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Sample records for skin hair follicles

  1. In-vitro and in-vivo study of dye diffusion into the human skin and hair follicles

    NASA Astrophysics Data System (ADS)

    Genina, Elina A.; Bashkatov, Alexey N.; Sinichkin, Yurii P.; Kochubey, Vyacheslav I.; Lakodina, Nina A.; Perpelitzina, Olga A.; Altshuler, Gregory B.; Tuchin, Valery V.

    2000-11-01

    We present experimental results on in vitro and in vivo investigation of dye diffusion into the human skin and hair follicles. It was shown that dyeing as a method of enhancement of the absorption coefficient of hair follicle tissue components can be used for selective photodestruction of hair follicle and surrounding tissues. Strength and depth of hair follicle dyeing inside the skin were determined for various dyes.

  2. Epidermal stem cells and skin tissue engineering in hair follicle regeneration

    PubMed Central

    Balañá, María Eugenia; Charreau, Hernán Eduardo; Leirós, Gustavo José

    2015-01-01

    The reconstitution of a fully organized and functional hair follicle from dissociated cells propagated under defined tissue culture conditions is a challenge still pending in tissue engineering. The loss of hair follicles caused by injuries or pathologies such as alopecia not only affects the patients’ psychological well-being, but also endangers certain inherent functions of the skin. It is then of great interest to find different strategies aiming to regenerate or neogenerate the hair follicle under conditions proper of an adult individual. Based upon current knowledge on the epithelial and dermal cells and their interactions during the embryonic hair generation and adult hair cycling, many researchers have tried to obtain mature hair follicles using different strategies and approaches depending on the causes of hair loss. This review summarizes current advances in the different experimental strategies to regenerate or neogenerate hair follicles, with emphasis on those involving neogenesis of hair follicles in adult individuals using isolated cells and tissue engineering. Most of these experiments were performed using rodent cells, particularly from embryonic or newborn origin. However, no successful strategy to generate human hair follicles from adult cells has yet been reported. This review identifies several issues that should be considered to achieve this objective. Perhaps the most important challenge is to provide three-dimensional culture conditions mimicking the structure of living tissue. Improving culture conditions that allow the expansion of specific cells while protecting their inductive properties, as well as methods for selecting populations of epithelial stem cells, should give us the necessary tools to overcome the difficulties that constrain human hair follicle neogenesis. An analysis of patent trends shows that the number of patent applications aimed at hair follicle regeneration and neogenesis has been increasing during the last decade. This

  3. Hair Follicle Regeneration in Skin Grafts: Current Concepts and Future Perspectives

    PubMed Central

    Mahjour, Seyed Babak; Ghaffarpasand, Fariborz

    2012-01-01

    The repair and management of full-thickness skin defects resulting from burns and chronic wounds remain a significant unmet clinical challenge. For those skin defects exceeding 50%–60% of total body surface area, it is impractical to treat with autologous skin transplants because of the shortage of donor sites. The possibility of using tissue-engineered skin grafts for full-thickness wound repair is a promising approach. The primary goal of tissue-engineered skin grafts is to restore lost barrier function, but regeneration of appendages, such as hair follicles, has to be yet achieved. The successful regeneration of hair follicles in immunodeficient mice suggests that creating human hair follicles in tissue-engineered skin grafts is feasible. However, many limitations still need to be explored, particularly enriching isolated cells with trichogenic capacity, maintaining this ability during processing, and providing the cells with proper environmental cues. Current advances in hair follicle regeneration, in vitro and in vivo, are concisely summarized in this report, and key requirements to bioengineer a hair follicle are proposed, with emphasis on a three-dimensional approach. PMID:21883016

  4. In vitro and in vivo study of dye diffusion into the human skin and hair follicles.

    PubMed

    Genina, Elina A; Bashkatov, Alexey N; Sinichkin, Yury P; Kochubey, Vyacheslav I; Lakodina, Nina A; Altshuler, Gregory B; Tuchin, Valery V

    2002-07-01

    We present experimental results on the in vitro and in vivo study of dye diffusion into human skin and hair follicles. We have studied some commercially available dyes for potential using in the laser selective thermolysis. The degree and the depth of hair follicle dyeing inside the skin were determined. For hairs in different stages the sebaceous gland was stated as a reservoir for a dye administration. It was found that the penetration depth of dyes is about 1.2 mm from the skin surface. We have developed the biocompatible Indocyanine Green lotions and the method for in vivo dyeing and dye in depth monitoring. Shift on 16-21 nm of absorption peak of Indocyanine Green to the longer wavelengths due to Indocyanine Green binding with cell proteins in the human skin was found.

  5. Promotion of hair follicle development and trichogenesis by Wnt-10b in cultured embryonic skin and in reconstituted skin

    SciTech Connect

    Ouji, Yukiteru . E-mail: oujix@naramed-u.ac.jp; Yoshikawa, Masahide; Shiroi, Akira; Ishizaka, Shigeaki

    2006-06-30

    We previously showed that Wnt-10b promoted the differentiation of primary skin epithelial cells (MPSEC) toward hair shaft and inner root sheath of the hair follicle (IRS) cells in vitro. In the present study, we found that Wnt-10b promotes the development of hair follicles using a culture of mouse embryonic skin tissue and trichogenesis using a reconstitution experiment with nude mice. Hair follicle development was observed in skin taken from mouse embryos on embryonic day 10.5 following a 2-day culture with recombinant Wnt-10b (rWnt-10b), however, not without rWnt-10b. Brown hair growth was observed at the site of reconstituted skin in Balb/c nude mice where dermal fibroblasts and keratinocytes, derived from C3H/HeN new born mice, were transplanted with Wnt-10b-producing COS cells (Wnt-COS). Without the co-transplantation of Wnt-COS, no hair growth was observed. Our results suggest an important role of Wnt-10b in the initiation of hair follicle development and following trichogenesis.

  6. Bioengineering the Hair Follicle

    PubMed Central

    Parimoo, S; Zheng, Y; Barrows, T; Boucher, M; Washenik, K

    2007-01-01

    The hair follicle develops from the primitive embryonic epidermis as a result of complex epithelial-mesenchymal interactions. The full follicle, consisting of epithelial cylinders under control of a proximal lying mesenchymal papilla, grows in cycles giving rise to a new hair shaft during each cycle. The ability to cycle endows the follicle with regenerative properties. The evolution of hair follicle engineering began with the recognition in the early 1960's that hair follicles could be transplanted clinically into a foreign site and still grow a shaft typical of the donor site. Since that time, it has been found that the follicular papilla has hair follicle inducing properties and that the hair follicle houses within it epithelial stem cells that can respond to hair inductive signals. These findings have laid the foundation for isolating hair-forming cells, for expanding the cells in culture, and for forming new follicles in vivo. PMID:19279694

  7. Micro-RNA-31 controls hair cycle-associated changes in gene expression programs of the skin and hair follicle.

    PubMed

    Mardaryev, Andrei N; Ahmed, Mohammed I; Vlahov, Nikola V; Fessing, Michael Y; Gill, Jason H; Sharov, Andrey A; Botchkareva, Natalia V

    2010-10-01

    The hair follicle is a cyclic biological system that progresses through stages of growth, regression, and quiescence, which involves dynamic changes in a program of gene regulation. Micro-RNAs (miRNAs) are critically important for the control of gene expression and silencing. Here, we show that global miRNA expression in the skin markedly changes during distinct stages of the hair cycle in mice. Furthermore, we show that expression of miR-31 markedly increases during anagen and decreases during catagen and telogen. Administration of antisense miR-31 inhibitor into mouse skin during the early- and midanagen phases of the hair cycle results in accelerated anagen development, and altered differentiation of hair matrix keratinocytes and hair shaft formation. Microarray, qRT-PCR and Western blot analyses revealed that miR-31 negatively regulates expression of Fgf10, the components of Wnt and BMP signaling pathways Sclerostin and BAMBI, and Dlx3 transcription factor, as well as selected keratin genes, both in vitro and in vivo. Using luciferase reporter assay, we show that Krt16, Krt17, Dlx3, and Fgf10 serve as direct miR-31 targets. Thus, by targeting a number of growth regulatory molecules and cytoskeletal proteins, miR-31 is involved in establishing an optimal balance of gene expression in the hair follicle required for its proper growth and hair fiber formation.

  8. In vitro skin models to study epithelial regeneration from the hair follicle

    PubMed Central

    Ojeh, Nkemcho; Akgül, Baki; Tomic-Canic, Marjana; Philpott, Mike

    2017-01-01

    The development of dermal equivalents (DEs) for the treatment of burns has contributed toward efficient wound closure. A collagen-glycosaminoglycan DE (C-GAG) grafted with hair follicles converted a full-thickness wound to partial-thickness resulting in complete wound closure and restored hair. In this study we compared the ability of both intact pilosebaceous units (PSU) or truncated hair follicles (THF) to regenerate a multilayered epidermis in vitro when implanted into de-epidermalized dermis (DED) or C-GAG with the epidermis generated in vivo using C-CAG. Keratinocytes explanted from the outer root sheath of PSU and THF in both DED and C-GAG but only formed a multilayered epidermis with PSU in DED. PSU were more effective at forming multilayered epidermis in DED than THF. Both DED and C-GAG skin expressed proliferation (PCNA), differentiation (K1, K10), hyperproliferation (K6, K16), basal (K14), putative stem cell (p63), extracellular matrix protein (Collagen IV), mesenchymal (vimentin) and adherens junction (β-catenin) markers. These data suggest DEs supported initial maintenance of the implanted hair follicles, in particular PSU, and provide an excellent model with which to investigate the regulation of hair follicle progenitor epithelial cells during epidermal regeneration. Although neither PSU nor THF formed multilayered epidermis in C-CAG in vitro, hair follicles implanted into engrafted C-GAG on a burns patient resulted in epithelial regeneration and expression of proliferation and differentiation markers in a similar manner to that seen in vitro. However, the failure of C-GAG to support epidermal regeneration in vitro suggests in vivo factors are essential for full epidermal regeneration using C-GAG. PMID:28350869

  9. Skin, Hair, and Nails

    MedlinePlus

    ... thousands of cells and hundreds of sweat glands, oil glands, nerve endings, and blood vessels. Skin is ... empty into hair follicles and pores, produce the oil sebum that lubricates the skin and hair. Sebaceous ...

  10. Hair follicle-derived blood vessels vascularize tumors in skin and are inhibited by Doxorubicin.

    PubMed

    Amoh, Yasuyuki; Li, Lingna; Yang, Meng; Jiang, Ping; Moossa, Abdool R; Katsuoka, Kensei; Hoffman, Robert M

    2005-03-15

    We have recently shown that the neural-stem cell marker nestin is expressed in hair follicle stem cells and the blood vessel network interconnecting hair follicles in the skin of transgenic mice with nestin regulatory element-driven green fluorescent protein (ND-GFP). The hair follicles were shown to give rise to the nestin-expressing blood vessels in the skin. In the present study, we visualized tumor angiogenesis by dual-color fluorescence imaging in ND-GFP transgenic mice after transplantation of the murine melanoma cell line B16F10 expressing red fluorescent protein. ND-GFP was highly expressed in proliferating endothelial cells and nascent blood vessels in the growing tumor. Results of immunohistochemical staining showed that the blood vessel-specific antigen CD31 was expressed in ND-GFP-expressing nascent blood vessels. ND-GFP expression was diminished in the vessels with increased blood flow. Progressive angiogenesis during tumor growth was readily visualized during tumor growth by GFP expression. Doxorubicin inhibited the nascent tumor angiogenesis as well as tumor growth in the ND-GFP mice transplanted with B16F10-RFP. This model is useful for direct visualization of tumor angiogenesis and evaluation of angiogenic inhibitors.

  11. Hair follicle-derived IL-7 and IL-15 mediate skin-resident memory T cell homeostasis and lymphoma

    PubMed Central

    Adachi, Takeya; Kobayashi, Tetsuro; Sugihara, Eiji; Yamada, Taketo; Ikuta, Koichi; Pittaluga, Stefania; Saya, Hideyuki; Amagai, Masayuki; Nagao, Keisuke

    2015-01-01

    The skin harbors a variety of resident leukocyte subsets that must be tightly regulated to maintain immune homeostasis. Hair follicles are unique structures in the skin that contribute to skin dendritic cell homeostasis via chemokine production. We demonstrate that CD4+ and CD8+ skin resident memory T cells (TRM), responsible for long-term skin immunity, resided predominantly within the hair follicle epithelium of unperturbed epidermis. TRM tropism for the epidermis and follicles was herein termed epidermotropism. Hair follicle-derived IL-15 was required for CD8+ TRM, and IL-7 for CD8+ and CD4+ TRM, to exert epidermotropism. The lack of either cytokine impaired hapten-induced contact hypersensitivity responses. In a model of cutaneous T cell lymphoma, epidermotropic CD4+ TRM lymphoma cell localization depended on hair follicle-derived IL-7. These findings implicate hair follicle-derived cytokines as regulators of malignant and non-malignant TRM cell tissue residence and suggest they may be targeted therapeutically in inflammatory skin disease and lymphoma. PMID:26479922

  12. The Hair Follicle Enigma.

    PubMed

    Bernard, Bruno A

    2017-03-07

    The hair follicle is a mini organ endowed with a unique structure and cyclic behavior. Despite the intense research efforts which have been devoted at deciphering the hair follicle biology over the past 70 years, one must admit that hair follicle remains an enigma. In this brief review, various aspects of hair follicle biology will be addressed, and more importantly, unsolved questions and new possible research tracks will be highlighted, including hair follicle glycobiology and exosome mediated cell-cell interactions. Even though bricks of knowledge are solidly being acquired, an integrative picture remains to emerge. One can predict that computer science, algorithms and bioinformatics will assist in fostering our understanding hair biology. This article is protected by copyright. All rights reserved.

  13. Permeant lipophilicity and vehicle composition influence accumulation of dyes in hair follicles of human skin.

    PubMed

    Grams, Ylva Y; Alaruikka, Soile; Lashley, Lisa; Caussin, Julia; Whitehead, Lynne; Bouwstra, Joke A

    2003-04-01

    In skin and hair research drug targeting to the hair follicle is of great interest. Therefore the influence of permeant lipophilicity and vehicle composition on local accumulation has been examined using confocal laser scanning microscopy (CLSM). Formulations saturated with either Oregon Green 488, Bodipy FL C(5) or Bodipy 564/570 C(5) were prepared. The dyes were applied in citric acid buffer, 8% (w/v) surfactants in citric acid buffer or 8% (w/v) surfactants/20% (w/v) propylene glycol in citric acid buffer. Flow-through diffusion experiments were performed with fresh human scalp skin, after which the skin was imaged using CLSM. Diffusion studies showed for Oregon Green 488 (low lipophilicity) a higher flux when applied in citric acid buffer compared to surfactants. In contrast the fluxes of the more lipophilic dyes (Bodipy FL C(5) and Bodipy 564/570 C(5)) are highest when applied in surfactants/propylene glycol. CLSM studies revealed that follicular accumulation increased with (i) a lipophilic dye and (ii) application of lipophilic dyes in surfactants-propylene glycol. Therefore we conclude that targeting to the hair follicle can be increased by the use of lipophilic drugs in combination with surfactant solutions and propylene glycol.

  14. [Cultivated human hair follicle cells are capable of integrating to skin structure in vivo].

    PubMed

    Cheremnykh, E S; Radiukhina, N V; Rutkevich, P N; Shevelev, A Ia; Vlasik, T N; Voroteliak, E A; Vasil'ev, A V; Terskikh, V V

    2010-01-01

    In the present study, human keratinocytes and dermal papilla cells were labeled to investigate their behaviour after intradermal transplantation. Cells were transduced by lentiviral vectors that bore marker gene encoding green fluorescent protein (copGFP) or red fluorescent protein (DsRed). A portion of transgene expressing cells was evaluated by flow cytometry. Genetic constructions that we used provided high level (> 95 %) of transduction of hair follicle cells. In vitro transduced cells were injected under the epidermis of human skin fragments, and these fragments were then transplanted under the skin of immunodeficient mice. Injected epidermal keratinocytes were found, mainly, in hair follicles and partially in a zone of interfollicular epidermis, while dermal papilla cells were found in papilla derma. The results of the present research show that the chosen genetic constructions obtained on a basis of human immunodeficiency lentivirs are capable of effective and stable transduction of human skin cells. Injected cells survived and were found in the corresponding structures of the skin.

  15. Analysis of the expression pattern of the carrier protein transthyretin and its receptor megalin in the human scalp skin and hair follicles: hair cycle-associated changes.

    PubMed

    Adly, Mohamed A

    2010-12-01

    Transthyretin is a serum and cerebrospinal fluid protein synthesized early in development by the liver, choroid plexus and several other tissues. It is a carrier protein for the antioxidant vitamins, retinol, and thyroid hormones. Transthyretin helps internalize thyroxine and retinol-binding protein into cells by binding to megalin, which is a multi-ligand receptor expressed on the luminal surface of various epithelia. We investigated the expression of transthyretin and its receptor megalin in the human skin; however, their expression pattern in the hair follicle is still to be elucidated. This study addresses this issue and tests the hypothesis that "the expression of transthyretin and megalin undergoes hair follicle cycle-dependent changes." A total of 50 normal human scalp skin biopsies were examined (healthy females, 53-62 years) using immunofluorescence staining methods and real-time PCR. In each case, 50 hair follicles were analyzed (35, 10, and 5 follicles in anagen, catagen, and telogen, respectively). Transthyretin and megalin were prominently expressed in the human scalp skin and hair follicles, on both gene and protein levels. The concentrations of transthyretin and megalin were 0.12 and 0.03 Ul/ml, respectively, as indicated by PCR. The expression showed hair follicle cycle-associated changes i.e., strong expression during early and mature anagen, very weak expression during catagen and moderate expression during telogen. The expression values of these proteins in the anagen were statistically significantly higher than those of either catagen or telogen hair follicles (P ≤ 0.001). This study provides the first morphologic indication that transthyretin and megalin are variably expressed in the human scalp skin and hair follicles. It also reports variations in the expression of these proteins during hair follicle cycling. The clinical ramifications of these findings are open for further investigations.

  16. Chromatographic method for clobetasol propionate determination in hair follicles and in different skin layers.

    PubMed

    Ângelo, Tamara; Cunha-Filho, Marcílio S S; Gelfuso, Guilherme M; Gratieri, Tais

    2017-02-01

    Clobetasol propionate (CLO) is a potent steroid used for the treatment of several dermatological diseases. Recent studies suggest its additional use in alopecia topical treatment, generating a demand for novel formulations with specific delivery into hair follicles. Hence, a selective analytical method for drug quantification in follicular structures and skin layers is required. For this, a simple HPLC-UV method was developed. Quantification was performed using a RP-C18 column (4.6 mm × 15 cm, 5 μm), with a mixture of methanol-acetonitrile-water (50:15:35 v/v) as mobile phase, a flow rate of 1.2 mL/min, oven temperature of 30°C, injection volume of 50 μL and detection at 240 nm. The optimized conditions enabled a 12 min running with CLO elution at 10.1 min and resolution of 2.424 from skin matrix interferences. Validation was performed in accordance with International Conference on Harmonization guidelines and fulfilled the criteria of selectivity, linearity (0.5-15.0 μg/mL), robustness, precision, accuracy and limits of detection and quantification (0.02 and 0.07 μg/mL, respectively). The validated method was successfully applied for CLO quantification following in vitro skin permeation experiments and differential tape-stripping for hair follicle deposition determination, demonstrating its suitability.

  17. Reflectance spectroscopy for evaluating hair follicle cycle

    NASA Astrophysics Data System (ADS)

    Liu, Caihua; Guan, Yue; Wang, Jianru; Zhu, Dan

    2014-02-01

    Hair follicle, as a mini-organ with perpetually cycling of telogen, anagen and catagen, provides a valuable experimental model for studying hair and organ regeneration. The transition of hair follicle from telogen to anagen is a significant sign for successful regeneration. So far discrimination of the hair follicle stage is mostly based on canonical histological examination and empirical speculation based on skin color. Hardly a method has been proposed to quantitatively evaluate the hair follicle stage. In this work, a commercial optical fiber spectrometer was applied to monitor diffuse reflectance of mouse skin with hair follicle cycling, and then the change of reflectance was obtained. Histological examination was used to verify the hair follicle stage. In comparison with the histological examination, the skin diffuse reflectance was relatively high for mouse with telogen hair follicles; it decreased once hair follicles transited to anagen stage; then it increased reversely at catagen stage. This study provided a new method to quantitatively evaluate the hair follicle stage, and should be valuable for the basic and therapeutic investigations on hair regeneration.

  18. Use of the skin sandwich technique to probe the role of the hair follicles in sonophoresis.

    PubMed

    Sarheed, Omar; Frum, Yakov

    2012-02-28

    The human skin sandwich technique was used to explore the effect of brief ultrasound exposure on the transfollicular pathway of absorption. Hydrocortisone was used as a model drug. In order to calculate the permeability coefficient of hydrocortisone, its concentration at saturation in the PBS donor solution was determined. Skin samples were prepared by sandwich technique with total hydration of the epidermal and sandwich membranes. The skin was sonicated for 0 s (control), 30 s or 45 s using a pulsed mode (10% duty cycle) with the spatial and temporal average intensity (SATA) of 3.7 W/cm(2). The transducer was then removed and permeation was allowed to proceed for 52 h. Then the percentage follicular contribution was determined. It was determined that without ultrasound, drug entry into follicles accounted for 46% of total penetration. As the duration of sonication increased, the follicular contribution fell to zero even though total transepidermal flux dramatically increased. This is explained by ultrasound exposure causing sloughing off of the uppermost stratum corneum. This permeabilises the continuous surface but at the same time the disturbed cornceocytes will plug hair follicle orifices.

  19. Ion beam microanalysis of human hair follicles

    NASA Astrophysics Data System (ADS)

    Kertész, Zs.; Szikszai, Z.; Pelicon, P.; Simčič, J.; Telek, A.; Bíró, T.

    2007-07-01

    Hair follicle is an appendage organ of the skin which is of importance to the survival of mammals and still maintains significance for the human race - not just biologically, but also through cosmetic and commercial considerations. However data on composition of hair follicles are scarce and mostly limited to the hair shaft. In this study we provide detailed information on the elemental distribution in human hair follicles in different growth phases (anagen and catagen) using a scanning proton microprobe. The analysis of skin samples obtained from human adults undergoing plastic surgery and of organ-cultured human hair follicles may yield a new insight into the function, development and cyclic activity of the hair follicle.

  20. Discrimination between basal cell carcinoma and hair follicles in skin tissue sections by Raman micro-spectroscopy

    NASA Astrophysics Data System (ADS)

    Larraona-Puy, M.; Ghita, A.; Zoladek, A.; Perkins, W.; Varma, S.; Leach, I. H.; Koloydenko, A. A.; Williams, H.; Notingher, I.

    2011-05-01

    Skin cancer is the most common human malignancy and basal cell carcinoma (BCC) represents approximately 80% of the non-melanoma cases. Current methods of treatment require histopathological evaluation of the tissues by qualified personnel. However, this method is subjective and in some cases BCC can be confused with other structures in healthy skin, including hair follicles. In this preliminary study, we investigated the potential of Raman micro-spectroscopy (RMS) to discriminate between hair follicles and BCC in skin tissue sections excised during Mohs micrographic surgery (MMS). Imaging and diagnosis of skin sections was automatically generated using ' a priori'-built spectral model based on LDA. This model had 90 ± 9% sensitivity and 85 ± 9% specificity for discrimination of BCC from dermis and epidermis. The model used selected Raman bands corresponding to the largest spectral differences between the Raman spectra of BCC and the normal skin regions, associated mainly with nucleic acids and collagen type I. Raman spectra corresponding to the epidermis regions of the hair follicles were found to be closer to those of healthy epidermis rather than BCC. Comparison between Raman spectral images and the gold standard haematoxylin and eosin (H&E) histopathology diagnosis showed good agreement. Some hair follicle regions were misclassified as BCC; regions corresponded mainly to the outermost layer of hair follicle (basal cells) which are expected to have higher nucleic acid concentration. This preliminary study shows the ability of RMS to distinguish between BCC and other tissue structures associated to healthy skin which can be confused with BCC due to their similar morphology.

  1. Penetration and distribution of three lipophilic probes in vitro in human skin focusing on the hair follicle.

    PubMed

    Grams, Ylva Y; Bouwstra, Joke A

    2002-10-04

    Fluorescent model substances of increasing lipophilicity (Oregon Green) 488, Bodipy, FL C5 and Bodipy 564/570 C5) were selected to enable the visualization in the skin using confocal laser scanning microscopy. After measuring the penetration for 18 h, the nonfixed human scalp skin was imaged from the bottom parallel to the stratum corneum and in a cross-section view perpendicular to the skin surface. The images were evaluated by calculating relative accumulation values for different penetrants. The studies indicate that the penetrated amount is highest for Bodipy FL C5 (medium lipophilicity) and lowest for Bodipy 564/570 C5 (high lipophilicity) whereas Bodipy 564/570 C5 (high lipophilicity) reveals the highest relative accumulation in parts of the hair follicle compared to Oregon Green 488 (low lipophilicity). The addition of 30% (v/v) ethanol to the donor phase of substance with a low lipophilicity increases the follicular delivery. From our results we conclude that delivery to the hair follicle can be improved by increasing the drugs lipophilicity and optimizing the composition of the donor phase. However, no conclusion can be drawn about the actual route of transport to the hair follicle.

