, and hypoxia akin to in vivo HF. The study helped to elucidate the molecular mechanisms to stimulate cell proliferation, cell viability, and elevated expression of HF markers as well as epithelial-mesenchymal crosstalks, demonstrating high relevance to human HF biology. This simple in vitro DP organoid model system has the potential to provide significant insights into the underlying mechanisms of HF morphogenesis, distinct molecular signals relevant to different stages of the hair cycle, and hence can be used for controlled evaluation of the efficacy of new drug molecules.


Assuntos
Folículo Piloso/crescimento & desenvolvimento , Cabelo/crescimento & desenvolvimento , Células-Tronco Mesenquimais/citologia , Organoides/crescimento & desenvolvimento , Diferenciação Celular/genética , Proliferação de Células/genética , Células Cultivadas , Derme/citologia , Derme/crescimento & desenvolvimento , Transição Epitelial-Mesenquimal/genética , Feminino , Cabelo/citologia , Folículo Piloso/citologia , Humanos , Queratinócitos/citologia , Queratinócitos/metabolismo , Organoides/citologia , Regeneração/genética
10.
J Cell Biol ; 217(6): 2185-2204, 2018 06 04.
Artigo em Inglês | MEDLINE | ID: mdl-29602800

RESUMO

The microRNA (miRNA)-200 (miR-200) family is highly expressed in epithelial cells and frequently lost in metastatic cancer. Despite intensive studies into their roles in cancer, their targets and functions in normal epithelial tissues remain unclear. Importantly, it remains unclear how the two subfamilies of the five-miRNA family, distinguished by a single nucleotide within the seed region, regulate their targets. By directly ligating miRNAs to their targeted mRNA regions, we identify numerous miR-200 targets involved in the regulation of focal adhesion, actin cytoskeleton, cell cycle, and Hippo/Yap signaling. The two subfamilies bind to largely distinct target sites, but many genes are coordinately regulated by both subfamilies. Using inducible and knockout mouse models, we show that the miR-200 family regulates cell adhesion and orientation in the hair germ, contributing to precise cell fate specification and hair morphogenesis. Our findings demonstrate that combinatorial targeting of many genes is critical for miRNA function and provide new insights into miR-200's functions.


Assuntos
Cabelo/citologia , Cabelo/crescimento & desenvolvimento , MicroRNAs/metabolismo , Morfogênese , Citoesqueleto de Actina/metabolismo , Junções Aderentes/metabolismo , Animais , Sequência de Bases , Adesão Celular , Ciclo Celular , Linhagem da Célula , Movimento Celular , Núcleo Celular/metabolismo , Proliferação de Células , Adesões Focais/metabolismo , Folículo Piloso/crescimento & desenvolvimento , Folículo Piloso/metabolismo , Camundongos Knockout , MicroRNAs/genética , Fenótipo , Transporte Proteico , Transdução de Sinais , Pele/metabolismo
11.
Pigment Cell Melanoma Res ; 31(5): 630-635, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29488689

RESUMO

Various changes appear in hair by aging, and graying is the most remarkable one. Changes in melanocytes have been well studied as the cause; however, little is known about the change in melanosomes which have a role of carrying melanin pigments into hair shafts. Using pigmented hairs of Japanese females from their age of 4-75, I isolated melanosomes and observed them. As a result, I found a significant change in the morphology of hair melanosomes with age. They were ellipsoidal on the whole and there was no age dependence in the major axis, while the minor axis significantly increased and its frequency distribution broadened with age. The anticipated volume of the melanosome of the oldest person hairs was about twice larger than that of child hairs. This enlargement of melanosome seems to be a cause of the age-related color change in pigmented hairs from brown to black.


Assuntos
Envelhecimento , Cabelo/ultraestrutura , Melaninas/metabolismo , Melanossomas/ultraestrutura , Pigmentação , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Cabelo/citologia , Cabelo/metabolismo , Humanos , Melanossomas/metabolismo , Microscopia Eletrônica de Transmissão , Pessoa de Meia-Idade , Adulto Jovem
12.
Int J Mol Sci ; 19(1)2018 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-29315221

RESUMO

Since their invention in 2006, induced Pluripotent Stem (iPS) cells remain a great promise for regenerative medicine circumventing the ethical issues linked to Embryonic Stem (ES) cell research. iPS cells can be generated in a patient-specific manner as an unlimited source of various cell types for in vitro drug screening, developmental biology studies and regenerative use. Having the capacity of differentiating into the cells of all three primary germ layers, iPS cells have high potential to form teratoma tumors. This remains their main disadvantage and hazard which, until resolved, prevents utilization of iPS cells in clinic. Here, we present an approach for increasing iPS cells safety by introducing genetic modification-exogenous suicide gene Herpes Simplex Virus Thymidine Kinase (HSV-TK). Its expression results in specific vulnerability of genetically modified cells to prodrug-ganciclovir (GCV). We show that HSV-TK expressing cells can be eradicated both in vitro and in vivo with high specificity and efficiency with low doses of GCV. Described strategy increases iPS cells safety for future clinical applications by generating "emergency exit" switch allowing eradication of transplanted cells in case of their malfunction.


Assuntos
Simplexvirus/genética , Timidina Quinase/metabolismo , Proteínas Virais/metabolismo , Animais , Apoptose , Reprogramação Celular , Feminino , Ganciclovir/farmacologia , Expressão Gênica/efeitos dos fármacos , Genes Transgênicos Suicidas/genética , Cabelo/citologia , Humanos , Células-Tronco Pluripotentes Induzidas/citologia , Células-Tronco Pluripotentes Induzidas/efeitos dos fármacos , Células-Tronco Pluripotentes Induzidas/metabolismo , Queratinócitos/citologia , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Neoplasias/patologia , Neoplasias/terapia , Simplexvirus/enzimologia , Teratoma/patologia , Timidina Quinase/genética , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Proteínas Virais/genética
13.
Curr HIV/AIDS Rep ; 15(1): 49-59, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29380227

RESUMO

PURPOSE OF REVIEW: In this review, we present new developments in antiretroviral adherence, focusing on pharmacological measures and real-time adherence monitoring. In addition, new strategies on how to incorporate these new measures into research and clinical care are proposed. RECENT FINDINGS: Antiretroviral drug concentrations in hair and dried blood spots are two novel pharmacological measures of cumulative drug adherence and exposure that have been recently evaluated in HIV treatment and pre-exposure prophylaxis. Real-time adherence monitoring using electronic devices has also proven highly informative, feasible, and well accepted, offering the possibility for an immediate intervention when non-adherence is detected. Both approaches offer considerable advantages over traditional adherence measures in predicting efficacy. New methods to objectively monitor adherence in real-time and over long time periods have been developed. Further research is required to better understand how these measures can optimize adherence and, ultimately, improve clinical outcomes in HIV treatment and prevention.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Antirretrovirais/uso terapêutico , Infecções por HIV/tratamento farmacológico , Adesão à Medicação/psicologia , Profilaxia Pré-Exposição/métodos , HIV/efeitos dos fármacos , Cabelo/citologia , Humanos
14.
Sci Rep ; 8(1): 393, 2018 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-29321681

RESUMO

Hair growth occurs periodically in a cycle that consists of three different phases: growth, regression, and resting. The length of each phase is regulated by both intrinsic and extrinsic factors throughout life, and influenced by physiological and pathological conditions. Elongation of the resting phase and shortening of the growth phase occur during physiological ageing and in baldness, respectively. In vivo discrimination of each phase of the hair cycle can be used to research for regeneration of hair follicles as well as to evaluate the efficacy of hair regrowth treatments in the same individual. Here we show that NG2+ epithelial cells in the hair follicles encompass bulge stem cells, and that the number of hair follicle NG2 cells underwent dramatic changes during the hair cycle. Transgenic rats with expression of firefly luciferase gene in NG2 cells were generated to monitor the hair cycle in vivo. Hair follicle NG2 cells were clearly visualized via bioluminescence imaging to study each phase of the hair cycle in the rats, from infancy to old age.