  2. Corneodesmosin gene ablation induces lethal skin-barrier disruption and hair-follicle degeneration related to desmosome dysfunction.

    PubMed

    Leclerc, Emilie A; Huchenq, Anne; Mattiuzzo, Nicolas R; Metzger, Daniel; Chambon, Pierre; Ghyselinck, Norbert B; Serre, Guy; Jonca, Nathalie; Guerrin, Marina

    2009-08-01

    Corneodesmosin (CDSN) is specific to desmosomes of epithelia undergoing cornification, mainly the epidermis and the inner root sheath of the hair follicles. CDSN nonsense mutations are associated with hypotrichosis simplex of the scalp, a rare disease that leads to complete baldness in young adults. CDSN displays adhesive properties, mostly attributable to its N-terminal glycine-rich domain, and is sequentially proteolyzed as corneocytes migrate towards the skin surface. K14-promoter driven Cre-mediated deletion of Cdsn in mice resulted in neonatal death as a result of epidermal tearing upon minor mechanical stress. Ultrastructural analyses revealed a desmosomal break at the interface between the living and cornified layers. After grafting onto nude mice, knockout skin showed a chronic defect in the epidermal permeability barrier. The epidermis was first hyperproliferative with a thick cornified layer, then, both the epidermis and the hair follicles degenerated. In adults, Cdsn deletion resulted in similar histological abnormalities and in a lethal barrier defect. We demonstrate that Cdsn is not essential for skin-barrier formation in utero, but is vital throughout life to preserve this barrier by maintaining desmosome integrity. The strong adhesive function that the protein confers on corneodesmosomes also seems necessary for maintaining the architecture of the hair follicle.

  3. Reflectance spectroscopy for noninvasive evaluation of hair follicle stage

    NASA Astrophysics Data System (ADS)

    Liu, Caihua; Guan, Yue; Wang, Jianru; Zhong, Xiewei; Liu, Xiuli; Zhu, Dan

    2015-05-01

    Hair follicle offers an excellent model for systems biology and regenerative medicine. So far, the stages of hair follicle growth have been evaluated by histological examination. In this work, a noninvasive spectroscopy was proposed by measuring the diffuse reflectance of mouse skin and analyzing the melanin value. Results show that the skin diffuse reflectance was relatively high when hair follicles were at the telogen stage and at the beginning of the anagen stage, and decreased with the progression of the anagen stage. When the hair follicle entered into the catagen stage, the diffuse reflectance gradually increased. The changes in the melanin content of skin had contrary dynamics. Substages of the hair follicle cycle could be distinguished by comparing the changes in melanin value with the histological examination. This study provided a new method for noninvasive evaluation of the hair follicle stage, and should be valuable for basic and therapeutic investigations on hair regeneration.

  4. The hair follicle as a target for gene therapy.

    PubMed

    Gupta, S; Domashenko, A; Cotsarelis, G

    2001-01-01

    The hair follicle possesses progenitor cells for continued hair follicle cycling and for epidermal keratinocytes, melanocytes and Langerhans cells. These different cell types can be targeted by topical gene delivery to mouse skin. Using a combination of liposomes and DNA, we demonstrated the feasibility of targeting hair follicle cells in human scalp xenografts as well. We defined liposome composition and stage of the hair cycle as important parameters influencing transfection of human hair follicles. Transfection occurred only during anagen onset. Considerations and obstacles for using gene therapy to treat alopecias and skin disease are discussed. A theoretical framework for future gene therapy treatments for cutaneous and systemic disorders is presented.

  5. Photoactivation of ROS production in situ transiently activates cell proliferation in mouse skin and in the hair follicle stem cell niche promoting hair growth and wound healing

    PubMed Central

    Carrasco, Elisa; Calvo, María I.; Blázquez-Castro, Alfonso; Vecchio, Daniela; Zamarrón, Alicia; de Almeida, Irma Joyce Dias; Stockert, Juan C.; Hamblin, Michael R.; Juarranz, Ángeles; Espada, Jesús

    2015-01-01

    The role of reactive oxygen species (ROS) in the regulation of hair follicle cycle and skin homeostasis is poorly characterized. ROS have been traditionally linked to human disease and ageing, but recent findings suggest that can also have beneficial physiological functions in vivo in mammals. To test this hypothesis, we transiently switched on in situ ROS production in mouse skin. This process activated cell proliferation in the tissue and, interestingly, in the bulge region of the hair follicle, a major reservoir of epidermal stem cells, promoting hair growth as well as stimulating tissue repair after severe burn injury. We further show that these effects were associated with a transient Src kinase phosphorylation at Tyr416 and with a strong transcriptional activation of the prolactin family 2 subfamily c of growth factors. Our results point to potentially relevant modes of skin homeostasis regulation and demonstrate that a local and transient ROS production can regulate stem cell and tissue function in the whole organism. PMID:26134949

  6. Gene and stem cell therapy of the hair follicle.

    PubMed

    Hoffman, Robert M

    2005-01-01

    The hair follicle is a highly complex appendage of the skin containing a multiplicity of cell types. The follicle undergoes constant cycling through the life of the organism including growth and resorption with growth dependent on specific stem cells. The targeting of the follicle by genes and stem cells to change its properties, in particular, the nature of the hair shaft is discussed. Hair follicle delivery systems are described such as liposomes and viral vectors for gene therapy. The nature of the hair follicle stem cells is discussed, in particular, its pluripotency.

  7. MicroRNA-214 controls skin and hair follicle development by modulating the activity of the Wnt pathway.

    PubMed

    Ahmed, Mohammed I; Alam, Majid; Emelianov, Vladimir U; Poterlowicz, Krzysztof; Patel, Ankit; Sharov, Andrey A; Mardaryev, Andrei N; Botchkareva, Natalia V

    2014-11-24

    Skin development is governed by complex programs of gene activation and silencing, including microRNA-dependent modulation of gene expression. Here, we show that miR-214 regulates skin morphogenesis and hair follicle (HF) cycling by targeting β-catenin, a key component of the Wnt signaling pathway. miR-214 exhibits differential expression patterns in the skin epithelium, and its inducible overexpression in keratinocytes inhibited proliferation, which resulted in formation of fewer HFs with decreased hair bulb size and thinner hair production. The inhibitory effects of miR-214 on HF development and cycling were associated with altered activities of multiple signaling pathways, including decreased expression of key Wnt signaling mediators β-catenin and Lef-1, and were rescued by treatment with pharmacological Wnt activators. Finally, we identify β-catenin as one of the conserved miR-214 targets in keratinocytes. These data provide an important foundation for further analyses of miR-214 as a key regulator of Wnt pathway activity and stem cell functions during normal tissue homeostasis, regeneration, and aging.

  8. Dermal Papilla Cells Improve the Wound Healing Process and Generate Hair Bud-Like Structures in Grafted Skin Substitutes Using Hair Follicle Stem Cells

    PubMed Central

    Leirós, Gustavo José; Kusinsky, Ana Gabriela; Drago, Hugo; Bossi, Silvia; Sturla, Flavio; Castellanos, María Lía; Stella, Inés Yolanda

    2014-01-01

    Tissue-engineered skin represents a useful strategy for the treatment of deep skin injuries and might contribute to the understanding of skin regeneration. The use of dermal papilla cells (DPCs) as a dermal component in a permanent composite skin with human hair follicle stem cells (HFSCs) was evaluated by studying the tissue-engineered skin architecture, stem cell persistence, hair regeneration, and graft-take in nude mice. A porcine acellular dermal matrix was seeded with HFSCs alone and with HFSCs plus human DPCs or dermal fibroblasts (DFs). In vitro, the presence of DPCs induced a more regular and multilayered stratified epidermis with more basal p63-positive cells and invaginations. The DPC-containing constructs more accurately mimicked the skin architecture by properly stratifying the differentiating HFSCs and developing a well-ordered epithelia that contributed to more closely recapitulate an artificial human skin. This acellular dermal matrix previously repopulated in vitro with HFSCs and DFs or DPCs as the dermal component was grafted in nude mice. The presence of DPCs in the composite substitute not only favored early neovascularization, good assimilation and remodeling after grafting but also contributed to the neovascular network maturation, which might reduce the inflammation process, resulting in a better healing process, with less scarring and wound contraction. Interestingly, only DPC-containing constructs showed embryonic hair bud-like structures with cells of human origin, presence of precursor epithelial cells, and expression of a hair differentiation marker. Although preliminary, these findings have demonstrated the importance of the presence of DPCs for proper skin repair. PMID:25161315

  9. Hair follicle growth controls.

    PubMed

    Stenn, K S; Combates, N J; Eilertsen, K J; Gordon, J S; Pardinas, J R; Parimoo, S; Prouty, S M

    1996-10-01

    Research in hair biology has embarked in the pursuit for molecules that control hair growth. Many molecules already have been associated with the controls of hair patterning, hair maturation, and hair cycling and differentiation. Knowing how these molecules work gives us the tools for understanding and treating patients with hair disorders.

  10. Discovery of cashmere goat (Capra hircus) microRNAs in skin and hair follicles by Solexa sequencing

    PubMed Central

    2013-01-01

    Background MicroRNAs (miRNAs) are a large family of endogenous, non-coding RNAs, about 22 nucleotides long, which regulate gene expression through sequence-specific base pairing with target mRNAs. Extensive studies have shown that miRNA expression in the skin changes remarkably during distinct stages of the hair cycle in humans, mice, goats and sheep. Results In this study, the skin tissues were harvested from the three stages of hair follicle cycling (anagen, catagen and telogen) in a fibre-producing goat breed. In total, 63,109,004 raw reads were obtained by Solexa sequencing and 61,125,752 clean reads remained for the small RNA digitalisation analysis. This resulted in the identification of 399 conserved miRNAs; among these, 326 miRNAs were expressed in all three follicular cycling stages, whereas 3, 12 and 11 miRNAs were specifically expressed in anagen, catagen, and telogen, respectively. We also identified 172 potential novel miRNAs by Mireap, 36 miRNAs were expressed in all three cycling stages, whereas 23, 29 and 44 miRNAs were specifically expressed in anagen, catagen, and telogen, respectively. The expression level of five arbitrarily selected miRNAs was analyzed by quantitative PCR, and the results indicated that the expression patterns were consistent with the Solexa sequencing results. Gene Ontology and KEGG pathway analyses indicated that five major biological pathways (Metabolic pathways, Pathways in cancer, MAPK signalling pathway, Endocytosis and Focal adhesion) accounted for 23.08% of target genes among 278 biological functions, indicating that these pathways are likely to play significant roles during hair cycling. Conclusions During all hair cycle stages of cashmere goats, a large number of conserved and novel miRNAs were identified through a high-throughput sequencing approach. This study enriches the Capra hircus miRNA databases and provides a comprehensive miRNA transcriptome profile in the skin of goats during the hair follicle cycle. PMID

  11. Comparative Transcriptome Analysis of Fetal Skin Reveals Key Genes Related to Hair Follicle Morphogenesis in Cashmere Goats

    PubMed Central

    Yan, Hailong; Zeng, Jie; Ma, Sen; Niu, Yiyuan; Zhou, Guangxian; Jiang, Yu; Chen, Yulin

    2016-01-01

    Cashmere goat skin contains two types of hair follicles (HF): primary hair follicles (PHF) and secondary hair follicles (SHF). Although multiple genetic determinants associated with HF formation have been identified, the molecules that determine the independent morphogenesis of HF in cashmere goats remain elusive. The growth and development of SHF directly influence the quantity and quality of cashmere production. Here, we report the transcriptome profiling analysis of nine skin samples from cashmere goats using 60- and 120-day-old embryos (E60 and E120, respectively), as well as newborns (NB), through RNA-sequencing (RNA-seq). HF morphological changes indicated that PHF were initiated at E60, with maturation from E120, while differentiation of SHF was identified at E120 until formation of cashmere occurred after birth (NB). The RNA-sequencing analysis generated over 20.6 million clean reads from each mRNA library. The number of differentially expressed genes (DEGs) in E60 vs. E120, E120 vs. NB, and E60 vs. NB were 1,024, 0 and 1,801, respectively, indicating that no significant differences were found at transcriptomic levels between E120 and NB. Key genes including B4GALT4, TNC, a-integrin, and FGFR1, were up-regulated and expressed in HF initiation from E60 to E120, while regulatory genes such as GPRC5D, PAD3, HOXC13, PRR9, VSIG8, LRRC15, LHX2, MSX-2, and FOXN1 were up-regulated and expressed in HF keratinisation and hair shaft differentiation from E120 and NB to E60. Several genes belonging to the KRT and KRTAP gene families were detected throughout the three HF developmental stages. The transcriptional trajectory analyses of all DEGs indicated that immune privilege, glycosaminoglycan biosynthesis, extracellular matrix receptor interaction, and growth factor receptors all played dominant roles in the epithelial-mesenchymal interface and HF formation. We found that the Wnt, transforming growth factor-beta/bone morphogenetic protein, and Notch family members

  12. On-line diffusion profile of a lipophilic model dye in different depths of a hair follicle in human scalp skin.

    PubMed

    Grams, Ylva Y; Whitehead, Lynne; Lamers, Gerda; Sturmann, Nico; Bouwstra, Joke A

    2005-10-01

    In skin and hair research, drug targeting to the hair follicle is of great interest in the treatment of skin diseases. The aim of this study is to visualize on-line the diffusion processes of a model fluorophore into the hair follicle at different depths using fresh human scalp skin and confocal laser scanning microscopy. Up to a depth of 500 microm in the skin, a fast increase of fluorescence is observed in the gap followed by accumulation of the dye in the hair cuticle. Penetration was also observed via the stratum corneum and the epidermis. Little label reached depths greater than 2000 microm. Fat cells accumulated the label fastest, followed by the cuticular area and the outer root sheath of the hair follicle. Sweat glands revealed very low staining, whereas the bulb at a depth of 4000 microm was visualized only by autofluorescence. From this study, we conclude that on-line visualization is a promising technique to access diffusion processes in deep skin layers even on a cellular level. Furthermore, we conclude that the gap and the cuticle play an important role in the initial diffusion period with the label in the cuticle originating from the gap.

  13. Mitochondrial function in murine skin epithelium is crucial for hair follicle morphogenesis and epithelial-mesenchymal interactions.

    PubMed

    Kloepper, Jennifer E; Baris, Olivier R; Reuter, Karen; Kobayashi, Ken; Weiland, Daniela; Vidali, Silvia; Tobin, Desmond J; Niemann, Catherin; Wiesner, Rudolf J; Paus, Ralf

    2015-03-01

    Here, we studied how epithelial energy metabolism impacts overall skin development by selectively deleting intraepithelial mtDNA in mice by ablating a key maintenance factor (Tfam(EKO)), which induces loss of function of the electron transport chain (ETC). Quantitative (immuno)histomorphometry demonstrated that Tfam(EKO) mice showed significantly reduced hair follicle (HF) density and morphogenesis, fewer intrafollicular keratin15+ epithelial progenitor cells, increased apoptosis, and reduced proliferation. Tfam(EKO) mice also displayed premature entry into (aborted) HF cycling by apoptosis-driven HF regression (catagen). Ultrastructurally, Tfam(EKO) mice exhibited severe HF dystrophy, pigmentary abnormalities, and telogen-like condensed dermal papillae. Epithelial HF progenitor cell differentiation (Plet1, Lrig1 Lef1, and β-catenin), sebaceous gland development (adipophilin, Scd1, and oil red), and key mediators/markers of epithelial-mesenchymal interactions during skin morphogenesis (NCAM, versican, and alkaline phosphatase) were all severely altered in Tfam(EKO) mice. Moreover, the number of mast cells, major histocompatibility complex class II+, or CD11b+ immunocytes in the skin mesenchyme was increased, and essentially no subcutis developed. Therefore, in contrast to their epidermal counterparts, pilosebaceous unit stem cells depend on a functional ETC. Most importantly, our findings point toward a frontier in skin biology: the coupling of HF keratinocyte mitochondrial function with the epithelial-mesenchymal interactions that drive overall development of the skin and its appendages.

  14. Optical Monitoring of Living Nerve Terminal Labeling in Hair Follicle Lanceolate Endings of the Ex Vivo Mouse Ear Skin

    PubMed Central

    Bewick, Guy S.; Banks, Robert W.

    2016-01-01

    A novel dissection and recording technique is described for optical monitoring staining and de-staining of lanceolate terminals surrounding hair follicles in the skin of the mouse pinna. The preparation is simple and relatively fast, reliably yielding extensive regions of multiple labeled units of living nerve terminals to study uptake and release of styryl pyridinium dyes extensively used in studies of vesicle recycling. Subdividing the preparations before labeling allows test vs. control comparisons in the same ear from a single individual. Helpful tips are given for improving the quality of the preparation, the labeling and the imaging parameters. This new system is suitable for assaying pharmacologically and mechanically-induced uptake and release of these vital dyes in lanceolate terminals in both wild-type and genetically modified animals. Examples of modulatory influences on labeling intensity are given. PMID:27077818

  15. Optical Monitoring of Living Nerve Terminal Labeling in Hair Follicle Lanceolate Endings of the Ex Vivo Mouse Ear Skin.

    PubMed

    Bewick, Guy S; Banks, Robert W

    2016-04-05

    A novel dissection and recording technique is described for optical monitoring staining and de-staining of lanceolate terminals surrounding hair follicles in the skin of the mouse pinna. The preparation is simple and relatively fast, reliably yielding extensive regions of multiple labeled units of living nerve terminals to study uptake and release of styryl pyridinium dyes extensively used in studies of vesicle recycling. Subdividing the preparations before labeling allows test vs. control comparisons in the same ear from a single individual. Helpful tips are given for improving the quality of the preparation, the labeling and the imaging parameters. This new system is suitable for assaying pharmacologically and mechanically-induced uptake and release of these vital dyes in lanceolate terminals in both wild-type and genetically modified animals. Examples of modulatory influences on labeling intensity are given.

  16. Molecular characterization, expression and methylation status analysis of BMP4 gene in skin tissue of Liaoning cashmere goat during hair follicle cycle.

    PubMed

    Bai, Wen L; Dang, Yun L; Wang, Jiao J; Yin, Rong H; Wang, Ze Y; Zhu, Yu B; Cong, Yu Y; Xue, Hui L; Deng, Liang; Guo, Dan; Wang, Shi Q; Yang, Shu H

    2016-08-01

    Bone morphogenetic protein 4 (BMP4) is a member of the bone morphogenetic protein family (BMPs). It is involved in the development and cycle of hair follicle, as well as, is thought to be a potential candidate gene for cashmere traits in goats. In the present study, we isolated and characterized a full-length open reading frame (ORF) of BMP4 cDNA from the skin tissue of Liaoning cashmere goat, and investigated the transcriptional pattern and methylation status of BMP4 gene in skin tissue of this breed during different stages of hair follicle cycle. The sequence analysis indicated that the isolated cDNA was 1264-bp in length containing a complete ORF of 1230-bp. It encoded a precursor peptide of 409 amino acids with a signal peptide of 19 amino acids. The structural analysis indicated that goat BMP4 contains typical TGF-β propeptide and TGF-β domains. In skin tissue, BMP4 is generally transcribed in an ascendant pattern from anagen to telogen. The methylation level of 5' flanking regulatory region of BMP4 gene might be involved in its mRNA expression in skin tissue: a higher BMP4 methylation level in skin coincides with a lower expression of BMP4 mRNA. These results from the present work provided a foundation for further insight into the functional and regulatory characteristics of BMP4 in the development and cycle of hair follicle in Liaoning Cashmere goat.

  17. [The hair follicle as a target for gene therapy].

    PubMed

    Cotsarelis, G

    2002-05-01

    The hair follicle possesses progenitor cells required for continuous hair follicle cycling and for epidermal keratinocytes, melanocytes and Langerhans cells. These different cell types can be the target of topical gene delivery in the skin of the mouse. Using a combination of liposomes and DNA, we demonstrate the feasibility of targeting hair follicle cells in human scalp xenografts. We consider liposome composition and stage of the hair cycle as important parameters influencing transfection of human hair follicles. Transfection is possible only during the early anagen phase. Factors and obstacles for the use of gene therapy in treating alopecia and skin diseases are discussed. A theoretical framework for future treatment of cutaneous and systemic disorders using gene therapy is presented.

  18. Immunohistochemical study of hair follicle stem cells in regenerated hair follicles induced by Wnt10b

    PubMed Central

    Zhang, Yiming; Xing, Yizhan; Guo, Haiying; Ma, Xiaogen; Li, Yuhong

    2016-01-01

    The regulation of the periodic regeneration of hair follicles is complicated. Although Wnt10b has been reported to induce hair follicle regeneration, the characteristics of induced hair follicles, especially the target cells of Wnt10b, have not yet been clearly elucidated. Thus, we systematically evaluated the expression and proliferation patterns of Wnt10b-induced hair follicles. We found that Wnt10b promoted the proliferation of hair follicle stem cells from 24 hours after AdWnt10b injection. Seventy-two hours after AdWnt10b injection, cells outside of bulge area began to proliferate. When the induced hair follicle entered full anagen, although the hair follicle stem cells were normal, canonical Wnt signaling was maintained in the hair precortex cells. Our results reveal that the target cells that overexpressed Wnt10b included hair follicle stem cells, hair precortex cells, and matrix cells. PMID:27766026

  19. Central anatomy of individual rapidly adapting low-threshold mechanoreceptors innervating the "hairy" skin of newborn mice: early maturation of hair follicle afferents.

    PubMed

    Woodbury, C J; Ritter, A M; Koerber, H R

    2001-07-30

    Adult skin sensory neurons exhibit characteristic projection patterns in the dorsal horn of the spinal gray matter that are tightly correlated with modality. However, little is known about how these patterns come about during the ontogeny of the distinct subclasses of skin sensory neurons. To this end, we have developed an intact ex vivo somatosensory system preparation in neonatal mice, allowing single, physiologically identified cutaneous afferents to be iontophoretically injected with Neurobiotin for subsequent histological analyses. The present report, centered on rapidly adapting mechanoreceptors, represents the first study of the central projections of identified skin sensory neurons in neonatal animals. Cutaneous afferents exhibiting rapidly adapting responses to sustained natural stimuli were encountered as early as recordings were made. Well-stained representatives of coarse (tylotrich and guard) and fine-diameter (down) hair follicle afferents, along with a putative Pacinian corpuscle afferent, were recovered from 2-7-day-old neonates. All were characterized by narrow, uninflected somal action potentials and generally low mechanical thresholds, and many could be activated via deflection of recently erupted hairs. The central collaterals of hair follicle afferents formed recurrent, flame-shaped arbors that were essentially miniaturized replicas of their adult counterparts, with identical laminar terminations. The terminal arbors of down hair afferents, previously undescribed in rodents, were distinct and consistently occupied a more superficial position than tylotrich and guard hair afferents. Nevertheless, the former extended no higher than the middle of the incipient substantia gelatinosa, leaving a clear gap more dorsally. In all major respects, therefore, hair follicle afferents display the same laminar specificity in neonates as they do in adults. The widely held misperception that their collaterals extend exuberant projections into pain

  20. Proteomic Analysis of Hair Follicles

    NASA Astrophysics Data System (ADS)

    Ishioka, Noriaki; Terada, Masahiro; Yamada, Shin; Seki, Masaya; Takahashi, Rika; Majima, Hideyuki J.; Higashibata, Akira; Mukai, Chiaki

    2013-02-01

    Hair root cells actively divide in a hair follicle, and they sensitively reflect physical conditions. By analyzing the human hair, we can know stress levels on the human body and metabolic conditions caused by microgravity environment and cosmic radiation. The Japan Aerospace Exploration Agency (JAXA) has initiated a human research study to investigate the effects of long-term space flight on gene expression and mineral metabolism by analyzing hair samples of astronauts who stayed in the International Space Station (ISS) for 6 months. During long-term flights, the physiological effects on astronauts include muscle atrophy and bone calcium loss. Furthermore, radiation and psychological effects are important issue to consider. Therefore, an understanding of the effects of the space environment is important for developing countermeasures against the effects experienced by astronauts. In this experiment, we identify functionally important target proteins that integrate transcriptome, mineral metabolism and proteome profiles from human hair. To compare the protein expression data with the gene expression data from hair roots, we developed the protein processing method. We extracted the protein from five strands of hair using ISOGEN reagents. Then, these extracted proteins were analyzed by LC-MS/MS. These collected profiles will give us useful physiological information to examine the effect of space flight.

  1. Nanoparticle-based targeting of vaccine compounds to skin antigen-presenting cells by hair follicles and their transport in mice.

    PubMed

    Mahe, Brice; Vogt, Annika; Liard, Christelle; Duffy, Darragh; Abadie, Valérie; Bonduelle, Olivia; Boissonnas, Alexandre; Sterry, Wolfram; Verrier, Bernard; Blume-Peytavi, Ulrike; Combadiere, Behazine

    2009-05-01

    Particle-based drug delivery systems target active compounds to the hair follicle and may result in a better penetration and higher efficiency of compound uptake by skin resident cells. As previously proposed, such delivery systems could be important tools for vaccine delivery. In this study, we investigated the penetration of solid fluorescent 40 or 200 nm polystyrene nanoparticles (NPs) as well as virus particles in murine skin to further investigate the efficacy of transcutaneously (TC) applied particulate vaccine delivery route. We demonstrated that 40 and 200 nm NPs and modified vaccinia Ankara (MVA) expressing the green-fluorescent protein penetrated deeply into hair follicles and were internalized by perifollicular antigen-presenting cells (APCs). Fibered-based confocal microscopy analyses allowed visualizing in vivo particle penetration along the follicular duct, diffusion into the surrounding tissue, uptake by APCs and transport to the draining lymph nodes. The application of small particles, such as ovalbumin coding DNA or MVA, induced both humoral and cellular immune responses. Furthermore, TC applied MVA induced protection against vaccinia virus challenge. Our results strengthen the concept of TC targeting of cutaneous APCs by hair follicles and will contribute to the development of advanced vaccination protocols using NPs or viral vectors.

  2. Direct immunofluorescence on hair follicles--present and future perspectives.

    PubMed

    Alexandru, Adina; Zurac, Sabina; Salavastru, Carmen M; Andrei, Razvan; Tebeica, Tiberiu; Staniceanu, Florica; Tiplica, George S

    2013-06-01

    Direct immunofluorescence (DIF) is an important tool for evaluating bullous autoimmune and connective tissue disorders. We report 21 cases of pemphigus vulgaris, bullous pemphigoid and lupus erythematosus that were investigated by performing DIF on scalp hair follicles. The study was done using a simplified technique of preparing the hairs for DIF testing. The anagen hairs tested positive in pemphigus vulgaris patients while the telogen hairs were negative. In bullous pemphigoid and lupus erythematosus cases hair DIF presented negative results.Hair DIF has the potential of taking the place of skin or mucosal DIF in pemphigus patients if performed on anagen hair follicles. The technique used to perform hair DIF is important in obtaining reliable results and eliminating the possibility of generating false-negative testing. Larger studies are needed in order to validate this method.

  3. CD34 EXPRESSION BY HAIR FOLLICLE STEM CELLS IS REQUIRED FOR SKIN TUMOR DEVELOPMENT IN MICE

    EPA Science Inventory

    We used knockout mice to show that a cell surface protein called CD34 is required for skin tumor formation in mice. Wild type mice treated with 7-12-Dimethylbenz(a)anthracene (DMBA) and a tumor promoter developed papillomas. When we treated CD34 knockout (KO) mice the same way, n...

  4. A highly enriched niche of precursor cells with neuronal and glial potential within the hair follicle dermal papilla of adult skin.

    PubMed

    Hunt, David P J; Morris, Paul N; Sterling, Jane; Anderson, Jane A; Joannides, Alexis; Jahoda, Colin; Compston, Alastair; Chandran, Siddharthan

    2008-01-01

    Skin-derived precursor cells (SKPs) are multipotent neural crest-related stem cells that grow as self-renewing spheres and are capable of generating neurons and myelinating glial cells. SKPs are of clinical interest because they are accessible and potentially autologous. However, although spheres can be readily isolated from embryonic and neonatal skin, SKP frequency falls away sharply in adulthood, and primary sphere generation from adult human skin is more problematic. In addition, the culture-initiating cell population is undefined and heterogeneous, limiting experimental studies addressing important aspects of these cells such as the behavior of endogenous precursors in vivo and the molecular mechanisms of neural generation. Using a combined fate-mapping and microdissection approach, we identified and characterized a highly enriched niche of neural crest-derived sphere-forming cells within the dermal papilla of the hair follicle of adult skin. We demonstrated that the dermal papilla of the rodent vibrissal follicle is 1,000-fold enriched for sphere-forming neural crest-derived cells compared with whole facial skin. These "papillaspheres" share a phenotypic and developmental profile similar to that of SKPs, can be readily expanded in vitro, and are able to generate both neuronal and glial cells in response to appropriate cues. We demonstrate that papillaspheres can be efficiently generated and expanded from adult human facial skin by microdissection of a single hair follicle. This strategy of targeting a highly enriched niche of sphere-forming cells provides a novel and efficient method for generating neuronal and glial cells from an accessible adult somatic source that is both defined and minimally invasive.

  5. Gradient-dependent release of the model drug TRITC-dextran from FITC-labeled BSA hydrogel nanocarriers in the hair follicles of porcine ear skin.

    PubMed

    Tran, Ngo Bich Nga Nathalie; Knorr, Fanny; Mak, Wing Cheung; Cheung, Kwan Yee; Richter, Heike; Meinke, Martina; Lademann, Jürgen; Patzelt, Alexa

    2016-09-29

    Hair follicle research is currently focused on the development of drug-loaded nanocarriers for the targeting of follicular structures in the treatment of skin and hair follicle-related disorders. In the present study, a dual-label nanocarrier system was implemented in which FITC-labeled BSA hydrogel nanocarriers loaded with the model drug and dye TRITC-dextran were applied topically to porcine ear skin. Follicular penetration and the distribution of both dyes corresponding to the nanocarriers and the model drug in the follicular ducts subsequent to administration to the skin were investigated using confocal laser scanning microscopy. The release of TRITC-dextran from the particles was induced by washing of the nanocarriers, which were kept in a buffer containing TRITC-labeled dextran to balance out the diffusion of the dextran during storage, thereby changing the concentration gradient. The results showed a slightly but statistically significantly deeper follicular penetration of fluorescent signals corresponding to TRITC-dextran as opposed to fluorescence corresponding to the FITC-labeled particles. The different localizations of the dyes in the cross-sections of the skin samples evidenced the release of the model drug from the labeled nanoparticles.

  6. The appearance, density, and distribution of Merkel cells in human embryonic and fetal skin: their relation to sweat gland and hair follicle development.

    PubMed

    Kim, D K; Holbrook, K A

    1995-03-01

    The density and distribution of Merkel cells in human embryonic and fetal skin were studied using an immunolabeling technique on epidermal and dermal sheets obtained by ethylenediamine tetraacetic acid separation. Merkel cells were identified by the known cytokeratin markers CK20 and CK18. Merkel cells showed CK20 immunoreactivity as early as 56 d estimated gestational age (EGA) in the palmar epidermis (133.11 +/- 44.27 cells/mm2). The density increased rapidly, reaching a maximum of more than 1400 cells/mm2 at 80-90 d EGA. At this stage, the cells became distributed along the primary epidermal ridges. In the palmar epidermis of fetuses older than 100 d EGA, the distribution of Merkel cells showed the same pattern, but the density then decreased gradually. Merkel cells were not observed in ductal and glandular portions of eccrine sweat glands. In the epidermal sheets of hairy skin, a few cells were first seen in the fetus at 75 d EGA. At 100 d EGA, only a few Merkel cells were observed, mostly in the hair pegs and bulbous hair pegs. In the older fetus, ring-like arrangements and aggregates of Merkel cells were prominent in the infundibulum and bulge of hair follicles, respectively. Merkel cells were both globular and dendritic in shape. The ratio of dendritic to globular cells increased gradually until the period of highest Merkel cell density in both the glabrous and hairy skin. All Merkel cells located in the dermis were globular in shape. In accord with the results obtained, we postulate that Merkel cells may have some functional role in the formation and proliferation of eccrine sweat glands and hair follicle anlagen in developing skin.

  7. Dynamic ultrastructural changes of the connective tissue sheath of human hair follicles during hair cycle.

    PubMed

    Ito, M; Sato, Y

    1990-01-01

    Ultrastructural changes of the connective tissue sheath (CTS), including the hyaline membrane, of human hair follicles during the hair cycle, were studied in normal scalp skin specimens. In early anagen, the CTS was composed of a thin basal lamina and surrounding collagen tissue. The collagen tissue gradually thickened during the development of the hair and hair follicle. In mature anagen hair follicles, the collagen tissue was separated into three layers. The inner collagen layer, just outside the basal lamina, was thin and composed of collagen fibres running longitudinally parallel to the hair axis. The middle collagen layer was very thick with its collagen fibres running transversely against the hair axis and surrounding the inner hair tissue. Many fibroblasts were present among the collagen fibres in the middle layer, whereas the inner layer contained almost none. In the outer collagen layer, collagen fibres ran in various directions parallel to the outer surface of the outer root sheath cells. In late anagen, the basal lamina became very thick. In catagen, the basal lamine and the inner collagen layer became corrugated and showed oedematous change and degeneration. Surrounding fibroblasts showed active production of new collagen fibres, which seemed to fill the spaces left by the retraction of the hair follicle and hyaline membrane. These ultrastructural changes of the CTS show that there may be dynamic metabolic changes of the connective tissue around human hair follicles during the hair cycle.

  8. Human hair follicle: reservoir function and selective targeting.

    PubMed

    Blume-Peytavi, U; Vogt, A

    2011-10-01

    Penetration of topically applied compounds may occur via the stratum corneum, skin appendages and hair follicles. The follicular infundibulum increases the surface area, disrupts the epidermal barrier towards the lower parts of the follicle, and serves as a reservoir. Topical delivery of active compounds to specific targets within the skin, especially to distinct hair follicle compartments or cell populations, may help to treat local inflammatory reactions selectively, with reduced systemic side-effects. Various in vitro and in vivo methods exist for studying the hair follicle structure and follicular penetration pathways. These include cyanoacrylate skin surface stripping, confocal microscopy and cyanoacrylate scalp follicle biopsy. The complex anatomical structure as well as the cyclical activity of the hair follicle must be taken into consideration when designing delivery systems. In addition, delivery into and retention inside the infundibular reservoir are controlled by, for example, molecule or particle size, their polarity and the type of preparation. Preferred penetration depth and storage time must also be considered. Particles with release mechanisms should be preferred; however, the release of drugs from nanoparticles still requires further investigations.

  9. The hair follicle and its stem cells as drug delivery targets.

    PubMed

    Hoffman, Robert M

    2006-05-01

    The hair follicle is a skin appendage with a complex structure containing many cell types that produce highly specialised proteins. The hair follicle is in a continuous cycle: anagen is the hair growth phase, catagen the involution phase and telogen is the resting phase. The follicle offers many potential therapeutic targets. Hoffman and colleagues have pioneered hair-follicle-specific targeting using liposomes to deliver small and large molecules, including genes. They have also pioneered ex vivo hair-follicle targeting with continued expression of the introduced gene following transplantation. Recently, it has been discovered that hair follicle stem cells are highly pluripotent and can form neurons, glial cells and other cell types, and this has suggested that hair follicle stem cells may serve as gene therapy targets for regenerative medicine.

  10. Topical liposome targeting of dyes, melanins, genes, and proteins selectively to hair follicles.

    PubMed

    Hoffman, R M

    1998-01-01

    For therapeutic and cosmetic modification of hair, we have developed a hair-follicle-selective macromolecule and small molecule targeting system with topical application of phosphatidylcholine-based liposomes. Liposome-entrapped melanins, proteins, genes, and small-molecules have been selectively targeted to the hair follicle and hair shafts of mice. Liposomal delivery of these molecules is time dependent. Negligible amounts of delivered molecules enter the dermis, epidermis, or bloodstream thereby demonstrating selective follicle delivery. Naked molecules are trapped in the stratum corneum and are unable to enter the follicle. The potential of the hair-follicle liposome delivery system for therapeutic use for hair disease as well as for cosmesis has been demonstrated in 3-dimensional histoculture of hair-growing skin and mouse in vivo models. Topical liposome selective delivery to hair follicles has demonstrated the ability to color hair with melanin, the delivery of the active lac-Z gene to hair matrix cells and delivery of proteins as well. Liposome-targeting of molecules to hair follicles has also been achieved in human scalp in histoculture. Liposomes thus have high potential in selective hair follicle targeting of large and small molecules, including genes, opening the field of gene therapy and other molecular therapy of the hair process to restore hair growth, physiologically restore or alter hair pigment, and to prevent or accelerate hair loss.

  11. Hair Follicle Morphogenesis in the Treatment of Mouse Full-Thickness Skin Defects Using Composite Human Acellular Amniotic Membrane and Adipose Derived Mesenchymal Stem Cells

    PubMed Central

    Minjuan, Wu; Jun, Xiong; Shiyun, Shao; Sha, Xu; Haitao, Ni

    2016-01-01

    Early repair of skin injury and maximal restoration of the function and appearance have become important targets of clinical treatment. In the present study, we observed the healing process of skin defects in nude mice and structural characteristics of the new skin after transplantation of isolated and cultured adipose derived mesenchymal stem cells (ADMSCs) onto the human acellular amniotic membrane (AAM). The result showed that ADMSCs were closely attached to the surface of AAM and grew well 24 h after seeding. Comparison of the wound healing rate at days 7, 14, and 28 after transplantation showed that ADMSCs seeded on AAM facilitated the healing of full-thickness skin wounds more effectively as compared with either hAM or AAM alone, indicating that ADMSCs participated in skin regeneration. More importantly, we noticed a phenomenon of hair follicle development during the process of skin repair. Composite ADMSCs and AAM not only promoted the healing of the mouse full-thickness defects but also facilitated generation of the appendages of the affected skin, thus promoting restoration of the skin function. Our results provide a new possible therapy idea for the treatment of skin wounds with respect to both anatomical regeneration and functional restoration. PMID:27597871

  12. The feasibility of targeted selective gene therapy of the hair follicle.

    PubMed

    Li, L; Hoffman, R M

    1995-07-01

    Loss of hair and hair colour is associated with ageing, and when it involves the scalp hair, it can be distressing to both sexes. Hair loss resulting from cancer chemotherapy is particularly distressing. However, safe, effective therapies directed to hair have only just started to be developed. The hair follicle is a complex skin appendage composed of epidermal and dermal tissue, with specialized keratinocytes, the hair matrix cells, forming the hair shaft. Specific therapy of the hair follicle depends on selective targeting of specific cells of the hair follicle. We have developed the histoculture of intact hair-growing skin on sponge-gel matrices. We have recently found in histocultured skin that liposomes can selectively target hair follicles to deliver both small and large molecules. That liposomes can target the hair follicle for delivery has been confirmed independently. Two decades ago we introduced the technique of entrapping DNA in liposomes for use in gene therapy. In this report we describe the selective targeting of the lacZ reporter gene to the hair follicles in mice after topical application of the gene entrapped in liposomes. These results demonstrate that highly selective, safe gene therapy for the hair process is feasible.

  13. Activin B promotes initiation and development of hair follicles in mice.

    PubMed

    Jia, Qin; Zhang, Min; Kong, Yanan; Chen, Shixuan; Chen, Yinghua; Wang, Xueer; Zhang, Lei; Lang, Weiya; Zhang, Lu; Zhang, Lin

    2013-01-01

    Activin B has been reported to promote the regeneration of hair follicles during wound healing. However, its role in the development and life cycle of hair follicles has not been elucidated. In our study, the effect of activin B on mouse hair follicles of cultured and neonatal mouse skin was investigated. In these models, PBS or activin B (5, 10 or 50 ng/ml) was applied, and hair follicle development was monitored. Hair follicle initiation and development was examined using hematoxylin and eosin staining, alkaline phosphatase activity staining, Oil Red O+ staining, and the detection of TdT-mediated dUTP-biotin nick end-labeling cell apoptosis. Activin B was found to efficiently induce the initiation of hair follicles in the skin of both cultured and neonatal mice and to promote the development of hair follicles in neonatal mouse skin. Moreover, activin-B-treated hair follicles were observed to enter the anagen stage from the telogen stage and to remain in the anagen stage. These results demonstrate that activin B promotes the initiation and development of hair follicles in mice.

  14. Hair follicle stem cell marker nestin expression in regenerating hair follicles of patients with alopecia areata.

    PubMed

    Amoh, Yasuyuki; Maejima, Hideki; Niiyama, Shiro; Mii, Sumiyuki; Hamada, Yuko; Saito, Norimitsu; Katsuoka, Kensei

    2011-01-01

    Cells that are nestin positive and keratin 15 (K15) negative are located in the hair follicle pluripotent stem cell (hfPS) area (hfPSA). The hfPSA is located within the root of the sebaceous glands, in a region just above the hair follicle bulge area. In the current study, we investigated the expression pattern of the stem cell marker nestin in the hair follicle cycling of patients with alopecia areata. In the normal human scalp, the majority of hair follicles are in the anagen phase of development. While it is often difficult to identify nestin expression in late anagen phases, nestin-expressing cells are easily identified in proliferating cells located in the hfPSA of the growing early and middle anagen phase hair follicles. In patients exhibiting alopecia areata, the middle anagen hair follicles with growing cells were found to be nestin positive and K15 negative. In contrast, the hair follicles undergoing degradation in alopecia areata patients demonstrated lymphocytic infiltration within the nestin- and K15-negative dermal papilla cells. Both the nestin-positive hfPSA and K15-positive hair follicle bulge areas were not damaged in all phases. In addition, the regenerating early anagen hair follicles demonstrated nestin-positive and K15-negative cells within the dermal papilla and in the area surrounding the hair bulb. These results suggest that the nestin-positive cells play an important role not only in the hfPSA, but also in the dermal papilla in the regenerating hair follicle.

  15. Transglutaminase from Hair Follicle of Guinea Pig

    PubMed Central

    Chung, S. I.; Folk, J. E.

    1972-01-01

    Two transglutaminases are found in homogenates of the inner root sheaths of guinea pig hair-follicles. One is indistinguishable from the well-characterized liver transglutaminase [J. Biol. Chem., 246, 1093 (1971)]. The other, which is present in far greater quantity, has not been detected in other organs or tissues. Gel filtration and polyacrylamide gel electrophoresis studies indicate that the native hair-follicle enzyme, of molecular weight 54,000, is composed of two subunits of identical molecular weight. Specificity studies suggest that the intermolecular cross-linking of fibrin and fibrinogen that is catalyzed by this enzyme is a result of the formation of ε(γ-glutamyl)lysine bonds. The probable participation of hair-follicle transglutaminase in the formation of these cross-links in the proteins of hair is discussed. Images PMID:4501114

  16. Hair follicle targeting, penetration enhancement and Langerhans cell activation make cyanoacrylate skin surface stripping a promising delivery technique for transcutaneous immunization with large molecules and particle-based vaccines.

    PubMed

    Vogt, Annika; Hadam, Sabrina; Deckert, Iliane; Schmidt, Julia; Stroux, Andrea; Afraz, Zahra; Rancan, Fiorenza; Lademann, Jürgen; Combadiere, Behazine; Blume-Peytavi, Ulrike

    2015-01-01

    Transcutaneous immunization (TCI) requires targeting of a maximum number of skin antigen-presenting cells as non-invasive as possible on small skin areas. In two clinical trials, we introduced cyanoacrylate skin surface stripping (CSSS) as a safe method for TCI. Here, using ex vivo human skin, we demonstrate that one CSSS procedure removed only 30% of stratum corneum, but significantly increased the penetration of 200 nm polystyrene particles deep into vellus and intermediate hair follicles from where they could not been retrieved by conventional tape stripping. Two subsequent CSSS had no striking additional effect. CSSS increased particle penetration in superficial stratum corneum and induced Langerhans cell activation. Formulation in amphiphilic ointment or massage did not substantially influences the interfollicular penetration profiles. Hair follicle (HF) targeting by CSSS could become a highly effective tool for TCI when combined with carrier-based delivery and is gaining new attention as our understanding on the HF immune system increases.

  17. Combination of infrared thermography and reflectance spectroscopy for precise classification of hair follicle stage

    NASA Astrophysics Data System (ADS)

    Wang, Jianru; Guan, Yue; Liu, Caihua; Zhu, Dan

    2015-03-01

    Hair follicles enjoy continual cycle of anagen, catagen and telogen all life. They not only provide a unique opportunity to study the physiological mechanism of organ regeneration, but also benefit to guide the treatment of organ repair in regenerative medicine. Usually, the histological examination as a gold standard has been applied to determine the stage of hair follicle cycle, but noninvasive classification of hair cycle in vivo remains unsolved. In this study, the thermal infrared imager was applied to measure the temperature change of mouse dorsal skin with hair follicle cycle, and the change of diffuse reflectance was monitored by the optical fiber spectrometer. Histological examination was used to verify the hair follicle stages. The results indicated that the skin temperature increased at the beginning of anagen. After having stayed a high value for several days, the temperature began to decrease. At the same time, the skin diffuse reflectance decreased until the end of this period. Then the temperature increased gradually after slightly decreased when the hair follicle entered into catagen stage, and the diffuse reflectance increased at this time. In telogen, both the temperature and the diffuse reflectance went back to a steady state all the time. Sub-stages of hair follicle cycle could be distinguished based on the joint curves. This study provided a new method to noninvasively recognize the hair follicle stage, and should be valuable for the basic and therapeutic investigations on hair regeneration.

  18. Integrated Analysis of the Roles of Long Noncoding RNA and Coding RNA Expression in Sheep (Ovis aries) Skin during Initiation of Secondary Hair Follicle

    PubMed Central

    Liu, Jianbin; Guo, Jian; Feng, Ruilin; Niu, Chune; Sun, Xiaoping; Yang, Bohui

    2016-01-01

    Initiation of hair follicle (HF) is the first and most important stage of HF morphogenesis. However the precise molecular mechanism of initiation of hair follicle remains elusive. Meanwhile, in previous study, the more attentions had been paid to the function of genes, while the roles of non-coding RNAs (such as long noncoding RNA and microRNA) had not been described. Therefore, the roles of long noncoding RNA(LncRNA) and coding RNA in sheep skin during the initiation of sheep secondary HF were integrated and analyzed, by using strand-specific RNA sequencing (ssRNA-seq).A total of 192 significant differentially expressed genes were detected, including 67 up-regulated genes and 125 down-regulated genes between stage 0 and stage 1 of HF morphogenesis during HF initiation. Only Wnt2, FGF20 were just significant differentially expressed among Wnt, Shh, Notch and BMP signaling pathways. Further expression profile analysis of lncRNAs showed that 884 novel lncRNAs were discovered in sheep skin expression profiles. A total of 15 lncRNAs with significant differential expression were detected, 6 up-regulated and 9 down-regulated. Among of differentially expressed genes and LncRNA, XLOC002437 lncRNA and potential target gene COL6A6 were all significantly down-regulated in stage 1. Furthermore, by using RNAhybrid, XLOC005698 may be as a competing endogenous RNA ‘‘sponges” oar-miR-3955-5p activity. Gene Ontology and KEGG pathway analyses indicated that the significantly enriched pathway was peroxisome proliferator-activated receptors (PPARs) pathway (corrected P-value < 0.05), indicating that PPAR pathway is likely to play significant roles during the initiation of secondary HF.Results suggest that the key differentially expressed genes and LncRNAs may be considered as potential candidate genes for further study on the molecular mechanisms of HF initiation, as well as supplying some potential values for understanding human hair disorders. PMID:27276011

  19. Alterations in hair follicle dynamics in women.

    PubMed

    Piérard-Franchimont, Claudine; Piérard, Gérald E

    2013-01-01

    Endocrine changes supervening after parturition and menopause participate in the control of sebum production and hair growth modulation. The ensuing conditions include some peculiar aspects of hair loss (effluvium), alopecia, and facial hirsutism. The hair cycling is of major clinical relevance because most hair growth disorders result from disturbances in this chronobiological feature. Of note, any correlation between a biologic abnormality and hair cycling disturbance does not prove a relationship of causality. The proportion of postmenopausal women is rising in the overall population. Therefore, the prevalence of these hair follicle disturbances is globally on the rise. Current therapies aim at correcting the underlying hormonal imbalances, and at improving the overall cosmetic appearance. However, in absence of pathogenic diagnosis and causality criteria, chances are low that a treatment given by the whims of fate will adequately control hair effluvium. The risk and frequency of therapeutic inertia are further increased. When the hair loss is not controlled and/or compensated by growth of new hairs, several clinical aspects of alopecia inexorably develop. Currently, there is little evidence supporting any specific treatment for these endocrine hair disorders in post-partum and postmenopausal women. Current hair treatment strategies are symptomatic and nonspecific so current researchers aim at developing new, targeted methods.

  20. Putting the Human Hair Follicle Cycle on the Map.

    PubMed

    Panteleyev, Andrey A

    2016-01-01

    A detailed characterization of the normal (in situ) human hair follicle cycle, supplemented with expressional data on specific hair follicle markers, has been awaited by basic hair researchers and dermatologists. Combining this hair cycle guide, together with a thorough analysis of the human-on-mouse hair xenograft model, provides solid ground for examining human hair cycle biology and pathology and for hair cycle-related pharmacological testing.