Assuntos
Antígenos/metabolismo , Folículo Piloso/metabolismo , Cabelo/crescimento & desenvolvimento , Medições Luminescentes/métodos , Proteoglicanas/metabolismo , Animais , Antígenos/genética , Proliferação de Células , Feminino , Cabelo/citologia , Cabelo/metabolismo , Folículo Piloso/citologia , Masculino , Proteoglicanas/genética , Ratos , Ratos Transgênicos
15.
Br J Dermatol ; 178(6): 1341-1352, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29181849

RESUMO

BACKGROUND: Transition of hair shaft keratinocytes from actively respiring, nucleated cells to structural cells devoid of nucleus and cytoplasm is key to hair production. This form of cell 'death', or cornification, requires cellular organelle removal to allow the cytoplasm to become packed with keratin filament bundles that further require cross-linking to create a strong hair fibre. Although these processes are well described in epidermal keratinocytes, there is a lack of understanding of such mechanisms, specifically in the hair follicle. OBJECTIVES: To gain insights into cornification mechanisms within the hair follicle and thus improve our understanding of normal hair physiology. METHODS: Scalp biopsies and hair-pluck samples were obtained from healthy human donors and analysed microscopically after immunohistochemical staining. RESULTS: A focal point of respiratory activity was evident in keratogenous zone cells within the hair shaft, which also exhibited nuclear damage. Nuclear degradation occurred via both caspase-dependent and caspase-independent pathways. Conversely, mitophagy was driven by Bnip3L and restricted to the boundary of the keratogenous zone at Adamson's Fringe. CONCLUSIONS: We propose a model of stepwise living-dead transition within the first 1 mm of hair formation, whereby fully functional, nucleated cells first consolidate required functions by degrading nuclear DNA, yet continue to respire and provide the source of reactive oxygen species required for keratin cross-linking. Finally, as the cells become packed with keratin bundles, Bnip3L expression triggers mitophagy to rid the cells of the last remaining 'living' characteristic, thus completing the march from 'living' to 'dead' within the hair follicle.


Assuntos
Cabelo/crescimento & desenvolvimento , Queratinócitos/citologia , Organelas/ultraestrutura , Adolescente , Adulto , Idoso , Apoptose/fisiologia , Autofagia/fisiologia , Morte Celular/fisiologia , Diferenciação Celular , Núcleo Celular/ultraestrutura , Reagentes para Ligações Cruzadas/metabolismo , Feminino , Cabelo/citologia , Cabelo/ultraestrutura , Folículo Piloso/citologia , Folículo Piloso/crescimento & desenvolvimento , Folículo Piloso/ultraestrutura , Voluntários Saudáveis , Humanos , Queratinócitos/ultraestrutura , Queratinas/metabolismo , Microscopia Confocal , Microscopia Eletrônica de Transmissão , Pessoa de Meia-Idade , Mitocôndrias/ultraestrutura , Oxirredução , Estresse Oxidativo/fisiologia , Couro Cabeludo/citologia , Couro Cabeludo/crescimento & desenvolvimento , Couro Cabeludo/ultraestrutura , Adulto Jovem
16.
Exp Dermatol ; 27(3): 292-294, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29105165

RESUMO

A deconvolution process has been developed for curves obtained by differential scanning calorimetry in water for Merino wool and the main ethnic hair types. This enables estimation of the fractions of ortho- and para-type cell groups. The results also indicate that hair may contain a further, low-sulphur subgroup of ortho-type cells. The sizes of the major cell fractions are in line with expectations from microscopical investigations. The fractions are comparable for hair types, and no consistent association between cell-type fractions and hair curvature is observed.


Assuntos
Grupo com Ancestrais do Continente Africano , Grupo com Ancestrais do Continente Asiático , Grupo com Ancestrais do Continente Europeu , Cabelo/química , Cabelo/citologia , Animais , Varredura Diferencial de Calorimetria , Cabelo/anatomia & histologia , Humanos , Microscopia Eletrônica de Transmissão , Ovinos , Enxofre/análise , Lã/citologia
17.
PLoS Biol ; 15(12): e2004412, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-29261650

RESUMO

Sixty-five years after Turing first revealed the potential of systems with local activation and long-range inhibition to generate pattern, we have only recently begun to identify the biological elements that operate at many scales to generate periodic patterns in nature. In this Primer, we first review the theoretical framework provided by Turing, Meinhardt, and others that suggests how periodic patterns could self-organize in developing animals. This Primer was developed to provide context for recent studies that reveal how diverse molecular, cellular, and physical mechanisms contribute to the establishment of the periodic pattern of hair or feather buds in the developing skin. From an initial emphasis on trying to disambiguate which specific mechanism plays a primary role in hair or feather bud development, we are beginning to discover that multiple mechanisms may, in at least some contexts, operate together. While the emergence of the diverse mechanisms underlying pattern formation in specific biological contexts probably reflects the contingencies of evolutionary history, an intriguing possibility is that these mechanisms interact and reinforce each other, producing emergent systems that are more robust.