  1. A Guide to Studying Human Hair Follicle Cycling In Vivo.

    PubMed

    Oh, Ji Won; Kloepper, Jennifer; Langan, Ewan A; Kim, Yongsoo; Yeo, Joongyeub; Kim, Min Ji; Hsi, Tsai-Ching; Rose, Christian; Yoon, Ghil Suk; Lee, Seok-Jong; Seykora, John; Kim, Jung Chul; Sung, Young Kwan; Kim, Moonkyu; Paus, Ralf; Plikus, Maksim V

    2016-01-01

    Hair follicles (HFs) undergo lifelong cyclical transformations, progressing through stages of rapid growth (anagen), regression (catagen), and relative "quiescence" (telogen). Given that HF cycling abnormalities underlie many human hair growth disorders, the accurate classification of individual cycle stages within skin biopsies is clinically important and essential for hair research. For preclinical human hair research purposes, human scalp skin can be xenografted onto immunocompromised mice to study human HF cycling and manipulate long-lasting anagen in vivo. Although available for mice, a comprehensive guide on how to recognize different human hair cycle stages in vivo is lacking. In this article, we present such a guide, which uses objective, well-defined, and reproducible criteria, and integrates simple morphological indicators with advanced, (immuno)-histochemical markers. This guide also characterizes human HF cycling in xenografts and highlights the utility of this model for in vivo hair research. Detailed schematic drawings and representative micrographs provide examples of how best to identify human HF stages, even in suboptimally sectioned tissue, and practical recommendations are given for designing human-on-mouse hair cycle experiments. Thus, this guide seeks to offer a benchmark for human hair cycle stage classification, for both hair research experts and newcomers to the field.

  2. A guide to studying human hair follicle cycling in vivo

    PubMed Central

    Oh, Ji Won; Kloepper, Jennifer; Langan, Ewan A.; Kim, Yongsoo; Yeo, Joongyeub; Kim, Min Ji; Hsi, Tsai-Ching; Rose, Christian; Yoon, Ghil Suk; Lee, Seok-Jong; Seykora, John; Kim, Jung Chul; Sung, Young Kwan

    2015-01-01

    Hair follicles (HFs) undergo life-long cyclical transformations, progressing through stages of rapid growth (anagen), regression (catagen), and relative “quiescence” (telogen). Since HF cycling abnormalities underlie many human hair growth disorders, the accurate classification of individual cycle stages within skin biopsies is clinically important and essential for hair research. For preclinical human hair research purposes, human scalp skin can be xenografted onto immunocompromised mice to study human HF cycling and manipulate long-lasting anagen in vivo. While available for mice, a comprehensive guide on how to recognize different human hair cycle stages in vivo is lacking. Here, we present such a guide, which uses objective, well-defined, and reproducible criteria and integrates simple morphological indicators with advanced, (immuno)-histochemical markers. This guide also characterizes human HF cycling in xenografts and highlights the utility of this model for in vivo hair research. Detailed schematic drawings and representative micrographs provide examples of how best to identify human HF stages, even in sub-optimally sectioned tissue, and practical recommendations are given for designing human-on-mouse hair cycle experiments. Thus, this guide seeks to offer a benchmark for human hair cycle stage classification, for both hair research experts and newcomers to the field. PMID:26763421

  3. Effects of Wnt-10b on hair shaft growth in hair follicle cultures

    SciTech Connect

    Ouji, Yukiteru . E-mail: oujix@naramed-u.ac.jp; Yoshikawa, Masahide; Moriya, Kei; Ishizaka, Shigeaki

    2007-08-03

    Wnts are deeply involved in the proliferation and differentiation of skin epithelial cells. We previously reported the differentiation of cultured primary skin epithelial cells toward hair shaft and inner root sheath (IRS) of the hair follicle via {beta}-catenin stabilization caused by Wnt-10b, however, the effects of Wnt-10b on cultured hair follicles have not been reported. In the present study, we examined the effects of Wnt-10b on shaft growth using organ cultures of whisker hair follicles in serum-free conditions. No hair shaft growth was observed in the absence of Wnt-10b, whereas its addition to the culture promoted elongation of the hair shaft, intensive incorporation of BrdU in matrix cells flanking the dermal papilla (DP), and {beta}-catenin stabilization in DP and IRS cells. These results suggest a promoting effect of Wnt-10b on hair shaft growth that is involved with stimulation of the DP via Wnt-10b/{beta}-catenin signalling, proliferation of matrix cells next to the DP, and differentiation of IRS cells by Wnt-10b.

  4. Effect of helium-neon laser irradiation on hair follicle growth cycle of Swiss albino mice.

    PubMed

    Shukla, S; Sahu, K; Verma, Y; Rao, K D; Dube, A; Gupta, P K

    2010-01-01

    We report the results of a study carried out to investigate the effect of helium-neon (He-Ne) laser (632.8 nm) irradiation on the hair follicle growth cycle of testosterone-treated and untreated mice. Both histology and optical coherence tomography (OCT) were used for the measurement of hair follicle length and the relative percentage of hair follicles in different growth phases. A positive correlation (R = 0.96) was observed for the lengths of hair follicles measured by both methods. Further, the ratios of the lengths of hair follicles in the anagen and catagen phases obtained by both methods were nearly the same. However, the length of the hair follicles measured by both methods differed by a factor of 1.6, with histology showing smaller lengths. He-Ne laser irradiation (at approximately 1 J/cm(2)) of the skin of both the control and the testosterone-treated mice was observed to lead to a significant increase (p < 0.05) in % anagen, indicating stimulation of hair growth. The study also demonstrates that OCT can be used to monitor the hair follicle growth cycle, and thus hair follicle disorders or treatment efficacy during alopecia.

  5. Fundamental hair follicle biology and fine fibre production in animals.

    PubMed

    Galbraith, H

    2010-09-01

    Hair 'fine' fibre is an important commercial product of farmed and certain wild animal species. The fibre is produced in follicles embedded in skin. These have properties in common with other tissues of the integument and have importance in determining yield and quality of fibre. Means of understanding and improving these characteristics are informed by knowledge of integumental and follicle biology. This paper reviews contemporary information that identifies the major fibre-producing species and their production characteristic. It surveys knowledge describing fundamental biology of the integument and considers information derived for the hair follicle from studies on a number of species including genetically modified mice. It identifies the composition of the follicle and describes components and interrelationships between epidermal hair-fibre producing epidermis and fibroblast- and connective tissue-containing dermis. The structure of different primary and secondary follicle types, and associated structures, are described. Focus is given to the alterations in anatomy and in behaviour from active to inactive state, which occurs during the hair follicle cycle. Information is provided on the anatomical substructures (hair medulla, cortex, cuticles and supporting sheaths and dermal papilla), cellular and extracellular composition, and adhesion and chemical signalling systems, which regulate development from the early embryo to post-natal state and subsequent cycling. Such signalling involves the dermis and its specialist fibroblasts, which secrete signalling molecules, which along with those from local epidermis and systemic sources, largely determine structure and function of epidermal cells. Such chemical signalling typically includes endocrine-, paracrine-, autocrine- and juxtacrine-acting molecules and interactions with their receptors located on cell membranes or intracellularly with transduction of message mediated by transcription factors at gene level

  6. A simple assay for the study of human hair follicle damage induced by ionizing irradiation.

    PubMed

    Poeggeler, Burkhard; Bodó, Enikö; Nadrowitz, Roger; Dunst, Juergen; Paus, Ralf

    2010-08-01

    Due to its rapidly proliferating matrix keratinocytes, the hair follicle is highly sensitive to ionizing irradiation (IR)-induced skin damage and thus an instructive and clinically relevant model organ for investigating the effects of IR on rapidly dividing epithelial-mesenchymal interaction systems. Here, we have assessed the impact of IR on organ-cultured human scalp hair follicles. We show that IR significantly inhibits the proliferation and induces apoptosis of hair follicle matrix keratinocytes, disrupts normal hair follicle pigmentation, and upregulates a number of quantitative toxicity and viability markers (oxidative stress indicators, DNA oxidative damage, LDH release). This introduces human hair follicle organ culture as an excellent novel research tool for radiobiology and invites exploitation as a preclinical assay system for testing candidate radioprotectants.

  7. Trps1 deficiency inhibits the morphogenesis of secondary hair follicles via decreased Noggin expression

    SciTech Connect

    Sun, Yujing; Nakanishi, Masako; Sato, Fuyuki; Oikawa, Kosuke; Muragaki, Yasuteru; Zhou, Gengyin

    2015-01-16

    Highlights: • The number of secondary hair follicles is reduced by half in Trps1 KO embryonic skin compared to wild-type skin. • Noggin expression is significantly decreased and BMP signaling is promoted in Trps1 KO embryonic skin. • Treatment with a Noggin or BMP inhibitor rescued the decreased number of hair follicles in Trps1 KO skin graft cultures. • Cell proliferation and apoptosis of the epidermis were normalized by Noggin treatment. - Abstract: A representative phenotype of patients with tricho-rhino-phalangeal syndrome (TRPS) is sparse hair. To understand the developmental defects of these patient’s hair follicles, we analyzed the development of hair follicles histologically and biochemically using Trps1 deficient (KO) mice. First, we compared the numbers of primary hair follicles in wild-type (WT) and KO embryos at different developmental stages. No differences were observed in the E14.5 skins of WT and KO mice. However, at later time points, KO fetal skin failed to properly develop secondary hair follicles, and the number of secondary hair follicles present in E18.5 KO skin was approximately half compared to that of WT skin. Sonic hedgehog expression was significantly decreased in E17.5 KO skin, whereas no changes were observed in Eda/Edar expression in E14.5 or E17.5 skins. In addition, Noggin expression was significantly decreased in E14.5 and E17.5 KO skin compared to WT skin. In parallel with the suppression of Noggin expression, BMP signaling was promoted in the epidermal cells of KO skins compared to WT skins as determined by immunohistochemistry for phosphorylated Smad1/5/8. The reduced number of secondary hair follicles was restored in skin graft cultures treated with a Noggin and BMP inhibitor. Furthermore, decreased cell proliferation, and increased apoptosis in KO skin was rescued by Noggin treatment. Taken together, we conclude that hair follicle development in Trps1 KO embryos is impaired directly or indirectly by decreased Noggin

  8. Induced pluripotent stem cells from human hair follicle keratinocytes as a potential source for in vitro hair follicle cloning

    PubMed Central

    Lim, Sheng Jye; Ho, Shu Cheow; Mok, Pooi Ling; Tan, Kian Lee; Ong, Alan H.K.

    2016-01-01

    Background Human hair follicles are important for the renewal of new hairs and their development. The generation of induced pluripotent stem cells (iPSCs) from hair follicles is easy due to its accessibility and availability. The pluripotent cells derived from hair follicles not only have a higher tendency to re-differentiate into hair follicles, but are also more suited for growth in hair scalp tissue microenvironment. Methods In this study, human hair follicular keratinocytes were used to generate iPSCs, which were then further differentiated in vitro into keratinocytes. The derived iPSCs were characterised by using immunofluorescence staining, flow cytometry, and reverse-transcription PCR to check for its pluripotency markers expression. Results The iPSC clones expressed pluripotency markers such as TRA-1-60, TRA-1-81, SSEA4, OCT4, SOX2, NANOG, LEFTY, and GABRB. The well-formed three germ layers were observed during differentiation using iPSCs derived from hair follicles. The successful formation of keratioctyes from iPSCs was confirmed by the expression of cytokeratin 14 marker. Discussion Hair follicles represent a valuable keratinocytes source for in vitro hair cloning for use in treating hair balding or grafting in burn patients. Our significant findings in this report proved that hair follicles could be used to produce pluripotent stem cells and suggested that the genetic and micro-environmental elements of hair follicles might trigger higher and more efficient hair follicles re-differentiation. PMID:27867768

  9. Analysis of the penetration of a caffeine containing shampoo into the hair follicles by in vivo laser scanning microscopy

    NASA Astrophysics Data System (ADS)

    Lademann, J.; Richter, H.; Schanzer, S.; Klenk, A.; Sterry, W.; Patzelt, A.

    2010-02-01

    In previous in vitro investigations, it was demonstrated that caffeine is able to stimulate the hair growth. Therefore, a penetration of caffeine into the hair follicle is necessary. In the present study, in vivo laser scanning microscopy (LSM) was used to investigate the penetration and storage of a caffeine containing shampoo into the hair follicles. It was shown that a 2-min contact time of the shampoo with the skin was enough to accumulate significant parts of the shampoo in the hair follicles. A penetration of the shampoo up to a depth of approx. 200 μm could be detected, which represents the detection limit of the LSM. At this depth, the close network of the blood capillaries surrounding the hair follicles commences. Even after 24 h, the substance was still detectable in the hair follicles. This demonstrates the long-term reservoir function of the hair follicles for topically applied substances such as caffeine.

  10. Histological evaluation of hair follicle due to papain's depilatory effect.

    PubMed

    Traversa, Eduardo; Machado-Santelli, Gláucia Maria; Velasco, Maria Valéria Robles

    2007-04-20

    Histological alterations in the skin and hair follicle of mice were evaluated as a result of the application of gel and cream formulas containing papain as a harmless treatment for hirsutism. Papain is a proteolytic enzyme and it has been used in pharmaceutical, cosmetic and nutrition areas. The purpose of this study was to evaluate the efficacy of a depilatory product, through histological analysis using light microscopy. Gel and cream formulas containing papain were developed and daily applied on the back of two groups of mice for 31 days. The depilatory effect of the gel formula applied on the first group was less evident. The second group treated with the cream formula presented an intensive depilatory effect; the morphometrical analysis showed dilation of about 55% of the hair follicle lumen and an increase of the thickness of epidermis. Papain cream had a significantly higher depilatory effect than the papain gel.

  11. Modulating hair follicle size with Wnt10b/DKK1 during hair regeneration.

    PubMed

    Lei, Mingxing; Guo, Haiying; Qiu, Weiming; Lai, Xiangdong; Yang, Tian; Widelitz, Randall B; Chuong, Cheng-Ming; Lian, Xiaohua; Yang, Li

    2014-06-01

    Hair follicles have characteristic sizes corresponding to their cycle-specific stage. However, how the anagen hair follicle specifies its size remains elusive. Here, we showed that in response to prolonged ectopic Wnt10b-mediated β-catenin activation, regenerating anagen hair follicles grew larger in size. In particular, the hair bulb, dermal papilla and hair shaft became enlarged, while the formation of different hair types (Guard, Awl, Auchene and Zigzag) was unaffected. Interestingly, we found that the effect of exogenous WNT10b was mainly on Zigzag and less on the other kinds of hairs. We observed dramatically enhanced proliferation within the matrix, DP and hair shaft of the enlarged AdWnt10b-treated hair follicles compared with those of normal hair follicles at P98. Furthermore, expression of CD34, a specific hair stem cell marker, was increased in its number to the bulge region after AdWnt10b treatment. Ectopic expression of CD34 throughout the ORS region was also observed. Many CD34-positive hair stem cells were actively proliferating in AdWnt10b-induced hair follicles. Importantly, subsequent co-treatment with the Wnt inhibitor, DKK1, reduced hair follicle enlargement and decreased proliferation and ectopic localization of hair stem cells. Moreover, injection of DKK1 during early anagen significantly reduced the width of prospective hairs. Together, these findings strongly suggest that Wnt10b/DKK1 can modulate hair follicle size during hair regeneration.

  12. Promoted growth of murine hair follicles through controlled release of vascular endothelial growth factor.

    PubMed

    Ozeki, Makoto; Tabata, Yasuhiko

    2002-06-01

    The objective of this study is to investigate whether or not the controlled release of vascular endothelial growth factor (VEGF) is effective in promoting the hair follicle growth of mice in second anagen of hair cycle. VEGF was incorporated into a biodegradable collagen hydrogel for its controlled release. Following implantation of the collagen hydrogel incorporating 0 or 2 microg of VEGF and injection of 0 or 2 microg of VEGF in the solution form into the back subcutis of mice, the hair follicle growth was evaluated photometrically and histologically in terms of the skin color of reverse side of the implanted or injected site, the skin thickness, and the area occupied by hair follicle tissue. Ten days later, the skin color of mice implanted with the collagen hydrogel incorporating 2 microg of VEGF was significantly darker than that injected with 2 pg of VEGF. The collagen hydrogel incorporating VEGF increased the hair follicle area at the implanted site to a significantly greater extent than other agents while significant angiogenetic effect in the skin tissue was observed. VEGF-free, empty collagen hydrogels did not affect the skin darkness, hair follicle growth, and the angiogenesis. Moreover, the hair shaft length was significantly elongated by the collagen hydrogel incorporating VEGF, in marked contrast to other agents. Immunohistolchemicalstaining with proliferating cell nuclear antigen revealed that the collagen hydrogel incorporating VEGF promoted the proliferation of cells around the hair follicle more frequently than free VEGF. We concluded that the controlled release of VEGF more positively acted on the hair growth cycle of mice for hair growth than the injection of free VEGF.

  13. Characterization and quantification of wound-induced hair follicle neogenesis using in vivo confocal scanning laser microscopy

    PubMed Central

    Fan, Chengxiang; Luedtke, Michael A.; Prouty, Stephen M.; Burrows, Michelle; Kollias, Nikiforos

    2011-01-01

    Background In vivo confocal scanning laser microscopy (CSLM) is a recently-developed non-invasive technique for visualizing microscopic structures with the skin. CSLM has been used to characterize proliferative and inflammatory skin diseases, neoplastic skin lesions and pigmented lesions. Objective Here, we assessed the ability of CSLM to evaluate the formation of neogenic hair follicles after a full thickness wound in mice. Methods Full-thickness wounds were made on the dorsal skin of 3-week old mice. After scab detachment (SD), the number, width, length, space and volume of neogenic hair follicles were analyzed using CSLM. The results were compared with those from conventional methods, including staining for alkaline phosphatase (AP) and keratin 17 (K17) as well as histology. Results Quantification of neogenic hair follicles using CSLM compared favorably with results from direct measurements on isolated epidermal tissue after immunostaining for K17, a marker for the epithelial portion of new hair follicles. CSLM detected 89% of K17-stained follicles. CSLM more accurately quantitated the number of new follicles compared to AP staining, which detects the dermal portion of the new follicle. The width and length measurement from CSLM and histology were very close and correlated with each other. The minimum length of a neogenic hair follicle that could be detected by CSLM was 21 μm. The space between neogenic hair follicles was decreased in histological sections compared to CSLM. Conclusions CSLM is an accurate and valuable method for counting and measuring neogenic hair follicles non-invasively. CSLM produces images similar to histology in mice. Measurements of microstructures using CSLM more accurately reflect actual sizes since this technique avoids fixation artifact. In vivo visualization of developing follicles with CSLM permits detection of serial changes in hair follicle formation, thus conserving numbers of mice required for studies and improving detection of

  14. Epidermal Wnt controls hair follicle induction by orchestrating dynamic signaling crosstalk between the epidermis and dermis.

    PubMed

    Fu, Jiang; Hsu, Wei

    2013-04-01

    A signal first arising in the dermis to initiate the development of hair follicles has been described for many decades. Wnt is the earliest signal known to be intimately involved in hair follicle induction. However, it is not clear whether the inductive signal of Wnt arises intradermally or intraepidermally. Whether Wnt acts as the first dermal signal to initiate hair follicle development also remains unclear. Here we report that Wnt production mediated by Gpr177, the mouse Wls ortholog, is essential for hair follicle induction. Gpr177, encoding a multipass transmembrane protein, regulates Wnt sorting and secretion. Cell type-specific abrogation of the signal reveals that only epidermal, but not dermal, production of Wnt is required. An intraepidermal Wnt signal is necessary and sufficient for hair follicle initiation. However, the subsequent development depends on reciprocal signaling crosstalk of epidermal and dermal cells. Wnt signals within the epidermis and dermis and crossing between the epidermis and dermis have distinct roles and specific functions in skin development. This study not only defines the cell type responsible for Wnt production, but also reveals a highly dynamic regulation of Wnt signaling at different steps of hair follicle morphogenesis. Our findings uncover a mechanism underlying hair follicle development orchestrated by the Wnt pathway.

  15. Runx1 modulates developmental, but not injury-driven, hair follicle stem cell activation.

    PubMed

    Osorio, Karen M; Lee, Song Eun; McDermitt, David J; Waghmare, Sanjeev K; Zhang, Ying V; Woo, Hyun Nyun; Tumbar, Tudorita

    2008-03-01

    Aml1/Runx1 controls developmental aspects of several tissues, is a master regulator of blood stem cells, and plays a role in leukemia. However, it is unclear whether it functions in tissue stem cells other than blood. Here, we have investigated the role of Runx1 in mouse hair follicle stem cells by conditional ablation in epithelial cells. Runx1 disruption affects hair follicle stem cell activation, but not their maintenance, proliferation or differentiation potential. Adult mutant mice exhibit impaired de novo production of hair shafts and all temporary hair cell lineages, owing to a prolonged quiescent phase of the first hair cycle. The lag of stem cell activity is reversed by skin injury. Our work suggests a degree of functional overlap in Runx1 regulation of blood and hair follicle stem cells at an equivalent time point in the development of these two tissues.

  16. Profiling the response of human hair follicles to ultraviolet radiation.

    PubMed

    Lu, Zhongfa; Fischer, Tobias W; Hasse, Sybille; Sugawara, Koji; Kamenisch, York; Krengel, Sven; Funk, Wolfgang; Berneburg, Mark; Paus, Ralf

    2009-07-01

    Excessive UVR ranks among the most harmful environmental influences on human skin. However, the direct impact of UVR on human skin appendages remains to be systematically investigated. Organ-cultured human anagen hair follicles in vitro were irradiated, and reduction of hair shaft elongation, premature catagen entry, and reduced hair matrix keratinocyte proliferation were observed upon irradiation with UVB (20/50 mJ cm(-2)). At 20 mJ cm(-2), apoptotic cell death prevailed (casp-3/p53 activation), whereas at 50 mJ cm(-2), necrotic cell death was predominant (lactate dehydrogenase increase). Mitochondrial common deletion and oxidatively damaged genomic DNA (8-OH-dG) was mainly observed at 20 mJ cm(-2). Follicular melanogenesis and ACTH immunoreactivity drastically declined, but alpha-melanocyte-stimulating hormone remained unchanged, whereas transforming growth factor-beta(2) expression shifted from the outer toward the inner root sheath. Both the number of Giemsa+ mast cells and the degree of mast-cell degranulation increased in the connective tissue sheath (CTS), and CD117 immunoreactivity of CTS cells and matrix keratinocytes was upregulated. Thus, UVR differentially modifies hair growth and cycle, promotes cell death, and induces complex regulatory events in human hair follicles in vitro. The leads from this human organ model, which is a living and human tissue interaction system under physiologically relevant in situ conditions, may encourage its use for general investigation of UV-induced effects as well as for testing possible agents for their UV-protective potency.

  17. An Essential Role for Dermal Primary Cilia in Hair Follicle Morphogenesis

    PubMed Central

    Lehman, Jonathan; Laag, Essam; Michaud, Edward J.; Yoder, Bradley K.

    2009-01-01

    The primary cilium is a microtubule-based organelle implicated as an essential component of a number of signaling pathways. It is present on cells throughout the mammalian body; however, its functions in most tissues remain largely unknown. Herein we demonstrate that primary cilia are present on cells in murine skin and hair follicles throughout morphogenesis and during hair follicle cycling in postnatal life. Using the Cre-lox system, we disrupted cilia assembly in the ventral dermis and evaluated the effects on hair follicle development. Mice with disrupted dermal cilia have severe hypotrichosis (lack of hair) in affected areas. Histological analyses reveal that most follicles in the mutants arrest at stage 2 of hair development and have small or absent dermal condensates. This phenotype is reminiscent of that seen in the skin of mice lacking Shh or Gli2. In situ hybridization and quantitative RT-PCR analysis indicates that the hedgehog pathway is downregulated in the dermis of the cilia mutant hair follicles. Thus, these data establish cilia as a critical signaling component required for normal hair morphogenesis and suggest that this organelle is needed on cells in the dermis for reception of signals such as sonic hedgehog. PMID:18987668

  18. Introduction to Hair-Follicle-Associated Pluripotent Stem Cells.

    PubMed

    Hoffman, Robert M

    2016-01-01

    Nestin-expressing stem cells of the hair follicle, discovered by our laboratory, have been shown to be able to form outer-root sheaths of the follicle as well as neurons and many other non-follicle cell types. We have termed the nestin-expressing stem cells of the hair follicle as hair-follicle-associated pluripotent (HAP) stem cells. We have shown that the HAP stem cells from the hair follicle can effect the repair of peripheral nerve and spinal cord injury. The hair follicle stem cells differentiate into neuronal and glial cells after transplantation to the injured peripheral nerve and spinal cord, and enhance injury repair and locomotor recovery. When the excised hair follicle with its nerve stump was placed in Gelfoam(®) 3D histoculture, HAP stem cells grew and extended the hair follicle nerve which consisted of βIII-tubulin-positive fibers with F-actin expression at the tip. These findings indicate that βIII-tubulin-positive fibers elongating from the whisker follicle sensory nerve stump were growing axons. The growing whisker sensory nerve was highly enriched in HAP stem cells, which appeared to play a major role in its elongation and interaction with other nerves in 3D Gelfoam(®) histoculture, including the sciatic nerve, the trigeminal nerve, and the trigeminal nerve ganglion. These results suggest that a major function of the HAP stem cells in the hair follicle is for growth of the follicle sensory nerve. Recently, we have shown that HAP stem cells can differentiate into beating cardiac muscle cells. HAP stem cells have critical advantages for regenerative medicine over embryonic stem (ES) cells and induced pluripotent stem (iPS) cells in that they are highly accessible from each patient, thereby eliminating immunological issues since they are autologous, require no genetic manipulation, are non-tumorigenic, and do not present ethical issues.

  19. Secrets of the Hair Follicle: Now on Your iPhone.

    PubMed

    Millar, Sarah E

    2015-09-14

    Skin development requires communication between epithelial and mesenchymal cells, melanocytes, and neurons. In this issue of Developmental Cell, Sennett et al. (2015) shed new light on these mechanisms by simultaneously profiling multiple different cell types in embryonic mouse skin at the onset of hair follicle formation.

  20. Mast cells as modulators of hair follicle cycling.

    PubMed

    Maurer, M; Paus, R; Czarnetzki, B M

    1995-08-01

    While the central role of mast cells (MC) in allergy and inflammation is well-appreciated, much less is known about their physiological functions. The impressive battery of potent growth modulatory MC products, and increasing evidence of MC involvement in hyperproliferative and fibrotic disorders suggest that tissue remodelling may be one of those, namely in the skin. Here, we delineate why this may best be studied by analysing the potential role of MC in hair growth regulation. On the background of numerous, yet widely under-appreciated hints from the older literature, we summarize and discuss our recent observations from the C57BL/6 mouse model for hair research which support the concept that MC are functionally important modulators of hair follicle cycling, specifically during anagen development. This invites to exploit the murine hair cycle as a model for dissecting the physiological growth modulatory functions of MC and encourages the exploration of MC-targeting pharmaceutical strategies for the treatment of hair growth disorders.

  1. Conditional telomerase induction causes proliferation of hair follicle stem cells

    PubMed Central

    Sarin, Kavita Y.; Cheung, Peggie; Gilison, Daniel; Lee, Eunice; Tennen, Ruth I.; Wang, Estee; Artandi, Maja K.; Oro, Anthony E.; Artandi, Steven E.

    2005-01-01

    TERT, the protein component of telomerase1,2, serves to maintain telomere function through the de novo addition of telomere repeats to chromosome ends and is reactivated in 90% of human cancers. In normal tissues, TERT is expressed in stem cells and in progenitor cells3, but its role in these compartments is not fully understood. Here, we show that conditional transgenic induction of TERT in mouse skin epithelium causes a rapid transition from telogen, the resting phase of the hair follicle cycle, to anagen, the active phase, thereby facilitating robust hair growth. TERT overexpression promotes this developmental transition by causing proliferation of quiescent, multipotent stem cells in the hair follicle bulge region. This new function for TERT does not require the telomerase RNA component (TERC), which encodes the template for telomere addition, and therefore operates through a novel mechanism independent of its activity in synthesizing telomere repeats. These data indicate that, in addition to its established role in extending telomeres, TERT can promote proliferation of resting stem cells through a non-canonical pathway. PMID:16107853

  2. Paracrine Secreted Frizzled-Related Protein 4 Inhibits Melanocytes Differentiation in Hair Follicle

    PubMed Central

    Guo, Haiying; Lei, Mingxing; Li, Yuhong; Liu, Yingxin; Tang, Yinhong; Xing, Yizhan; Deng, Fang

    2017-01-01

    Wnt signaling plays crucial role in regulating melanocyte stem cells/melanocyte differentiation in the hair follicle. However, how the Wnt signaling is balanced to be overactivated to control follicular melanocytes behavior remains unknown. Here, by using immunofluorescence staining, we showed that secreted frizzled-related protein 4 (sFRP4) is preferentially expressed in the skin epidermal cells rather than in melanocytes. By overexpression of sFRP4 in skin cells in vivo and in vitro, we found that sFRP4 attenuates activation of Wnt signaling, resulting in decrease of melanocytes differentiation in the regenerating hair follicle. Our findings unveiled a new regulator that involves modulating melanocytes differentiation through a paracrine mechanism in hair follicle, supplying a hope for potential therapeutic application to treat skin pigmentation disorders. PMID:28337220

  3. Growth of secondary hair follicles of the Cashmere goat in vitro and their response to prolactin and melatonin.

    PubMed Central

    Ibraheem, M; Galbraith, H; Scaife, J; Ewen, S

    1994-01-01

    The isolation and viability in vitro of anagen secondary hair follicles of the Cashmere goat were studied. Isolated hair follicles were used to determine the effects on hair shaft elongation, of prolactin and melatonin, hormones considered to influence hair follicle growth and activity in vivo. Intact hair follicles were isolated from the dermal layer of the skin singly or in groups using watchmakers' forceps under a dissecting microscope. The isolated follicles were maintained floating in Williams E medium. The medium was supplemented with 1 of 6 concentrations of ovine prolactin (0, 50, 200, 400, 800 and 4000 micrograms/l) for the culture of hair follicles isolated during July and August, and with 1 of 5 concentrations of melatonin (0, 50, 150, 300, 600 ng/l) for the culture of hair follicles isolated during September and October. There was clear evidence of DNA synthesis, observed by autoradiography, in matrix cells of freshly isolated follicles incubated for 6 h in the presence of [methyl-3H]-thymidine. Similar measurements after 96 h of maintenance indicated a marked reduction in the incorporation of [methyl-3H]-thymidine in matrix cells of the follicles studied. Prolactin and melatonin were shown to have a stimulating effect on hair shaft elongation of secondary follicles during 24 h periods of measurement and cumulatively over 120 h. Maximum hair follicle growth was observed in follicles exposed to 400 micrograms/l of prolactin and follicles exposed to 300 ng/l of melatonin. The number of follicles remaining viable during each 24 h measuring period was not affected by prolactin, but was significantly reduced by melatonin treatment after 96 h of maintenance.(ABSTRACT TRUNCATED AT 250 WORDS) Images Fig. 1 Fig. 2 Fig. 3 PMID:7559108

  4. Genetically null mice reveal a central role for epidermal growth factor receptor in the differentiation of the hair follicle and normal hair development.

    PubMed Central

    Hansen, L. A.; Alexander, N.; Hogan, M. E.; Sundberg, J. P.; Dlugosz, A.; Threadgill, D. W.; Magnuson, T.; Yuspa, S. H.

    1997-01-01

    Mice harboring a targeted disruption of the epidermal growth factor receptor (EGFR) allele exhibit a severely disorganized hair follicle phenotype, fuzzy coat, and systemic disease resulting in death before 3 weeks. This skin phenotype was reproduced in whole skin grafts and in grafts of EGFR null hair follicle buds onto nude mice, providing a model to evaluate the natural evolution of skin lacking the EGFR. Hair follicles in grafts of null skin did not progress from anagen to telogen and scanning electron micrografts revealed wavy, flattened hair fibers with cuticular abnormalities. Many of the EGFR null hair follicles in the grafted skin were consumed by an inflammatory reaction resulting in complete hair loss in 67% of the grafts by 10 weeks. Localization of follicular differentiation markers including keratin 6, transglutaminase, and the hair keratins mHa2 and hacl-1 revealed a pattern of premature differentiation within the null hair follicles. In intact EGFR null mice, proliferation in the interfollicular epidermis, but not hair follicles, was greatly decreased in the absence of EGFR. In contrast, grafting of EGFR null skin resulted in a hyperplastic response in the epidermis that did not resolve even after 10 weeks, although the wound-induced hyperplasia in EGFR wild-type grafts had resolved within 3 to 4 weeks. Thus, epithelial expression of the EGFR has complex functions in the skin. It is important in delaying follicular differentiation, may serve to protect the hair follicle from immunological reactions, and modifies both normal and wound-induced epidermal proliferation but seems dispensable for follicular proliferation. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 PMID:9176390

  5. Macrophages Contribute to the Cyclic Activation of Adult Hair Follicle Stem Cells

    PubMed Central

    Castellana, Donatello; Paus, Ralf; Perez-Moreno, Mirna

    2014-01-01

    Skin epithelial stem cells operate within a complex signaling milieu that orchestrates their lifetime regenerative properties. The question of whether and how immune cells impact on these stem cells within their niche is not well understood. Here we show that skin-resident macrophages decrease in number because of apoptosis before the onset of epithelial hair follicle stem cell activation during the murine hair cycle. This process is linked to distinct gene expression, including Wnt transcription. Interestingly, by mimicking this event through the selective induction of macrophage apoptosis in early telogen, we identify a novel involvement of macrophages in stem cell activation in vivo. Importantly, the macrophage-specific pharmacological inhibition of Wnt production delays hair follicle growth. Thus, perifollicular macrophages contribute to the activation of skin epithelial stem cells as a novel, additional cue that regulates their regenerative activity. This finding may have translational implications for skin repair, inflammatory skin diseases and cancer. PMID:25536657

  6. Decoction and Fermentation of Selected Medicinal Herbs Promote Hair Regrowth by Inducing Hair Follicle Growth in Conjunction with Wnts Signaling

    PubMed Central

    Jang, Su Kil; Kim, Seung Tae; Lee, Do Ik; Park, Jun Sub; Jo, Bo Ram; Park, Jung Youl; Heo, Jong; Joo, Seong Soo

    2016-01-01

    It is well recognized that regulating the hair follicle cycle in association with Wnt signaling is one of the most interesting targets for promoting hair regrowth. In this study, we examined whether selected herbal medicines processed by decoction and fermentation promote hair growth by upregulating the number and size of hair follicles and Wnt signaling, including activation of β-catenin and Akt in telogen-synchronized C57BL/6N mice. The results revealed that the fermented extract after decoction (FDE) more effectively promoted hair growth than that of a nonfermented extract (DE). Notably, FDE effectively enhanced formation of hair follicles with clearer differentiation between the inner and outer root sheath, which is observed during the anagen phase. Mechanistic evidence was found for increased β-catenin and Akt phosphorylation levels in dorsal skin tissue along with elevated expression of hair regrowth-related genes, such as Wnt3/10a/10b, Lef1, and fibroblast growth factor 7. In conclusion, our findings suggest that FDE plays an important role in regulating the hair cycle by increasing expression of hair regrowth-related genes and activating downstream Wnt signaling targets. PMID:27110266

  7. Decoction and Fermentation of Selected Medicinal Herbs Promote Hair Regrowth by Inducing Hair Follicle Growth in Conjunction with Wnts Signaling.

    PubMed

    Jang, Su Kil; Kim, Seung Tae; Lee, Do Ik; Park, Jun Sub; Jo, Bo Ram; Park, Jung Youl; Heo, Jong; Joo, Seong Soo

    2016-01-01

    It is well recognized that regulating the hair follicle cycle in association with Wnt signaling is one of the most interesting targets for promoting hair regrowth. In this study, we examined whether selected herbal medicines processed by decoction and fermentation promote hair growth by upregulating the number and size of hair follicles and Wnt signaling, including activation of β-catenin and Akt in telogen-synchronized C57BL/6N mice. The results revealed that the fermented extract after decoction (FDE) more effectively promoted hair growth than that of a nonfermented extract (DE). Notably, FDE effectively enhanced formation of hair follicles with clearer differentiation between the inner and outer root sheath, which is observed during the anagen phase. Mechanistic evidence was found for increased β-catenin and Akt phosphorylation levels in dorsal skin tissue along with elevated expression of hair regrowth-related genes, such as Wnt3/10a/10b, Lef1, and fibroblast growth factor 7. In conclusion, our findings suggest that FDE plays an important role in regulating the hair cycle by increasing expression of hair regrowth-related genes and activating downstream Wnt signaling targets.

  8. Foxp1 maintains hair follicle stem cell quiescence through regulation of Fgf18

    PubMed Central

    Leishman, Erin; Howard, Jeffrey M.; Garcia, Gloria E.; Miao, Qi; Ku, Amy T.; Dekker, Joseph D.; Tucker, Haley; Nguyen, Hoang

    2013-01-01

    Hair follicles cyclically degenerate and regenerate throughout adult life and require regular stem cell activation to drive the cycle. In the resting phase of the hair cycle, hair follicle stem cells are maintained in a quiescent state until they receive signals to proliferate. We found that the forkhead transcription factor Foxp1 is crucial for maintaining the quiescence of hair follicle stem cells. Loss of Foxp1 in skin epithelial cells leads to precocious stem cell activation, resulting in drastic shortening of the quiescent phase of the hair cycle. Conversely, overexpression of Foxp1 in keratinocytes prevents cell proliferation by promoting cell cycle arrest. Finally, through both gain- and loss-of-function studies, we identify fibroblast growth factor 18 (Fgf18) as the key downstream target of Foxp1. We show that exogenously supplied FGF18 can prevent the hair follicle stem cells of Foxp1 null mice from being prematurely activated. As Fgf18 controls the length of the quiescent phase and is a key downstream target of Foxp1, our data strongly suggest that Foxp1 regulates the quiescent stem cell state in the hair follicle stem cell niche by controlling Fgf18 expression. PMID:23946441

  9. De novo formation and ultra-structural characterization of a fiber-producing human hair follicle equivalent in vitro.

    PubMed

    Lindner, Gerd; Horland, Reyk; Wagner, Ilka; Ataç, Beren; Lauster, Roland

    2011-03-20

    Across many tissues and organs, the ability to create an organoid, the smallest functional unit of an organ, in vitro is the key both to tissue engineering and preclinical testing regimes. The hair follicle is an organoid that has been much studied based on its ability to grow quickly and to regenerate after trauma. But hair follicle formation in vitro has been elusive. Replacing hair lost due to pattern baldness or more severe alopecia, including that induced by chemotherapy, remains a significant unmet medical need. By carefully analyzing and recapitulating the growth conditions of hair follicle formation, we recreated human hair follicles in tissue culture that were capable of producing hair. Our microfollicles contained all relevant cell types and their structure and orientation resembled in some ways excised hair follicle specimens from human skin. This finding offers a new window onto hair follicle development. Having a robust culture system for hair follicles is an important step towards improved hair regeneration as well as to an understanding of how marketed drugs or drug candidates, including cancer chemotherapy, will affect this important organ.

  10. Spatial Distribution of Stem Cell-Like Keratinocytes in Dissected Compound Hair Follicles of the Dog

    PubMed Central

    Wiener, Dominique J.; Doherr, Marcus G.; Müller, Eliane J.; Welle, Monika M.

    2016-01-01

    Hair cycle disturbances are common in dogs and comparable to some alopecic disorders in humans. A normal hair cycle is maintained by follicular stem cells which are predominately found in an area known as the bulge. Due to similar morphological characteristics of the bulge area in humans and dogs, the shared particularity of compound hair follicles as well as similarities in follicular biomarker expression, the dog is a promising model to study human hair cycle and stem cell disorders. To gain insight into the spatial distribution of follicular keratinocytes with stem cell potential in canine compound follicles, we microdissected hair follicles in anagen and telogen from skin samples of freshly euthanized dogs. The keratinocytes isolated from different locations were investigated for their colony forming efficiency, growth and differentiation potential as well as clonal growth. Our results indicate that i) compound and single hair follicles exhibit a comparable spatial distribution pattern with respect to cells with high growth potential and stem cell-like characteristics, ii) the lower isthmus (comprising the bulge) harbors most cells with high growth potential in both, the anagen and the telogen hair cycle stage, iii) unlike in other species, colonies with highest growth potential are rather small with an irregular perimeter and iv) the keratinocytes derived from the bulbar region exhibit characteristics of actively dividing transit amplifying cells. Our results now provide the basis to conduct comparative studies of normal dogs and those with hair cycle disorders with the possibility to extend relevant findings to human patients. PMID:26788850

  11. Targeted delivery of a poorly water-soluble compound to hair follicles using polymeric nanoparticle suspensions.

    PubMed

    Morgen, Michael; Lu, Guang Wei; Du, Daniel; Stehle, Randall; Lembke, Franz; Cervantes, Jessica; Ciotti, Susan; Haskell, Roy; Smithey, Dan; Haley, Kevin; Fan, Conglin

    2011-09-15

    This study explored the utility of topically applied polymeric nanoparticle suspensions to target delivery of poorly water-soluble drugs to hair follicles. Several formulations of amorphous drug/polymer nanoparticles were prepared from ethyl cellulose and UK-157,147 (systematic name (3S,4R)-[6-(3-hydroxyphenyl)sulfonyl]-2,2,3-trimethyl-4-(2-methyl-3-oxo-2,3-dihydropyridazin-6-yloxy)-3-chromanol), a potassium channel opener, using sodium glycocholate (NaGC) as a surface stabilizer. Nanoparticle suspensions were evaluated to determine if targeted drug delivery to sebaceous glands and hair follicles could be achieved. In in vitro testing with rabbit ear tissue, delivery of UK-157,147 to the follicles was demonstrated with limited distribution to the surrounding dermis. Delivery to hair follicles was also demonstrated in vivo, based on stimulation of hair growth in tests of 100-nm nanoparticles with a C3H mouse model. The nanoparticles were well-tolerated, with no visible skin irritation. In vivo tests of smaller nanoparticles with a hamster ear model also indicated targeted delivery to sebaceous glands. The nanoparticles released drug rapidly in in vitro nonsink dissolution tests and were stable in suspension for 3 months. The present results show selective drug delivery to the follicle by follicular transport of nanoparticles and rapid release of a poorly water-soluble drug. Thus, nanoparticles represent a promising approach for targeted topical delivery of low-solubility compounds to hair follicles.

  12. Polymeric nanoparticles-embedded organogel for roxithromycin delivery to hair follicles.

    PubMed

    Główka, Eliza; Wosicka-Frąckowiak, Hanna; Hyla, Kinga; Stefanowska, Justyna; Jastrzębska, Katarzyna; Klapiszewski, Łukasz; Jesionowski, Teofil; Cal, Krzysztof

    2014-09-01

    Drug delivery into hair follicles with the use of nanoparticles (NPs) is gaining more importance as drug-loaded NPs may accumulate in hair follicle openings. The aim was to develop and evaluate a pluronic lecithin organogel (PLO) with roxithromycin (ROX)-loaded NPs for follicular targeting. Polymeric NPs were evaluated in terms of particle shape, size, zeta potential, suspension stability, encapsulation efficiency and in vitro drug release. Lyophilized NPs were incorporated into the PLO and rheological measurements of the nanoparticles-embedded organogels were done. The fate of the NPs in the skin was traced by incorporation of a fluorescent dye into the NPs. As a result, ROX was efficiently incorporated into polymeric NPs characterized by the appropriate size (approximately 300 nm) allowing drug delivery to hair follicles. In ex vivo human skin penetration studies, horizontal skin sections revealed fluorescence deep in the hair follicles. Although the organogel has higher affinity to the lipidic follicular area than an aqueous suspension of NPs, it did not seem to improve penetration of the NPs along the hair shaft. The results proved that it was possible to achieve preferential targeting to the pilosebaceous unit using polymeric NPs formulated either into the aqueous suspension or semisolid topical formulation.

  13. Contribution of the Hair Follicular Pathway to Total Skin Permeation of Topically Applied and Exposed Chemicals.

    PubMed

    Mohd, Fadli; Todo, Hiroaki; Yoshimoto, Masato; Yusuf, Eddy; Sugibayashi, Kenji

    2016-11-15

    Generally, the blood and skin concentration profiles and steady-state skin concentration of topically applied or exposed chemicals can be calculated from the in vitro skin permeation profile. However, these calculation methods are particularly applicable to chemicals for which the main pathway is via the stratum corneum. If the contribution of hair follicles to the total skin permeation of chemicals can be obtained in detail, their blood and skin concentrations can be more precisely predicted. In the present study, the contribution of the hair follicle pathway to the skin permeation of topically applied or exposed chemicals was calculated from the difference between their permeability coefficients through skin with and without hair follicle plugging, using an in vitro skin permeation experiment. The obtained results reveal that the contribution of the hair follicle pathway can be predicted by using the chemicals' lipophilicity. For hydrophilic chemicals (logarithm of n-octanol/water partition coefficient (log Ko/w) < 0), a greater reduction of permeation due to hair follicle plugging was observed than for lipophilic chemicals (log Ko/w ≥ 0). In addition, the ratio of this reduction was decreased with an increase in log Ko/w. This consideration of the hair follicle pathway would be helpful to investigate the efficacy and safety of chemicals after topical application or exposure to them because skin permeation and disposition should vary among skins in different body sites due to differences in the density of hair follicles.

  14. Contribution of the Hair Follicular Pathway to Total Skin Permeation of Topically Applied and Exposed Chemicals

    PubMed Central

    Mohd, Fadli; Todo, Hiroaki; Yoshimoto, Masato; Yusuf, Eddy; Sugibayashi, Kenji

    2016-01-01

    Generally, the blood and skin concentration profiles and steady-state skin concentration of topically applied or exposed chemicals can be calculated from the in vitro skin permeation profile. However, these calculation methods are particularly applicable to chemicals for which the main pathway is via the stratum corneum. If the contribution of hair follicles to the total skin permeation of chemicals can be obtained in detail, their blood and skin concentrations can be more precisely predicted. In the present study, the contribution of the hair follicle pathway to the skin permeation of topically applied or exposed chemicals was calculated from the difference between their permeability coefficients through skin with and without hair follicle plugging, using an in vitro skin permeation experiment. The obtained results reveal that the contribution of the hair follicle pathway can be predicted by using the chemicals’ lipophilicity. For hydrophilic chemicals (logarithm of n-octanol/water partition coefficient (log Ko/w) < 0), a greater reduction of permeation due to hair follicle plugging was observed than for lipophilic chemicals (log Ko/w ≥ 0). In addition, the ratio of this reduction was decreased with an increase in log Ko/w. This consideration of the hair follicle pathway would be helpful to investigate the efficacy and safety of chemicals after topical application or exposure to them because skin permeation and disposition should vary among skins in different body sites due to differences in the density of hair follicles. PMID:27854289

  15. Hair follicle changes following intense pulsed light axillary hair reduction: histometrical, histological and immunohistochemical evaluation.

    PubMed

    El-Domyati, Moetaz; Hosam, Wael; Moftah, Noha H; Abdel Raouf, Hamza; Saad, Selwet M

    2017-04-01

    Intense pulsed light (IPL) has been used for years in hair reduction; however, no previous studies discussed quantitative histological and immunohistochemical changes of hair follicles after IPL. Accordingly, this study aims to objectively quantify histological and immunohistochemical changes of hair follicles after IPL hair reduction. Right axillae of 21 volunteers were subjected to 6 IPL sessions using Quanta system IPL and evaluated at 1 week and 1 month after last session (i.e., 3 and 4 months from the start of treatment, respectively) in comparison to baseline and left control axillae. Using hair count, histological and immunohistochemical assessment of vertical and serial transverse sections coupled with computerized morphometric analysis, determination of hair reduction percentage, measurement of hair shaft (HS) diameter, calculation of percentage of hair follicle types and quantitative evaluation of PCNA, Ki67 and P53 markers were performed. After IPL, there was significant decrease of hair count, HS diameter, percentage of terminal anagen follicles, terminal/vellus (T/V) ratio, anagen/telogen (A/T) ratio and expression of PCNA and Ki67; however, significant increase of percentage of terminal telogen and total vellus follicles with vellus-like type and P53 expression was identified. So, reduction of hair number and thickness occurred after IPL by induction of telogenesis and miniaturization through decreased hair follicle proliferation and increase in DNA damage that could favor apoptosis.

  16. Keratin 15 promoter targets putative epithelial stem cells in the hair follicle bulge.

    PubMed

    Liu, Yaping; Lyle, Stephen; Yang, Zaixin; Cotsarelis, George

    2003-11-01

    Putative epithelial stem cells in the hair follicle bulge are thought to play pivotal roles in the homeostasis, aging, and carcinogenesis of the cutaneous epithelium. Elucidating the role of bulge cells in these processes has been hampered by the lack of gene promoters that target this area with specificity. Here we describe the isolation of the mouse keratin 15 (K15) promoter and demonstrate its utility for preferentially targeting hair follicle bulge cells in adult K15/lacZ transgenic mice. We found that patterns of K15 expression and promoter activity changed with age and correlated with levels of differentiation within the cutaneous epithelium; less differentiated keratinocytes in the epidermis of the neonatal mouse and in the bulge area of the adult mouse preferentially expressed K15. These findings demonstrate the utility of the K15 promoter for targeting epithelial stem cells in the hair follicle bulge and set the stage for elucidating the role of bulge cells in skin biology.

  17. Hormonal regulation of hair follicles exhibits a biological paradox.

    PubMed

    Randall, Valerie Anne

    2007-04-01

    Hair's importance for insulation and camouflage or human communication means that hairs need to change with season, age or sexual development. Regular, regenerating hair follicle growth cycles produce new hairs which may differ in colour and/or size, e.g., beard development. Hormones of the pineal-hypothalamus-pituitary axis coordinate seasonal changes, while androgens regulate most sexual aspects with paradoxically different effects depending on body site; compare beard growth and balding! Hormones affect follicular mesenchymal-epithelial interactions altering growing time, dermal papilla size and dermal papilla cell, keratinocyte and melanocyte activity. Greater understanding of these mechanisms should improve treatments for poorly controlled hair disorders, alopecia and hirsutism.