Assuntos
Padronização Corporal/fisiologia , Plumas/citologia , Cabelo/citologia , Modelos Biológicos , Animais , Plumas/anatomia & histologia , Plumas/crescimento & desenvolvimento , Cabelo/anatomia & histologia , Cabelo/crescimento & desenvolvimento , Transdução de Sinais , Pele/anatomia & histologia , Pele/citologia , Pele/crescimento & desenvolvimento
18.
Biotechniques ; 63(3): 131-134, 2017 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-28911317

RESUMO

Biological evaluation of hair growth/differentiation activity in vitro has been a formidable challenge, primarily due to the lack of relevant model cell systems. To solve this problem, we generated a stable model cell line in which successive differentiation via epidermal progenitors to hair components is easily inducible and traceable. Mouse induced pluripotent stem (iPS) cell-derived cells were selected to stably express a tetracycline (Tet)-inducible bone morphogenic protein-4 (BMP4) expression cassette and a luciferase reporter driven by a hair-specific keratin 31 gene (krt31) promoter (Tet-BMP4-KRT31-Luc iPS). While Tet- BMP4-KRT31-Luc iPS cells could be maintained as stable iPS cells, the cells differentiated to produce luciferase luminescence in the presence of all-trans retinoic acid (RA) and doxycycline (Dox), and addition of a hair differentiation factor significantly increased luciferase fluorescence. Thus, this cell line may provide a reliable cell-based screening system to evaluate drug candidates for hair differentiation activity.


Assuntos
Alopecia/terapia , Diferenciação Celular , Engenharia Celular/métodos , Cabelo/citologia , Cabelo/crescimento & desenvolvimento , Células-Tronco Pluripotentes Induzidas/citologia , Animais , Proteína Morfogenética Óssea 4/genética , Proteína Morfogenética Óssea 4/metabolismo , Linhagem Celular , Doxiciclina/farmacologia , Avaliação Pré-Clínica de Medicamentos , Células-Tronco Pluripotentes Induzidas/metabolismo , Queratinas Específicas do Cabelo/genética , Queratinas Específicas do Cabelo/metabolismo , Queratinas Tipo I/genética , Queratinas Tipo I/metabolismo , Luciferases/metabolismo , Substâncias Luminescentes/metabolismo , Camundongos , Regiões Promotoras Genéticas , Tetraciclina/farmacologia , Tretinoína/farmacologia
19.
Curr Stem Cell Res Ther ; 12(7): 535-543, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28875863

RESUMO

BACKGROUND: Adipose-derived stem cells (ADSCs) are mesenchymal stem cells (MSCs) within the stromal vascular fraction of subcutaneous adipose tissue. ADSCs secrete growth factors and other proteins, and have been used to regenerate skin with satisfactory results. OBJECTIVE: This review focuses on the effect of ADSCs and their secretory factors on the stimulation of hair growth in vitro, ex vivo and in vivo. RESULTS: The conditioned media of ADSCs (ADSC-CM) increases the proliferation rate of human follicular cells. ADSCs-derived proteins improve hair growth and protect human dermal papilla cells against cytotoxic injury caused by androgen and reactive oxygen species. Moreover, ADSC-CM induces the anagen phase and promotes hair growth in mice, and enhances the elongation of hair shafts in ex vivo human hair organ cultures. CONCLUSION: ADSC-CM promotes hair growth in vitro, ex vivo, and in vivo. Given that ADSCs are one of the most accessible sources of MSCs, ADSC-derived proteins may be feasible clinical therapeutic agents for the treatment of hair loss.


Assuntos
Tecido Adiposo/citologia , Alopecia/terapia , Meios de Cultivo Condicionados/farmacologia , Cabelo/citologia , Cabelo/fisiologia , Células-Tronco Mesenquimais/citologia , Regeneração , Tecido Adiposo/metabolismo , Animais , Citocinas/farmacologia , Humanos , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/metabolismo
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