  18. The male beard hair and facial skin - challenges for shaving.

    PubMed

    Maurer, M; Rietzler, M; Burghardt, R; Siebenhaar, F

    2016-06-01

    The challenge of shaving is to cut the beard hair as closely as possible to the skin without unwanted effects on the skin. To achieve this requires the understanding of beard hair and male facial skin biology as both, the beard hair and the male facial skin, contribute to the difficulties in obtaining an effective shave without shaving-induced skin irritation. Little information is available on the biology of beard hairs and beard hair follicles. We know that, in beard hairs, the density, thickness, stiffness, as well as the rates of elliptical shape and low emerging angle, are high and highly heterogeneous. All of this makes it challenging to cut it, and shaving techniques commonly employed to overcome these challenges include shaving with increased pressure and multiple stroke shaving, which increase the probability and extent of shaving-induced skin irritation. Several features of male facial skin pose problems to a perfect shave. The male facial skin is heterogeneous in morphology and roughness, and male skin has a tendency to heal slower and to develop hyperinflammatory pigmentation. In addition, many males exhibit sensitive skin, with the face most often affected. Finally, the hair follicle is a sensory organ, and the perifollicular skin is highly responsive to external signals including mechanical and thermal stimulation. Perifollicular skin is rich in vasculature, innervation and cells of the innate and adaptive immune system. This makes perifollicular skin a highly responsive and inflammatory system, especially in individuals with sensitive skin. Activation of this system, by shaving, can result in shaving-induced skin irritation. Techniques commonly employed to avoid shaving-induced skin irritation include shaving with less pressure, pre- and post-shave skin treatment and to stop shaving altogether. Recent advances in shaving technology have addressed some but not all of these issues. A better understanding of beard hairs, beard hair follicles and male

  19. A genetic basis of variation in eccrine sweat gland and hair follicle density.

    PubMed

    Kamberov, Yana G; Karlsson, Elinor K; Kamberova, Gerda L; Lieberman, Daniel E; Sabeti, Pardis C; Morgan, Bruce A; Tabin, Clifford J

    2015-08-11

    Among the unique features of humans, one of the most salient is the ability to effectively cool the body during extreme prolonged activity through the evapotranspiration of water on the skin's surface. The evolution of this novel physiological ability required a dramatic increase in the density and distribution of eccrine sweat glands relative to other mammals and a concomitant reduction of body hair cover. Elucidation of the genetic underpinnings for these adaptive changes is confounded by a lack of knowledge about how eccrine gland fate and density are specified during development. Moreover, although reciprocal changes in hair cover and eccrine gland density are required for efficient thermoregulation, it is unclear if these changes are linked by a common genetic regulation. To identify pathways controlling the relative patterning of eccrine glands and hair follicles, we exploited natural variation in the density of these organs between different strains of mice. Quantitative trait locus mapping identified a large region on mouse Chromosome 1 that controls both hair and eccrine gland densities. Differential and allelic expression analysis of the genes within this interval coupled with subsequent functional studies demonstrated that the level of En1 activity directs the relative numbers of eccrine glands and hair follicles. These findings implicate En1 as a newly identified and reciprocal determinant of hair follicle and eccrine gland density and identify a pathway that could have contributed to the evolution of the unique features of human skin.

  20. Skin regeneration with conical and hair follicle structure of deep second-degree scalding injuries via combined expression of the EPO receptor and beta common receptor by local subcutaneous injection of nanosized rhEPO

    PubMed Central

    Bader, Augustinus; Ebert, Sabine; Giri, Shibashish; Kremer, Mathias; Liu, Shuhua; Nerlich, Andreas; Günter, Christina I; Smith, Dagmar U; Machens, Hans-Günther

    2012-01-01

    Background Acceleration of skin regeneration is still an unsolved problem in the clinical treatment of patients suffering from deep burns and scalds. Although erythropoietin (EPO) has a protective role in a wide range of organs and cells during ischemia and after trauma, it has been recently discovered that EPO is not tissue-protective in the common β subunit receptor (βCR) knockout mouse. The protective capacity of EPO in tissue is mediated via a heteroreceptor complex comprising both the erythropoietin receptor (EPOR) and βCR. However, proof of coexpression of these heterogenic receptors in regenerating skin after burns is still lacking. Methods To understand the role of nanosized recombinant human erythropoietin (rhEPO) in wound healing, we investigated the effects of subcutaneous injections of EPO on skin regeneration after deep second-degree scalding injuries. Our aim was to determine if joint expression of EPOR and βCR is a prerequisite for the tissue-protective effect of rhEPO. The efficiency in wound regeneration in a skin scalding injury mouse model was examined. A deep second-degree dermal scald injury was produced on the backs of 20 female Balb/c mice which were subsequently randomized to four experimental groups, two of which received daily subcutaneous injections of rhEPO. At days 7 and 14, the mice were sacrificed and the effects of rhEPO were analyzed with respect to grade of re-epithelialization (wound closure) and stage of epidermal maturation. This was investigated using different histological parameters of epithelial covering, such as depth of the epidermal layer, epidermal stratification, and presence of conical and hair follicle structures. Results Expression of EPOR, βCR, and growth hormone receptor at the mRNA and protein levels was demonstrated with reverse transcriptase polymerase chain reaction and Western blot analysis. After rhEPO treatment, the rate of re-epithelialization of the scalding injury was increased and the time to final

  1. Identification of cannabinoid type 1 receptor in dog hair follicles.

    PubMed

    Mercati, Francesca; Dall'Aglio, Cecilia; Pascucci, Luisa; Boiti, Cristiano; Ceccarelli, Piero

    2012-01-01

    In veterinary medicine, there is an increasing interest in the study of the endo-cannabinoid system and the possible use of the cannabinoids for the treatment of several diseases. Cannabinoid receptors (CB) are widely distributed in human and laboratory animal tissues, justifying the involvement of the endo-cannabinoid system in a great number of metabolic ways. Since there are no data regarding cannabinoid receptors in hair follicles of domestic animals, we investigated the presence and localization of CB1 receptor in dog hair follicles. By using a goat anti-CB1 polyclonal antibody, we observed CB1 receptor in the proximal part of both primary and secondary hair follicles. Staining was localized in the inner root sheath cells. We suppose that the endo-cannabinoid system is involved in the molecular mechanisms regulating hair follicle activity in dog. The identification of CB1 receptor at the level of the inner root sheath may help in the understanding of hair follicle biology and the possibility that cannabinoid molecules could be considered as suitable therapeutic tools in dog.

  2. Wls is expressed in the epidermis and regulates embryonic hair follicle induction in mice.

    PubMed

    Huang, Sixia; Zhu, Xuming; Liu, Yanfang; Tao, Yixin; Feng, Guoyin; He, Lin; Guo, Xizhi; Ma, Gang

    2012-01-01

    Wnt proteins are secreted molecules that play multiple roles during hair follicle development and postnatal hair cycling. Wntless (Wls) is a cargo protein required for the secretion of various Wnt ligands. However, its role during hair follicle development and hair cycling remains unclear. Here, we examined the expression of Wls during hair follicle induction and postnatal hair cycling. We also conditionally deleted Wls with K14-cre to investigate its role in hair follicle induction. K14-cre;Wls(c/c) mice exhibited abnormal hair follicle development, which is possibly caused by impaired canonical Wnt signaling. Meanwhile, Wnt5a is also expressed in embryonic epidermis, but Wnt5a null mice showed no significant defect in embryonic hair follicle morphogenesis. Therefore, Wls may regulate hair follicle induction by mediating the Wnt/β-catenin pathway.

  3. Targeted expression of GFP in the hair follicle using ex vivo viral transduction.

    PubMed

    Hoffman, Robert M; Li, Lingna

    2008-03-17

    There are many cell types in the hair follicle, including hair matrix cells which form the hair shaft and stem cells which can initiate the hair shaft during early anagen, the growth phase of the hair cycle, as well as pluripotent stem cells that play a role in hair follicle growth but have the potential to differentiate to non-follicle cells such as neurons. These properties of the hair follicle are discussed. The various cell types of the hair follicle are potential targets for gene therapy. Gene delivery system for the hair follicle using viral vectors or liposomes for gene targeting to the various cell types in the hair follicle and the results obtained are also discussed [corrected].

  4. Paracrine crosstalk between human hair follicle dermal papilla cells and microvascular endothelial cells.

    PubMed

    Bassino, Eleonora; Gasparri, Franco; Giannini, Valentina; Munaron, Luca

    2015-05-01

    Human follicle dermal papilla cells (FDPC) are a specialized population of mesenchymal cells located in the skin. They regulate hair follicle (HF) development and growth, and represent a reservoir of multipotent stem cells. Growing evidence supports the hypothesis that HF cycling is associated with vascular remodeling. Follicular keratinocytes release vascular endothelial growth factor (VEGF) that sustains perifollicular angiogenesis leading to an increase of follicle and hair size. Furthermore, several human diseases characterized by hair loss, including Androgenetic Alopecia, exhibit alterations of skin vasculature. However, the molecular mechanisms underlying HF vascularization remain largely unknown. In vitro coculture approaches can be successfully employed to greatly improve our knowledge and shed more light on this issue. Here we used Transwell-based co-cultures to show that FDPC promote survival, proliferation and tubulogenesis of human microvascular endothelial cells (HMVEC) more efficiently than fibroblasts. Accordingly, FDPC enhance the endothelial release of VEGF and IGF-1, two well-known proangiogenic growth factors. Collectively, our data suggest a key role of papilla cells in vascular remodeling of the hair follicle.

  5. Epidermal and hair follicle progenitor cells express melanoma-associated chondroitin sulfate proteoglycan core protein.

    PubMed

    Ghali, Lucy; Wong, Soon-Tee; Tidman, Nick; Quinn, Anthony; Philpott, Michael P; Leigh, Irene M

    2004-02-01

    Basal keratinocytes in the epidermis and hair follicle are biologically heterogeneous but must include a stable subpopulation of epidermal stem cells. In animal models these can be identified by their retention of radioactive label due to their slow cycle (label-retaining cells) but human studies largely depend on in vitro characterization of colony forming efficiency and clonogenicity. Differential integrin expression has been used to detect cells of increased proliferative potential but further stem cell markers are urgently required for in vivo and in vitro characterization. Using LHM2, a monoclonal antibody reacting with a high molecular weight melanoma-associated proteoglycan core protein, a subset of basal keratinocytes in both the interfollicular epidermis and the hair follicle has been identified. Coexpression of melanoma-associated chondroitin sulfate proteoglycan with keratins 15 and 19 as well as beta 1 and alpha 6 integrins has been examined in adult and fetal human skin from hair bearing, nonhair bearing, and palmoplantar regions. Although melanoma-associated chondroitin sulfate proteoglycan coexpression with a subset of beta 1 integrin bright basal keratinocytes within the epidermis suggests that melanoma-associated chondroitin sulfate proteoglycan colocalizes with epidermal stem cells, melanoma-associated chondroitin sulfate proteoglycan expression within the hair follicle was more complex and multiple subpopulations of basal outer root sheath keratinocytes are described. These data suggest that epithelial compartmentalization of the outer root sheath is more complex than interfollicular epidermis and further supports the hypothesis that more than one hair follicle stem cell compartment may exist.

  6. Isolation and culture of neural crest stem cells from human hair follicles.

    PubMed

    Yang, Ruifeng; Xu, Xiaowei

    2013-04-06

    Hair follicles undergo lifelong growth and hair cycle is a well-controlled process involving stem cell proliferation and quiescence. Hair bulge is a well-characterized niche for adult stem cells. This segment of the outer root sheath contains a number of different types of stem cells, including epithelial stem cells, melanocyte stem cells and neural crest like stem cells. Hair follicles represent an accessible and rich source for different types of human stem cells. We and others have isolated neural crest stem cells (NCSCs) from human fetal and adult hair follicles. These human stem cells are label-retaining cells and are capable of self-renewal through asymmetric cell division in vitro. They express immature neural crest cell markers but not differentiation markers. Our expression profiling study showed that they share a similar gene expression pattern with murine skin immature neural crest cells. They exhibit clonal multipotency that can give rise to myogenic, melanocytic, and neuronal cell lineages after in vitro clonal single cell culture. Differentiated cells not only acquire lineage-specific markers but also demonstrate appropriate functions in ex vivo conditions. In addition, these NCSCs show differentiation potential toward mesenchymal lineages. Differentiated neuronal cells can persist in mouse brain and retain neuronal differentiation markers. It has been shown that hair follicle derived NCSCs can help nerve regrowth, and they improve motor function in mice transplanted with these stem cells following transecting spinal cord injury. Furthermore, peripheral nerves have been repaired with stem cell grafts, and implantation of skin-derived precursor cells adjacent to crushed sciatic nerves has resulted in remyelination. Therefore, the hair follicle/skin derived NCSCs have already shown promising results for regenerative therapy in preclinical models. Somatic cell reprogramming to induced pluripotent stem (iPS) cells has shown enormous potential for

  7. The hair follicle as an estrogen target and source.

    PubMed

    Ohnemus, Ulrich; Uenalan, Murat; Inzunza, José; Gustafsson, Jan-Ake; Paus, Ralf

    2006-10-01

    For many decades, androgens have dominated endocrine research in hair growth control. Androgen metabolism and the androgen receptor currently are the key targets for systemic, pharmacological hair growth control in clinical medicine. However, it has long been known that estrogens also profoundly alter hair follicle growth and cycling by binding to locally expressed high-affinity estrogen receptors (ERs). Besides altering the transcription of genes with estrogen-responsive elements, 17beta-estradiol (E2) also modifies androgen metabolism within distinct subunits of the pilosebaceous unit (i.e., hair follicle and sebaceous gland). The latter displays prominent aromatase activity, the key enzyme for androgen conversion to E2, and is both an estrogen source and target. Here, we chart the recent renaissance of estrogen research in hair research; explain why the hair follicle offers an ideal, clinically relevant test system for studying the role of sex steroids, their receptors, and interactions in neuroectodermal-mesodermal interaction systems in general; and illustrate how it can be exploited to identify novel functions and signaling cross talks of ER-mediated signaling. Emphasizing the long-underestimated complexity and species-, gender-, and site-dependence of E2-induced biological effects on the hair follicle, we explore targets for pharmacological intervention in clinically relevant hair cycle manipulation, ranging from androgenetic alopecia and hirsutism via telogen effluvium to chemotherapy-induced alopecia. While defining major open questions, unsolved clinical challenges, and particularly promising research avenues in this area, we argue that the time has come to pay estrogen-mediated signaling the full attention it deserves in future endocrinological therapy of common hair growth disorders.

  8. 7-Phloroeckol promotes hair growth on human follicles in vitro.

    PubMed

    Bak, Soon-Sun; Sung, Young Kwan; Kim, Se-Kwon

    2014-08-01

    7-Phloroeckol, phloroglucinol derivative isolated from marine brown algae, has anti-oxidative, anti-inflammatory responses and MMP inhibitory activities. In this study, we evaluated the hair growth-promoting effects of 7-phloroeckol in human hair follicles. To investigate cell viability of human dermal papilla cells (DPCs) and outer root sheath (ORS) cells in the presence or absence of 7-phloroeckol treatment, MTT assay was employed. Moreover, gene expression and protein concentration of insulin-like growth factor (IGF)-1 was measured by reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay. 7-Phloroeckol induced an increase in proliferation of DPCs and ORS cells. In addition, hair shaft growth was measured using the hair-follicle organ culture system. 7-Phloroeckol resulted in elongation of the hair shaft in cultured human hair follicles. 7-Phloroeckol induced an IGF-1 mRNA expression and protein concentration in DPCs and conditioned media, respectively. These results suggest that 7-phloroeckol promotes hair growth through stimulation of DPCs and ORS cells.

  9. A genetic basis of variation in eccrine sweat gland and hair follicle density

    PubMed Central

    Kamberov, Yana G.; Karlsson, Elinor K.; Kamberova, Gerda L.; Lieberman, Daniel E.; Sabeti, Pardis C.; Morgan, Bruce A.; Tabin, Clifford J.

    2015-01-01

    Among the unique features of humans, one of the most salient is the ability to effectively cool the body during extreme prolonged activity through the evapotranspiration of water on the skin’s surface. The evolution of this novel physiological ability required a dramatic increase in the density and distribution of eccrine sweat glands relative to other mammals and a concomitant reduction of body hair cover. Elucidation of the genetic underpinnings for these adaptive changes is confounded by a lack of knowledge about how eccrine gland fate and density are specified during development. Moreover, although reciprocal changes in hair cover and eccrine gland density are required for efficient thermoregulation, it is unclear if these changes are linked by a common genetic regulation. To identify pathways controlling the relative patterning of eccrine glands and hair follicles, we exploited natural variation in the density of these organs between different strains of mice. Quantitative trait locus mapping identified a large region on mouse Chromosome 1 that controls both hair and eccrine gland densities. Differential and allelic expression analysis of the genes within this interval coupled with subsequent functional studies demonstrated that the level of En1 activity directs the relative numbers of eccrine glands and hair follicles. These findings implicate En1 as a newly identified and reciprocal determinant of hair follicle and eccrine gland density and identify a pathway that could have contributed to the evolution of the unique features of human skin. PMID:26195765

  10. Intelligent Image Analysis for Image-Guided Laser Hair Removal and Skin Therapy

    NASA Technical Reports Server (NTRS)

    Walker, Brian; Lu, Thomas; Chao, Tien-Hsin

    2012-01-01

    We present the development of advanced automatic target recognition (ATR) algorithms for the hair follicles identification in digital skin images to accurately direct the laser beam to remove the hair. The ATR system first performs a wavelet filtering to enhance the contrast of the hair features in the image. The system then extracts the unique features of the targets and sends the features to an Adaboost based classifier for training and recognition operations. The ATR system automatically classifies the hair, moles, or other skin lesion and provides the accurate coordinates of the intended hair follicle locations. The coordinates can be used to guide a scanning laser to focus energy only on the hair follicles. The intended benefit would be to protect the skin from unwanted laser exposure and to provide more effective skin therapy.

  11. Intelligent image analysis for image-guided hair removal and skin therapy

    NASA Astrophysics Data System (ADS)

    Walker, Brian; Lu, Thomas; Chao, Tien-Hsin

    2012-02-01

    We present the development of advanced automatic target recognition (ATR) algorithms for the hair follicles identification in digital skin images to accurately direct the laser beam to remove the hair. The ATR system first performs a wavelet filtering to enhance the contrast of the hair features in the image. The system then extracts the unique features of the targets and sends the features to an Adaboost based classifier for training and recognition operations. The ATR system automatically classifies the hair, moles, or other skin lesion and provides the accurate coordinates of the intended hair follicle locations. The coordinates can be used to guide a scanning laser to focus energy only on the hair follicles. The intended benefit would be to protect the skin from unwanted laser exposure and to provide more effective skin therapy.

  12. Aqueous extract of red deer antler promotes hair growth by regulating the hair cycle and cell proliferation in hair follicles.

    PubMed

    Li, Jing-jie; Li, Zheng; Gu, Li-juan; Wang, Yun-bo; Lee, Mi-ra; Sung, Chang-keun

    2014-01-01

    Deer antlers are the only mammalian appendage capable of regeneration. We aimed to investigate the effect of red deer antler extract in regulating hair growth, using a mouse model. The backs of male mice were shaved at eight weeks of age. Crude aqueous extracts of deer antler were prepared at either 4 °C or 100 °C and injected subcutaneously to two separate groups of mice (n = 9) at 1 mL/day for 10 consecutive days, with water as a vehicle control group. The mice skin quantitative hair growth parameters were measured and 5-bromo-2-deoxyuridine was used to identify label-retaining cells. We found that, in both the 4 °C and the 100 °C deer antler aqueous extract-injection groups, the anagen phase was extended, while the number of BrdU-incorporated cells was dramatically increased. These results indicate that deer antler aqueous extract promotes hair growth by extending the anagen phase and regulating cell proliferation in the hair follicle region.

  13. GMP-compliant culture of human hair follicle cells for encapsulation and transplantation.

    PubMed

    Marazzi, Mario; Crovato, Francesca; Bucco, Massimo; Sironi, Maria Chiara; Tosca, Marta Cecilia; Antonioli, Barbara; Chlapanidas, Theodora; Lucconi, Giulia; Rapisarda, Vincenzo; Scalise, Alessandro; Vigo, Daniele; Faustini, Massimo; Torre, Maria Luisa

    2012-01-01

    Human hair follicle cells, both bulge and dermal papilla cells, were isolated and cultured in a GMP cell factory, in order to obtain an in vitro hair follicle source for encapsulation end transplantation in alopecia regenerative cell therapy. An in vitro model, constituted by organotypic cultures of human skin sample, was set up to simulate the dermal-epidermal interaction between bulge cells and dermal papilla cells, evaluating the possible new follicles formation and the regenerative potentiality of these hair follicle cells. Both the bulge and dermal papilla cells show an excellent cellular proliferation as well as an abundant extracellular matrix production. The immunofluorescence investigation revealed the positivity of both cell lines to CK15 and CD200, whereas both cell lines were negative to CD71 and Oct-4. The pool of cultured bulge and dermal papilla cells was injected into the deep dermis; at day 28 of culture, some organized areas with a higher cell density can be observed: the cells self-organize into papilla-like lengthened aggregates. In samples in which the follicular cells have been seeded on the dermis surface, an epidermis-like homogeneous monolayer on the dermis surface can be seen, therefore showing a potentiality of these cells for epidermis regeneration. These data show the efficacy of a cellular isolation and amplification approach to obtain an in vitro human hair follicle regenerative source on industrial scale in a GMP cell factory. The results also proved an intrinsic potentiality of follicular cells to in vitro recreate the epidermis for tissue engineering purposes. Thus, it is feasible to produce bioengineered hair follicles in a GMP cell factory, for encapsulation and transplantation in alopecic patients.

  14. Organization and expression of hair follicle genes.

    PubMed

    Rogers, G E; Powell, B C

    1993-07-01

    Several families of proteins are expressed in the growth of hair and an estimated 50-100 proteins constitute the final hair fiber. The cumbersome nomenclature for naming these different proteins has led to a proposal to modify that which is currently used for epidermal keratins. Investigations of the organization of hair genes indicate that the members of each family are clustered in the genome and their expression could be under some general control. Interestingly, the protein called trichohyalin, markedly distinct from the hair proteins, is produced in the inner root sheath cells and the gene for it has been found to be located at the same human chromosome locus as the genes for profilaggrin, involucrin, and loricrin. A mainstream objective is to identify controls responsible for the production in the hair cortex of keratin intermediate filaments (IFs) and two large groups of keratin-associated proteins (KAPs) rich in the amino acids cysteine or glycine/tyrosine. A specific family of cysteine-rich proteins is expressed in the hair cuticle. Comparisons of promoter regions of IF genes and KAP genes, including a recently characterized gene for a glycine/tyrosine-rich protein, have revealed putative hair-specific motifs in addition to known elements that regulate gene expression. In the sheep, the patterns of expression in hair differentiation are particularly interesting insofar as there are distinct segments of para- and orthocortical type cells that have significantly different pathways of expression. The testing of candidate hair-specific regulatory sequences by mouse transgenesis has produced several interesting hair phenotypes. Transgenic sheep over-expressing keratin genes but showing no hair growth change have been obtained and compared with the equivalent transgenic hair-loss mice. Studies of the effects of amino acid supply on the rate of hair growth have demonstrated that with cysteine supplementation of sheep a perturbation occurs in which there is a

  15. Selective activation of the versican promoter by epithelial– mesenchymal interactions during hair follicle development

    PubMed Central

    Kishimoto, Jiro; Ehama, Ritsuko; Wu, Lin; Jiang, Shuwei; Jiang, Nanyan; Burgeson, Robert E.

    1999-01-01

    Interaction between the epithelium and the mesenchyme is an essential feature of organogenesis, including hair follicle formation. The dermal papilla (DP), a dense aggregate of specialized dermis-derived stromal cells located at the bottom of the follicle, is a major component of hair that signals the follicular epithelial cells to prolong the hair growth process. However, little is known about DP-specific gene activation with regard to hair induction. In this study we demonstrate that a short fragment (839 bp) of the human versican (a core protein of one of the matrix chondroitin sulfate proteoglycans) promoter is sufficient to activate lacZ reporter gene expression in the DP of postnatal transgenic mice and also in the condensed mesenchyme (the origin of the DP) beneath the hair placode during hair follicle embryogenesis. Using the same versican promoter with green fluorescent protein (GFP), large numbers of fresh pelage DP cells were isolated from newborn transgenic skin by high-speed cell sorting. These GFP-positive DP cells showed abundant versican mRNA, confirming that the reporter molecules reflected endogenous versican gene expression. These sorted GFP-positive cells showed DP-like morphology in culture, but both GFP and versican expression was lost during primary culture. In vivo hair growth assays showed that GFP-positive cells could induce hair when grafted with epithelial cells, whereas GFP-negative cells grafted with epithelium or GFP-positive cells alone did not. These results suggest that versican may play an essential role both in mesenchymal condensation and in hair induction. PMID:10377415

  16. Restorative effect of hair follicular dermal cells on injured human hair follicles in a mouse model.

    PubMed

    Yamao, Mikaru; Inamatsu, Mutsumi; Okada, Taro; Ogawa, Yuko; Ishida, Yuji; Tateno, Chise; Yoshizato, Katsutoshi

    2015-03-01

    No model is available for examining whether in vivo-damaged human hair follicles (hu-HFs) are rescued by transplanting cultured hu-HF dermal cells (dermal papilla and dermal sheath cells). Such a model might be valuable for examining whether in vivo-damaged hu-HFs such as miniaturized hu-HFs in androgenic alopecia are improvable by auto-transplanting hu-HF dermal cells. In this study, we first developed mice with humanized skin composed of hu-keratinocytes and hu-dermal fibroblasts. Then, a 'humanized scalp model mouse' was generated by transplanting hu-scalp HFs into the humanized skin. To demonstrate the usability of the model, the lower halves of the hu-HFs in the model were amputated in situ, and cultured hu-HF dermal cells were injected around the amputated area. The results demonstrated that the transplanted cells contributed to the restoration of the damaged HFs. This model could be used to explore clinically effective technologies for hair restoration therapy by autologous cell transplantation.

  17. Observing Cells in Plucked Hair Follicles.

    ERIC Educational Resources Information Center

    Wells, John

    1991-01-01

    A simple technique is described by which the cells attached to plucked hair can be observed and used to demonstrate dividing and differentiating cell populations. The necessary equipment and the procedure are listed. (Author/KR)

  18. Innovative modified hair follicle harvesting technique with reverse rake scalp elevator for lower occipital donor area in follicular unit extraction hair transplantation

    PubMed Central

    Gharwade, Chandrakant Rambhau

    2016-01-01

    Follicular unit extraction (FUE) is one of the widely practiced minimally invasive follicular harvesting techniques employed during hair transplantation. FUE technique has an advantage of utilising lower occipital area and supra-auricular region as a safe donor area described by Unger, in addition to the standard occipital donor area used in strip method (follicular unit transplant). Despite its potential advantages such as rapid recovery, minimal scarring and reduced post-operative pain; its widespread acceptance is limited due to various factors in variable contribution like steeper learning curve and potentially higher follicular transection rates (FTRs). The main practical drawbacks in harvesting FUE from lower occipital donor region that lie inferior to the standard donor area, is its acute angle (10°–15°) of emergent hair from scalp skin, higher variance angle (15°–35°) between hairs below the skin and hair exit angle above the skin and comparatively loose scalp, preventing to provide stable platform for punching. Hair transplant surgeon faces difficulty in aligning and engaging the FUE punch leading to very high hair follicle transection rate, and therefore, it is not a preferred site for harvesting follicles in FUE. Authors description of modified technique using reverse rake scalp elevator helps in negating the acute angle of the hair follicles exit from scalp skin and reducing the variance angle between emergent hair and hair below the skin in lower occipital region thereby reducing FTR. Furthermore, an added advantage of reducing the overall operative time and surgeon fatigue, improve donor area healing, availability of a comparatively larger donor area which increases the confidence of the beginners. This method will be of help as it is easy to duplicate and follow by novice hair transplant surgeons and also for those who are routinely doing mega hair transplants sessions. PMID:28216821

  19. Differential Expression of Proteins Associated with the Hair Follicle Cycle - Proteomics and Bioinformatics Analyses

    PubMed Central

    Tian, Tian; Yang, Mifang; Li, Zhongming; Ping, Fengfeng; Fan, Weixin

    2016-01-01

    Hair follicle cycling can be divided into the following three stages: anagen, catagen, and telogen. The molecular signals that orchestrate the follicular transition between phases are still unknown. To better understand the detailed protein networks controlling this process, proteomics and bioinformatics analyses were performed to construct comparative protein profiles of mouse skin at specific time points (0, 8, and 20 days). Ninety-five differentially expressed protein spots were identified by MALDI-TOF/TOF as 44 proteins, which were found to change during hair follicle cycle transition. Proteomics analysis revealed that these changes in protein expression are involved in Ca2+-regulated biological processes, migration, and regulation of signal transduction, among other processes. Subsequently, three proteins were selected to validate the reliability of expression patterns using western blotting. Cluster analysis revealed three expression patterns, and each pattern correlated with specific cell processes that occur during the hair cycle. Furthermore, bioinformatics analysis indicated that the differentially expressed proteins impacted multiple biological networks, after which detailed functional analyses were performed. Taken together, the above data may provide insight into the three stages of mouse hair follicle morphogenesis and provide a solid basis for potential therapeutic molecular targets for this hair disease. PMID:26752403

  20. Expression and localization of the vascular endothelial growth factor and changes of microvessel density during hair follicle development of Liaoning cashmere goats.

    PubMed

    Zhang, Q L; Li, J P; Li, Y M; Chang, Q; Chen, Y; Jiang, H Z; Zhao, Z H; Guo, D

    2013-12-10

    Vascular endothelial growth factors (VEGFs) play important roles in neovascularization, tissue development, and angiogenesis. In this study, changes in VEGF expression patterns and microvessel density (MVD), and their correlations, were investigated during hair follicle development in epidermal appendages of Liaoning cashmere goats. Polyclonal antibodies to VEGF and microvessels were used for monthly immunohistochemical examinations of normal skin specimens from adult female goats for one year. VEGF was expressed in the hair bulb of primary and secondary hair follicles, the outer and inner root sheaths, sebaceous glands (ductal and secretory portions), eccrine sweat glands (ductal and secretory portions), and the epidermis. Abundant expression of VEGF was observed in the follicular basement membrane zone surrounding the bulb matrix and in ductal and secretory portions of eccrine sweat glands. The change in VEGFs in primary hair follicles showed a bimodal pattern, with the first peak observed from March to May, and the second in August. Maximal expression in secondary hair follicles occurred in May and August. Therefore, VEGF expression in primary and secondary hair follicles is synchronized throughout the year, and is correlated to hair development. In the later telogen and anagen phases, VEGF expression was higher in the secondary, compared to the primary, hair follicle. Changes in MVD also showed a bimodal pattern with peaks in May and August. VEGF expression and MVD showed moderate and strongly positive correlation in the primary and secondary hair follicles, respectively. Therefore, MVD and VEGF are closely related to the processes involved in hair cycle regulation.

  1. Exogenous R-Spondin1 Induces Precocious Telogen-to-Anagen Transition in Mouse Hair Follicles

    PubMed Central

    Li, Na; Liu, Shu; Zhang, Hui-Shan; Deng, Zhi-Li; Zhao, Hua-Shan; Zhao, Qian; Lei, Xiao-Hua; Ning, Li-Na; Cao, Yu-Jing; Wang, Hai-Bin; Liu, Shuang; Duan, En-Kui

    2016-01-01

    R-spondin proteins are novel Wnt/β-catenin agonists, which signal through their receptors leucine-rich repeat-containing G-protein coupled receptor (LGR) 4/5/6 and substantially enhance Wnt/β-catenin activity. R-spondins are reported to function in embryonic development. They also play important roles in stem cell functions in adult tissues, such as the intestine and mammary glands, which largely rely on Wnt/β-catenin signaling. However, in the skin epithelium and hair follicles, the information about R-spondins is deficient, although the expressions and functions of their receptors, LGR4/5/6, have already been studied in detail. In the present study, highly-enriched expression of the R-spondin family genes (Rspo1/2/3/4) in the hair follicle dermal papilla is revealed. Expression of Rspo1 in the dermal papilla is specifically and prominently upregulated before anagen entry, and exogenous recombinant R-spondin1 protein injection in mid-telogen leads to precocious anagen entry. Moreover, R-spondin1 activates Wnt/β-catenin signaling in cultured bulge stem cells in vitro, changing their fate determination without altering the cell proliferation. Our pioneering study uncovers a role of R-spondin1 in the activation of cultured hair follicle stem cells and the regulation of hair cycle progression, shedding new light on the governance of Wnt/β-catenin signaling in skin biology and providing helpful clues for future treatment of hair follicle disorders. PMID:27104524

  2. Cathepsin L deficiency as molecular defect of furless: hyperproliferation of keratinocytes and pertubation of hair follicle cycling.

    PubMed

    Roth, W; Deussing, J; Botchkarev, V A; Pauly-Evers, M; Saftig, P; Hafner, A; Schmidt, P; Schmahl, W; Scherer, J; Anton-Lamprecht, I; Von Figura, K; Paus, R; Peters, C

    2000-10-01

    Lysosomal cysteine proteinases of the papain family are involved in lysosomal bulk proteolysis, major histocompatibility complex class II mediated antigen presentation, prohormone processing, and extracellular matrix remodeling. Cathepsin L (CTSL) is a ubiquitously expressed major representative of the papain-like family of cysteine proteinases. To investigate CTSL in vivo functions, the gene was inactivated by gene targeting in embryonic stem cells. CTSL-deficient mice develop periodic hair loss and epidermal hyperplasia, acanthosis, and hyperkeratosis. The hair loss is due to alterations of hair follicle morphogenesis and cycling, dilatation of hair follicle canals, and disturbed club hair formation. Hyperproliferation of hair follicle epithelial cells and basal epidermal keratinocytes-both of ectodermal origin-are the primary characteristics underlying the mutant phenotype. Pathological inflammatory responses have been excluded as a putative cause of the skin and hair disorder. The phenotype of CTSL-deficient mice is reminiscent of the spontaneous mouse mutant furless (fs). Analyses of the ctsl gene of fs mice revealed a G149R mutation inactivating the proteinase activity. CTSL is the first lysosomal proteinase shown to be essential for epidermal homeostasis and regular hair follicle morphogenesis and cycling.

  3. Keratin network modifications lead to the mechanical stiffening of the hair follicle fiber.

    PubMed

    Bornschlögl, Thomas; Bildstein, Lucien; Thibaut, Sébastien; Santoprete, Roberto; Fiat, Françoise; Luengo, Gustavo S; Doucet, Jean; Bernard, Bruno A; Baghdadli, Nawel

    2016-05-24

    The complex mechanical properties of biomaterials such as hair, horn, skin, or bone are determined by the architecture of the underlying fibrous bionetworks. Although much is known about the influence of the cytoskeleton on the mechanics of isolated cells, this has been less studied in tridimensional tissues. We used the hair follicle as a model to link changes in the keratin network composition and architecture to the mechanical properties of the nascent hair. We show using atomic force microscopy that the soft keratinocyte matrix at the base of the follicle stiffens by a factor of ∼360, from 30 kPa to 11 MPa along the first millimeter of the follicle. The early mechanical stiffening is concomitant to an increase in diameter of the keratin macrofibrils, their continuous compaction, and increasingly parallel orientation. The related stiffening of the material follows a power law, typical of the mechanics of nonthermal bending-dominated fiber networks. In addition, we used X-ray diffraction to monitor changes in the (supra)molecular organization within the keratin fibers. At later keratinization stages, the inner mechanical properties of the macrofibrils dominate the stiffening due to the progressive setting up of the cystine network. Our findings corroborate existing models on the sequence of biological and structural events during hair keratinization.

  4. Keratin network modifications lead to the mechanical stiffening of the hair follicle fiber

    PubMed Central

    Bornschlögl, Thomas; Bildstein, Lucien; Thibaut, Sébastien; Santoprete, Roberto; Fiat, Françoise; Luengo, Gustavo S.; Doucet, Jean; Bernard, Bruno A.; Baghdadli, Nawel

    2016-01-01

    The complex mechanical properties of biomaterials such as hair, horn, skin, or bone are determined by the architecture of the underlying fibrous bionetworks. Although much is known about the influence of the cytoskeleton on the mechanics of isolated cells, this has been less studied in tridimensional tissues. We used the hair follicle as a model to link changes in the keratin network composition and architecture to the mechanical properties of the nascent hair. We show using atomic force microscopy that the soft keratinocyte matrix at the base of the follicle stiffens by a factor of ∼360, from 30 kPa to 11 MPa along the first millimeter of the follicle. The early mechanical stiffening is concomitant to an increase in diameter of the keratin macrofibrils, their continuous compaction, and increasingly parallel orientation. The related stiffening of the material follows a power law, typical of the mechanics of nonthermal bending-dominated fiber networks. In addition, we used X-ray diffraction to monitor changes in the (supra)molecular organization within the keratin fibers. At later keratinization stages, the inner mechanical properties of the macrofibrils dominate the stiffening due to the progressive setting up of the cystine network. Our findings corroborate existing models on the sequence of biological and structural events during hair keratinization. PMID:27162354

  5. Hair follicles stimulation effects of gelatin nanofibers containing silver nanoparticles.

    PubMed

    Tura, V; Hagiu, B A; Mangalagiu, I I

    2010-04-01

    In the present work we studied gelatin nanofibers containing silver nanoparticles of 14 +/- 6 nm mean diameter, prepared by electrospinning. The electrospinnable solution was obtained by drop-wise adding a AgNO3/acetic acid solution to gelatin which had previously been dissolved in a mixture of formic acid and acetic acid. The silver metallic nanoparticles were formed due to the reducing action of the formic acid. The resulted material was characterized by transmission electron microscopy (TEM), scanning electron microscopy (SEM), attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) and X-ray diffraction (XRD). Subcutaneous implants in rabbits demonstrated that the gelatin nanofibers containing silver nanoparticles were resorbed with no inflammatory reactions. An increased number of secondary hair follicles developed in tissue regions close to implants, suggesting the existence of a stimulation effect of silver nanoparticles on hair follicles.

  6. Msi2 Maintains Quiescent State of Hair Follicle Stem Cells by Directly Repressing the Hh Signaling Pathway.

    PubMed

    Ma, Xianghui; Tian, Yuhua; Song, Yongli; Shi, Jianyun; Xu, Jiuzhi; Xiong, Kai; Li, Jia; Xu, Wenjie; Zhao, Yiqiang; Shuai, Jianwei; Chen, Lei; Plikus, Maksim V; Lengner, Christopher J; Ren, Fazheng; Xue, Lixiang; Yu, Zhengquan

    2017-01-29

    Hair follicles (HFs) undergo precisely regulated cycles of active regeneration (anagen), involution (catagen), and relative quiescence (telogen). Hair follicle stem cells (HFSCs) play important roles in regenerative cycling. Elucidating mechanisms that govern HFSC behavior can help uncover the underlying principles of hair development, hair growth disorders, and skin cancers. RNA-binding proteins of the Musashi (Msi) have been implicated in the biology of different stem cell types, yet they have not been studied in HFSCs. Here we utilized gain- and loss-of-function mouse models to demonstrate that forced MSI2 expression retards anagen entry and consequently delays hair growth, whereas loss of Msi2 enhances hair regrowth. Furthermore, our findings show that Msi2 maintains quiescent state of HFSCs in the process of the telogen-to-anagen transition. At the molecular level, our unbiased transcriptome profiling shows that Msi2 represses Hedgehog signaling activity and that Shh is its direct target in the hair follicle. Taken together, our findings reveal the importance of Msi2 in suppressing hair regeneration and maintaining HFSC quiescence. The previously unreported Msi2-Shh-Gli1 pathway adds to the growing understanding of the complex network governing cyclic hair growth.

  7. Therapeutic strategy for hair regeneration: Hair cycle activation, niche environment modulation, wound-induced follicle neogenesis and stem cell engineering

    PubMed Central

    Chueh, Shan-Chang; Lin, Sung-Jan; Chen, Chih-Chiang; Lei, Mingxing; Wang, Ling Mei; Widelitz, Randall B.; Hughes, Michael W.; Jiang, Ting-Xing; Chuong, Cheng Ming

    2013-01-01

    Introduction There are major new advancements in the fields of stem cell biology, developmental biology, regenerative hair cycling, and tissue engineering. The time is ripe to integrate, translate and apply these findings to tissue engineering and regenerative medicine. Readers will learn about new progress in cellular and molecular aspects of hair follicle development, regeneration and potential therapeutic opportunities these advances may offer. Areas covered Here we use hair follicle formation to illustrate this progress and to identify targets for potential strategies in therapeutics. Hair regeneration is discussed in four different categories. (1) Intra-follicle regeneration (or renewal) is the basic production of hair fibers from hair stem cells and dermal papillae in existing follicles. (2) Chimeric follicles via epithelial-mesenchymal recombination to identify stem cells and signaling centers. (3) Extra-follicular factors including local dermal and systemic factors can modulate the regenerative behavior of hair follicles, and may be relatively easy therapeutic targets. (4) Follicular neogenesis means the de novo formation of new follicles. In addition, scientists are working to engineer hair follicles, which require hair forming competent epidermal cells and hair inducing dermal cells. Expert opinion Ideally self-organizing processes similar to those occurring during embryonic development should be elicited with some help from biomaterials. PMID:23289545

  8. Targeting to the hair follicles: current status and potential.

    PubMed

    Wosicka, Hanna; Cal, Krzysztof

    2010-02-01

    The pilosebaceous unit is a complex structure that undergoes a specific growth cycle and comprises a few important drug targeting sites. For example, drugs can be targeted to the bulge region with stem cells or to the sebaceous glands. Interest in pilosebaceous units is directed towards their utilization as reservoirs for localized therapy and also as a transport pathway for systemic drug delivery. Improved investigative methods, such as differential stripping, are being developed in order to determine follicular penetration. This article reviews relevant aspects of effective follicle-targeting formulations and delivery systems as well as the activity status of hair follicles, and variations in follicle size and distribution throughout various body regions. Each of these factors strongly affects follicular permeation. We provide examples of improved penetration of particle-based formulations and of a size-dependent manner of follicular penetration. Contradictions are also discussed, indicating the need for detailed future investigations.

  9. Skin, Hair, and Nails

    MedlinePlus

    ... and water, helps regulate body temperature through perspiration (sweating), and protects from the sun's damaging ultraviolet rays. ... skin contains thousands of cells and hundreds of sweat glands, oil glands, nerve endings, and blood vessels. ...

  10. Hair follicle signaling networks: a dermal papilla-centric approach.

    PubMed

    Ramos, Raul; Guerrero-Juarez, Christian F; Plikus, Maksim V

    2013-10-01

    Functional testing of dermal papilla (DP) signaling inputs into hair follicle (HF) morphogenesis and regeneration is becoming possible with the advent of new Cre lines. Targeted deletion of the signature genes in early DP precursors has revealed significant signaling redundancy during HF morphogenesis. Furthermore, the DP lineage commitment program can be exploited for generating highly inductive DP cells to be used in HF bioengineering assays.

  11. The angiogenic properties of the rat vibrissa hair follicle associate with the bulb.

    PubMed

    Stenn, K S; Fernandez, L A; Tirrell, S J

    1988-03-01

    As the hair follicle is one of the most rapidly growing tissues in the body, it must be nourished by a rich blood supply. Histological studies have indicated that the number of vessels about a growing follicle exceeds that about a resting follicle, so we postulated that the hair follicle might provide its own angiogenic stimulus during certain phases of its growth. Reported here are experiments testing the angiogenic properties of the growing (anagen) hair follicle. Using the rabbit corneal pocket angiogenesis assay and cycled anagen rat vibrissae hair follicles, we found that the mesenchymal dermal papilla had no angiogenic properties, but the anagen bulb was angiogenic. These findings suggest a mechanism for the cycling of hair follicles and an example of normal epithelium to mesenchyme interactions.

  12. Beta-catenin can induce hair follicle stem cell differentiation into transit-amplifying cells through c-myc activation.

    PubMed

    Shen, Qiong; Yu, Weirong; Fang, Yong; Yao, Min; Yang, Penggao

    2017-02-01

    Hair follicle stem cells play important roles in maintaining homeostasis and skin tissue self-renewal. Transit-amplifying cells represent the transition of cells from hair follicle stem cells into differentiated epidermal cells. Thus far, the signaling pathway and the molecular biological mechanism that regulate the proliferation and differentiation of hair follicle stem cells remain unclear. In this paper, we studied the relationship between β-catenin and c-myc during the process of the differentiation of hair follicle stem cells into transit-amplifying cells. Based on our results, the expression of β-catenin can activate the nuclear gene c-myc and regulate the expression of transit-amplifying cell markers K15, K19, a6-integrin and β1-integrin, indicating that β-catenin is involved in the transformation process from hair follicle stem cells to transit-amplifying cells and suggesting that β-catenin plays an important biological role in the induction of this differentiation process.

  13. Lack of the vitamin D receptor is associated with reduced epidermal differentiation and hair follicle growth.

    PubMed

    Xie, Zhongjion; Komuves, László; Yu, Qian-Chun; Elalieh, Hashem; Ng, Dean C; Leary, Colin; Chang, Sandra; Crumrine, Debra; Yoshizawa, Tatsuya; Kato, Shigeaki; Bikle, Daniel D

    2002-01-01

    The active vitamin D metabolite, 1,25-dihydroxyvitamin D, acting through the vitamin D receptor, regulates the expression of genes in a variety of vitamin D-responsive tissues, including the epidermis. To investigate the role of the vitamin D receptor in mediating epidermal differentiation, we examined the histomorphology and expression of differentiation markers in the epidermis of vitamin D receptor knockout mice generated by gene targeting. The homozygous knockout mouse displayed a phenotype that closely resembles vitamin D-dependent rickets type II in humans, including the development of rickets and alopecia. Hair loss developed by 3 mo after birth and gradually led to nearly total hair loss by 8 mo. Histologic analysis of the skin of homozygous knockout mice revealed dilation of the hair follicles with the formation of dermal cysts starting at the age of 3 wk. These cysts increased in size and number with age. Epidermal differentiation markers, including involucrin, profilaggrin, and loricrin, detected by immunostaining and in situ hybridization, showed decreased expression levels in homozygous knockout mice from birth until 3 wk, preceding the morphologic changes observed in the hair follicles. Keratin 10 levels, however, were not reduced. At the ultrastructural level, homozygous knockout mice showed increased numbers of small dense granules in the granular layer with few or no surrounding keratin bundles and a loss of keratohyalin granules. Thus, both the interfollicular epidermis and the hair follicle appear to require the vitamin D receptor for normal differentiation. The temporal abnormalities between the two processes reflect the apparent lack of requirement for the vitamin D receptor during the anagen phase of the first (developmental) hair cycle, but with earlier effects on the terminal differentiation of the interfollicular epidermis.

  14. At the dawn of hair research - testing the limits of hair follicle regeneration.

    PubMed

    Plikus, Maksim V

    2014-05-01

    In the late 1960s, tissue recombination studies by Roy Oliver on the model of rat vibrissae provided invaluable information about the morphogenetic properties of hair follicles. Now more than ever, the field is hopeful that a clinically reproducible procedure for cell-based hair regeneration is achievable. Highly inductive mesenchymal cells are thought to be the key ingredient necessary to achieve robust hair regeneration, and efforts are underway to develop protocols to improve the naturally low inductive properties of human dermal papilla cells. In this respect, the original studies by Oliver provide essential rodent research benchmarks, which current-day human studies should aim to reach.

  15. Red ginseng extract promotes the hair growth in cultured human hair follicles.

    PubMed

    Park, Gyeong-Hun; Park, Ki-young; Cho, Hong-il; Lee, Sang-Min; Han, Ji Su; Won, Chong Hyun; Chang, Sung Eun; Lee, Mi Woo; Choi, Jee Ho; Moon, Kee Chan; Shin, Hyoseung; Kang, Yong Jung; Lee, Dong Hun

    2015-03-01

    Ginseng has been shown to promote hair growth in several recent studies. However, its effects on human hair follicles and its mechanisms of action have not been sufficiently elucidated. This study aimed to investigate the hair growth-promoting effects of red ginseng extract (RGE) and its ginsenosides. The proliferative activities of cultured human hair follicles treated with RGE and ginsenoside-Rb1 were assessed using Ki-67 immunostaining. Their effects on isolated human dermal papilla cells (hDPCs) were evaluated using cytotoxicity assays, immunoblot analysis of signaling proteins, and the determination of associated growth factors. We examined the ability of RGE and ginsenosides to protect hair matrix keratinocyte proliferation against dihydrotestosterone (DHT)-induced suppression and their effects on the expression of androgen receptor. The in vivo hair growth-promoting effect of RGE was also investigated in C57BL/6 mice. Both RGE and ginsenoside-Rb1 enhanced the proliferation of hair matrix keratinocytes. hDPCs treated with RGE or ginsenoside-Rb1 exhibited substantial cell proliferation and the associated phosphorylation of ERK and AKT. Moreover, RGE, ginsenoside-Rb1, and ginsenoside-Rg3 abrogated the DHT-induced suppression of hair matrix keratinocyte proliferation and the DHT-induced upregulation of the mRNA expression of androgen receptor in hDPCs. Murine experiments revealed that the subcutaneous injection of 3% RGE resulted in more rapid hair growth than the negative control. In conclusion, RGE and its ginsenosides may enhance hDPC proliferation, activate ERK and AKT signaling pathways in hDPCs, upregulate hair matrix keratinocyte proliferation, and inhibit the DHT-induced androgen receptor transcription. These results suggest that red ginseng may promote hair growth in humans.

  16. Red Ginseng Extract Promotes the Hair Growth in Cultured Human Hair Follicles

    PubMed Central

    Park, Gyeong-Hun; Park, Ki-young; Cho, Hong-il; Lee, Sang-Min; Han, Ji Su; Chang, Sung Eun; Lee, Mi Woo; Choi, Jee Ho; Moon, Kee Chan; Shin, Hyoseung; Kang, Yong Jung; Lee, Dong Hun

    2015-01-01

    Abstract Ginseng has been shown to promote hair growth in several recent studies. However, its effects on human hair follicles and its mechanisms of action have not been sufficiently elucidated. This study aimed to investigate the hair growth-promoting effects of red ginseng extract (RGE) and its ginsenosides. The proliferative activities of cultured human hair follicles treated with RGE and ginsenoside-Rb1 were assessed using Ki-67 immunostaining. Their effects on isolated human dermal papilla cells (hDPCs) were evaluated using cytotoxicity assays, immunoblot analysis of signaling proteins, and the determination of associated growth factors. We examined the ability of RGE and ginsenosides to protect hair matrix keratinocyte proliferation against dihydrotestosterone (DHT)-induced suppression and their effects on the expression of androgen receptor. The in vivo hair growth-promoting effect of RGE was also investigated in C57BL/6 mice. Both RGE and ginsenoside-Rb1 enhanced the proliferation of hair matrix keratinocytes. hDPCs treated with RGE or ginsenoside-Rb1 exhibited substantial cell proliferation and the associated phosphorylation of ERK and AKT. Moreover, RGE, ginsenoside-Rb1, and ginsenoside-Rg3 abrogated the DHT-induced suppression of hair matrix keratinocyte proliferation and the DHT-induced upregulation of the mRNA expression of androgen receptor in hDPCs. Murine experiments revealed that the subcutaneous injection of 3% RGE resulted in more rapid hair growth than the negative control. In conclusion, RGE and its ginsenosides may enhance hDPC proliferation, activate ERK and AKT signaling pathways in hDPCs, upregulate hair matrix keratinocyte proliferation, and inhibit the DHT-induced androgen receptor transcription. These results suggest that red ginseng may promote hair growth in humans. PMID:25396716

  17. Chitosan nanoparticles for targeting and sustaining minoxidil sulphate delivery to hair follicles.

    PubMed

    Matos, Breno Noronha; Reis, Thaiene Avila; Gratieri, Taís; Gelfuso, Guilherme Martins

    2015-04-01

    This work developed minoxidil sulphate-loaded chitosan nanoparticles (MXS-NP) for targeted delivery to hair follicles, which could sustain drug release and improve the topical treatment of alopecia. Chitosan nanoparticles were obtained using low-molecular weight chitosan and tripolyphosphate as crosslink agent. MXS-NP presented a monomodal distribution with hydrodynamic diameter of 235.5 ± 99.9 nm (PDI of 0.31 ± 0.01) and positive zeta potential (+38.6 ± 6.0 mV). SEM analysis confirmed nanoparticles average size and spherical shape. A drug loading efficiency of 73.0 ± 0.3% was obtained with polymer:drug ratio of 1:1 (w/w). Drug release through cellulose acetate membranes from MXS-NP was sustained in about 5 times in comparison to the diffusion rate of MXS from the solution (188.9 ± 6.0 μg/cm(2)/h and 35.4 ± 1.8 μg/cm(2)/h). Drug permeation studies through the skin in vitro, followed by selective recovery of MXS from the hair follicles, showed that MXS-NP application resulted in a two-fold MXS increase into hair follicles after 6h in comparison to the control solution (5.9 ± 0.6 μg/cm(2) and 2.9 ± 0.8 μg/cm(2)). MXS-loading in nanoparticles appears as a promising and easy strategy to target and sustain drug delivery to hair follicles, which may improve the topical treatment of alopecia.

  18. The correlation of TRPM1 (Melastatin) mRNA expression with microphthalmia-associated transcription factor (MITF) and other melanogenesis-related proteins in normal and pathological skin, hair follicles and melanocytic nevi

    PubMed Central

    Lu, Song; Slominski, Andrzej; Yang, Sung-Eun; Sheehan, Christine; Ross, Jeffrey; Carlson, J. Andrew

    2010-01-01

    Background Melastatin (TRPM1), a.k.a. transient receptor potential cation channel, subfamily M, member 1 (TRPM-1) regulates melanocyte differentiation and proliferation. TRPM1 is transcriptionally regulated by the essential melanocyte transcription factor MITF (microphthalmia-associated transcription factor). For the most part, MITF expression is preserved during melanoma progression, while TRPM1 mRNA expression decreases or is completely lost. The loss of TRPM1 is associated with melanomas that are more aggressive. Objective To assess the relationship between TRPM1 mRNA expression and the expression of MITF and nine other markers of melanocytes and melanin-related proteins by immunohistochemistry in normal skin, scars, hair follicles and ordinary melanocytic nevi. Methods Samples of normal skin (n = 102; from tumor excisions and plastic procedures), scars (n = 5; from re-excision specimens) and compound melanocytic nevi (n = 4) were evaluated for the presence of TRPM1 mRNA transcripts as detected by chromogenic in situ hybridization (CISH). Immunohistochemical techniques were used to detect melanin-related proteins including: MITF, S100 protein, Mart-1, tyrosinase, Mel5, HMB45, tyrosinase-related protein-1 (TRP1), TRP2 and α-melanocyte stimulating hormone (αMSH). The labeling index (LI) was defined as the number of intraepidermal cells expressing mRNA or protein per one hundred basal keratinocytes. Results A wide range of LI was found for all markers (0–33 positive cells/100 keratinocytes). When these LI were compared, no significant differences in the expression of MITF, S100, Mart1, tyrosinase proteins and TRPM1 mRNA were identified. The LI for TRPM1 mRNA expression ranged from 74% of that for MITF to 86% for tyrosinase. The LI for TRP-1, TRP-2 and Mel5 was similar to that of TRPM1, while HMB-45 had a significantly lower LI than all other markers. TRPM1 mRNA correlated most tightly with MITF and tyrosinase expression (r = 0.81 and 0.68, respectively, both p

  19. Delivery and targeting of nanoparticles into hair follicles.

    PubMed

    Fang, Chia-Lang; Aljuffali, Ibrahim A; Li, Yi-Ching; Fang, Jia-You

    2014-01-01

    It has been demonstrated that nanoparticles used for follicular delivery provide some advantages over conventional pathways, including improved skin bioavailability, enhanced penetration depth, prolonged residence duration, fast transport into the skin and tissue targeting. This review describes recent developments using nanotechnology approaches for drug delivery into the follicles. Different types of nanosystems may be employed for management of follicular permeation, such as polymeric nanoparticles, metallic nanocrystals, liposomes, and lipid nanoparticles. This review systematically introduces the mechanisms of follicles for nanoparticulate penetration, highlighting the therapeutic potential of drug-loaded nanoparticles for treating skin diseases. Special attention is paid to the use of nanoparticles in treating appendage-related disorders, in particular, nanomedical strategies for treating alopecia, acne, and transcutaneous immunization.

  20. Influence of the hair cycle on the thickness of mouse skin

    SciTech Connect

    Hansen, L.S.; Coggle, J.E.; Wells, J.; Charles, M.W.

    1984-12-01

    The data on mouse skin thickness reported here was prompted by the need to know the true position of basal cells of the epidermis and hair follicles as these are important cells at risk for a variety of skin reactions including carcinogenesis following exposure to radiation. There is little reliable data in the literature and most previous reports have ignored the shrinkage of skin that occurs because of its natural elasticity. The values determined for mouse flank skin in telogen--the resting phase of the hair cycle for the different skin layers--are epidermis 10 micron, corium 250 micron, adipose layer 150 micron, and hair follicle depth 150 micron. Three days after chemical depilation which triggers the hair follicles into active cycle (anagen) the epidermis doubles in thickness, remains at this value for 7 days, and then gradually returns to telogen values by day 18. The corium and adipose layers also increase significantly to reach approximately 390 micron and approximately 260 micron, respectively, by day 10 and then return to control values from day 15 onward. The change in hair follicles depths are more dramatic with active follicle basal cells reaching approximately 450-550 micron into the adipose layer between days 7 and 15. One important finding is that chemical depilation does not affect the telogen thickness of skin-the teleogen values for the epidermis and dermis immediately prior to and immediately after depilation were similar to those 23 days later at the beginning of the next telogen phase.

  1. Differentiating the stem cell pool of human hair follicle outer root sheath into functional melanocytes.

    PubMed

    Schneider, Marie; Dieckmann, Christina; Rabe, Katrin; Simon, Jan-Christoph; Savkovic, Vuk

    2014-01-01

    Bench-to-Bedside concepts for regenerative therapy place significant weight on noninvasive approaches, with harvesting of the starting material as a header. This is particularly important in autologous treatments, which use one's bodily constituents for therapy. Precisely the stretch between obtaining therapeutic elements invasively and noninvasively places non-intrusive "sampling" rather than "biopsy" in the center of the road map of developing an autologous regenerative therapy. We focus on such a noninvasively available source of adult stem cells that we carry with us throughout our life, available at our fingertips-or shall we say hair roots, by a simple plucking of hair: the human hair follicle. This chapter describes an explant procedure for cultivating melanocytes differentiated from the stem cell pool of the hair follicle Outer Root Sheath (ORS). In vivo, the most abundant derivatives of the heterogeneous ORS stem cell pool are epidermal cells-melanocytes and keratinocytes which complete their differentiation-either spontaneously or upon picking up regenerative cues from damaged skin-and migrate from the ORS towards the adjacent regenerating area of the epidermis. We have taken advantage of the ORS developmental potential by optimizing explant primary culture, expansion and melanogenic differentiation of resident ORS stem cells towards end-stage melanocytes in order to obtain functional melanocytes noninvasively for the purposes of transplantation and use them for the treatment of depigmentation disorders. Our protocol specifies sampling of hair with their ORS, follicle medium-air interface primary culture, stimulation of cell outgrowth, adherent culture and differentiation of ORS stem cells and precursors towards fully functional melanocytes. Along with cultivation, we describe selection techniques for establishing and maintaining a pure melanocyte population and methods suitable for determining melanocyte identity.

  2. Mutations in TSPEAR, Encoding a Regulator of Notch Signaling, Affect Tooth and Hair Follicle Morphogenesis

    PubMed Central

    Samuelov, Liat; Bertolini, Marta; Weissglas-Volkov, Daphna; Eskin-Schwartz, Marina; Malchin, Natalia; Bochner, Ron; Fainberg, Gilad; Goldberg, Ilan; Sugawara, Koji; Tsuruta, Daisuke; Morasso, Maria; Shalev, Stavit; Gallo, Richard L.; Shomron, Noam; Paus, Ralf; Sprecher, Eli

    2016-01-01

    Despite recent advances in our understanding of the pathogenesis of ectodermal dysplasias (EDs), the molecular basis of many of these disorders remains unknown. In the present study, we aimed at elucidating the genetic basis of a new form of ED featuring facial dysmorphism, scalp hypotrichosis and hypodontia. Using whole exome sequencing, we identified 2 frameshift and 2 missense mutations in TSPEAR segregating with the disease phenotype in 3 families. TSPEAR encodes the thrombospondin-type laminin G domain and EAR repeats (TSPEAR) protein, whose function is poorly understood. TSPEAR knock-down resulted in altered expression of genes known to be regulated by NOTCH and to be involved in murine hair and tooth development. Pathway analysis confirmed that down-regulation of TSPEAR in keratinocytes is likely to affect Notch signaling. Accordingly, using a luciferase-based reporter assay, we showed that TSPEAR knock-down is associated with decreased Notch signaling. In addition, NOTCH1 protein expression was reduced in patient scalp skin. Moreover, TSPEAR silencing in mouse hair follicle organ cultures was found to induce apoptosis in follicular epithelial cells, resulting in decreased hair bulb diameter. Collectively, these observations indicate that TSPEAR plays a critical, previously unrecognized role in human tooth and hair follicle morphogenesis through regulation of the Notch signaling pathway. PMID:27736875

  3. Toluene Diisocyanate (TDI) Disposition and Co-Localization of Immune Cells in Hair Follicles

    PubMed Central

    Nayak, Ajay P.; Hettick, Justin M.; Siegel, Paul D.; Anderson, Stacey E.; Long, Carrie M.; Green, Brett J.; Beezhold, Donald H.

    2014-01-01

    Diisocyanates (dNCOs) are potent chemical allergens utilized in various industries. It has been proposed that skin exposure to dNCOs produces immune sensitization leading to work-related asthma and allergic disease. We examined dNCOs sensitization by using a dermal murine model of toluene diisocyanate (TDI) exposure to characterize the disposition of TDI in the skin, identify the predominant haptenated proteins, and discern the associated antigen uptake by dendritic cells. Ears of BALB/c mice were dosed once with TDI (0.1% or 4% v/v acetone). Ears and draining lymph nodes (DLNs) were excised at selected time points between 1 h and 15 days post-exposure and were processed for histological, immunohistochemical, and proteomic analyses. Monoclonal antibodies specific for TDI-haptenated protein (TDI-hp) and antibodies to various cell markers were utilized with confocal microscopy to determine co-localization patterns. Histopathological changes were observed following exposure in ear tissue of mice dosed with 4% TDI/acetone. Immunohistochemical staining demonstrated TDI-hp localization in the stratum corneum, hair follicles, and sebaceous glands. TDI-hp were co-localized with CD11b+ (integrin αM/Mac-1), CD207+ (langerin), and CD103+ (integrin αE) cells in the hair follicles and in sebaceous glands. TDI-hp were also identified in the DLN 1 h post-exposure. Cytoskeletal and cuticular keratins along with mouse serum albumin were identified as major haptenated species in the skin. The results of this study demonstrate that the stratum corneum, hair follicles, and associated sebaceous glands in mice are dendritic cell accessible reservoirs for TDI-hp and thus identify a mechanism for immune recognition following epicutaneous exposure to TDI. PMID:24798378

  4. Distributions of sulphur and other elements in human hair follicles

    NASA Astrophysics Data System (ADS)

    Ollerhead, R. W.; Legge, G. J. F.; Jones, L. N.

    1989-04-01

    Distributions of sulphur and other elements have been measured in several different specimens of human hair follicles. Whole specimens, longitudinal bisections, and 10 μm thick longitudinal sections have been analyzed by PIXE using the Melbourne scanning proton microprobe. Elemental maps consistently showed that sulphur contents of the presumptive hair shaft (PHS) were uniformly low from 0 to 400 μm (bulb end), increased continuously from about 400 to 800 μm, and reached a plateau. Sulphur levels were uniformly low in the inner root sheath. These observations are consistent with previous protein analysis of PHS sections, indicating sequential synthesis of the major classes of keratin proteins. Maps of other elements indicated that Si, Ca, and Fe tended to be concentrated randomly, whereas, P, Cl, K, and Zn were more uniformly distributed. Average relative concentrations of Si, P, Cl, K, Ca, Fe, Cu, and Zn were estimated from total X-ray spectra.

  5. Advanced chemical imaging and comparison of human and porcine hair follicles for drug delivery by confocal Raman microscopy

    NASA Astrophysics Data System (ADS)

    Franzen, Lutz; Mathes, Christiane; Hansen, Steffi; Windbergs, Maike

    2013-06-01

    Hair follicles have recently gained a lot of interest for dermal drug delivery. They provide facilitated penetration into the skin and a high potential to serve as a drug depot. In this area of research, excised pig ear is a widely accepted in vitro model to evaluate penetration of drug delivery into hair follicles. However, a comparison of human and porcine follicles in terms of chemical composition has not been performed so far. In this study, we applied confocal Raman microscopy as a chemically selective imaging technique to compare human and porcine follicle composition and to visualize component distribution within follicle cross-sections. Based on the evaluation of human and porcine Raman spectra optical similarity for both species was successfully confirmed. Furthermore, cyanoacrylate skin surface biopsies, which are generally used to determine the extent of follicular penetration, were imaged by a novel complementary analytical approach combining confocal Raman microscopy and optical profilometry. This all-encompassing analysis allows investigation of intactness and component distribution of the excised hair bulb in three dimensions. Confocal Raman microscopy shows a high potential as a noninvasive and chemically selective technique for the analysis of trans-follicular drug delivery.

  6. Strategies to enhance epithelial-mesenchymal interactions for human hair follicle bioengineering.

    PubMed

    Ohyama, Manabu; Veraitch, Ophelia

    2013-05-01

    Hair follicle morphogenesis and regeneration depend on intensive but well-orchestrated interactions between epithelial and mesenchymal components. Accordingly, the enhancement of this crosstalk represents a promising approach to achieve successful bioengineering of human hair follicles. The present article summarizes the techniques, both currently available and potentially feasible, to promote epithelial-mesenchymal interactions (EMIs) necessary for human hair follicle regeneration. The strategies include the preparation of epithelial components with high receptivity to trichogenic dermal signals and/or mesenchymal cell populations with potent hair inductive capacity. In this regard, bulge epithelial stem cells, keratinocytes predisposed to hair follicle fate or keratinocyte precursor cells with plasticity may provide favorable epithelial cell populations. Dermal papilla cells sustaining intrinsic hair inductive capacity, putative dermal papilla precursor cells in the dermal sheath/neonatal dermis or trichogenic dermal cells derived from undifferentiated stem/progenitor cells are promising candidates as hair inductive dermal cells. The most established protocol for in vivo hair follicle reconstitution is co-grafting of epithelial and mesenchymal components into immunodeficient mice. In theory, combination of individually optimized cellular components of respective lineages should elicit most intensive EMIs to form hair follicles. Still, EMIs can be further ameliorated by the modulation of non-cell autonomous conditions, including cell compartmentalization to replicate the positional relationship in vivo and humanization of host environment by preparing human stromal bed. These approaches may not always synergistically intensify EMIs, however, step-by-step investigation probing optimal combinations should maximally enhance EMIs to achieve successful human hair follicle bioengineering.

  7. Foxi3 deficiency compromises hair follicle stem cell specification and activation

    PubMed Central

    Shirokova, Vera; Biggs, Leah C.; Jussila, Maria; Ohyama, Takahiro; Groves, Andrew K.; Mikkola, Marja L.

    2017-01-01

    The hair follicle is an ideal system to study stem cell specification and homeostasis due to its well characterized morphogenesis and stereotypic cycles of stem cell activation upon each hair cycle to produce a new hair shaft. The adult hair follicle stem cell niche consists of two distinct populations, the bulge and the more activation-prone secondary hair germ. Hair follicle stem cells are set aside during early stages of morphogenesis. This process is known to depend on the Sox9 transcription factor, but otherwise the establishment of the hair follicle stem cell niche is poorly understood. Here we show that that mutation of Foxi3, a Forkhead family transcription factor mutated in several hairless dog breeds, compromises stem cell specification. Further, loss of Foxi3 impedes hair follicle downgrowth and progression of the hair cycle. Genome-wide profiling revealed a number of downstream effectors of Foxi3 including transcription factors with a recognized function in hair follicle stem cells such as Lhx2, Runx1, and Nfatc1, suggesting that the Foxi3 mutant phenotype results from simultaneous downregulation of several stem cell signature genes. We show that Foxi3 displays a highly dynamic expression pattern during hair morphogenesis and cycling, and identify Foxi3 as a novel secondary hair germ marker. Absence of Foxi3 results in poor hair regeneration upon hair plucking, and a sparse fur phenotype in unperturbed mice that exacerbates with age, caused by impaired secondary hair germ activation leading to progressive depletion of stem cells. Thus, Foxi3 regulates multiple aspects of hair follicle development and homeostasis. PMID:26992132

  8. Mutant laboratory mice with abnormalities in hair follicle morphogenesis, cycling, and/or structure: an update.

    PubMed

    Nakamura, Motonobu; Schneider, Marlon R; Schmidt-Ullrich, Ruth; Paus, Ralf

    2013-01-01

    Human hair disorders comprise a number of different types of alopecia, atrichia, hypotrichosis, distinct hair shaft disorders as well as hirsutism and hypertrichosis. Their causes vary from genodermatoses (e.g. hypotrichoses) via immunological disorders (e.g. alopecia areata, autoimmune cicatrical alopecias) to hormone-dependent abnormalities (e.g. androgenetic alopecia). A large number of spontaneous mouse mutants and genetically engineered mice develop abnormalities in hair follicle morphogenesis, cycling, and/or hair shaft formation, whose analysis has proven invaluable to define the molecular regulation of hair growth, ranging from hair follicle development, and cycling to hair shaft formation and stem cell biology. Also, the accumulating reports on hair phenotypes of mouse strains provide important pointers to better understand the molecular mechanisms underlying human hair growth disorders. Since numerous new mouse mutants with a hair phenotype have been reported since the publication of our earlier review on this matter a decade ago, we present here an updated, tabulated mini-review. The updated annotated tables list a wide selection of mouse mutants with hair growth abnormalities, classified into four categories: Mutations that affect hair follicle (1) morphogenesis, (2) cycling, (3) structure, and (4) mutations that induce extrafollicular events (for example immune system defects) resulting in secondary hair growth abnormalities. This synthesis is intended to provide a useful source of reference when studying the molecular controls of hair follicle growth and differentiation, and whenever the hair phenotypes of a newly generated mouse mutant need to be compared with existing ones.

  9. In vivo alteration of the keratin 17 gene in hair follicles by oligonucleotide-directed gene targeting.

    PubMed

    Fan, W; Yoon, K

    2003-12-01

    Using intradermal injection of a chimeric RNA-DNA oligonucleotide (RDO) or a single-stranded oligonucleotide (ssODN) into murine skin, we attempted to make a dominant mutation (R94p) in the conserve alpha-helical domain of keratin 17 (K17), the same mutation found in pachyononychia congenichia type 2 (PC-2) patients with phenotypes ranging from twisted hair and multiple pilosebaceous cysts. Both K17A-RDO and -ssODN contained a single base mismatch (CGC to CCC) to alter the normal K17 sequence to cause an amino acid substitution (R94P). The complexes consisting of oligonucleotides and cationic liposomes were injected to C57B1/6 murine skin at 2 and 5 day after birth. Histological examination of skin biopsies at postnatal day 8 from several mice showed consistent twisted hair shafts or broken hair follicles at the sebaceous gland level and occasional rupture of the hair bulb or epidermal cyst-like changes. In the injected area, the number of full anagen hair follicles decrease by 50%. Injection of the control oligonucleotide, identical to K17A-RDO but containing no mismatch to the normal sequence, did not result in any detectable abnormality. The frequency of gene alteration was lower than 3%, according to the restriction fragment length polymorphism (RFLP) analysis of the genomic DNA isolated by dissection of hair follicles from slides. Although intradermal injection of K17A-RDO or K17-ssODN caused a dominant mutation in K17 affecting hair growth and morphology, these phenotypic changes were transient either due to the compensation of K17 by other keratins or the replacement of the mutated cells by normal surrounding cells during hair growth.

  10. Synthesis and Validation of Functional Nanogels as pH-Sensors in the Hair Follicle.

    PubMed

    Dimde, Mathias; Sahle, Fitsum Feleke; Wycisk, Virginia; Steinhilber, Dirk; Camacho, Luis Cuellar; Licha, Kai; Lademann, Jürgen; Haag, Rainer

    2017-04-10

    In the present study, a pH responsive dendritic polyglycerol nanogel (dPG-NG) is developed to measure the pH values inside the hair follicle (HF) using an ex vivo porcine ear model. The macromolecular precursors are labeled with a pH sensitive indodicarbocyanine dye (pH-IDCC) and a control dye (indocarbocyanine dye: ICC) and crosslinked via a mild and surfactant-free Thiol-Michael reaction using an inverse nanoprecipitation method. With this method, it is possible to prepare tailor-made particles in the range of 100 nm to 1 µm with a narrow polydispersity. The dPG-NGs are characterized using dynamic light scattering, nanoparticle tracking analysis, and atomic force microscopy. Systematic analysis of confocal microscope images of histological sections of the skin enables accurate determination of the pH gradient inside the HF. The results show that these novel pH-nanosensors deeply penetrate the skin via the follicular pathway and the pH of the pig hair follicles increase from 6.5 at the surface of the skin to 7.4 in deeper areas of the HF. The pH-nanosensor shows no toxicity potentials.

  11. Three different clinical faces of the same histopathological entity: hair follicle nevus, trichofolliculoma and accessory tragus*

    PubMed Central

    Karabulut, Yasemin Yuyucu; Şenel, Engin; Karabulut, Hacı Halil; Dölek, Yasemin

    2015-01-01

    BACKGROUND Hair follicle nevus is a rare, congenital hamartoma with follicular differentiation characterized histologically by numerous, tiny, mature hair follicles. Trichofolliculoma, the histopathological features of which are quite similar to those of hair follicle nevus, is also a hamartoma that differs from hair follicle. Accessory tragus is a relatively common, benign congenital abnormality of the external ear with an incidence rate of 1 to 10 per 1,000 live births. OBJECTIVE This study seeks to assess the discriminatory value of currently available, histological criteria in the differential diagnosis of hair follicle nevus, accessory tragi and trichofolliculoma. METHODS Twenty-one patients comprising 9 cases of hair follicle nevus, 8 accessory tragi patients and 4 trichofolliculoma cases, were recruited to perform the study. RESULTS There were 10 males and 11 females in the study group. No significant difference was observed between the three study groups in terms of age, gender or histopathological parameters such as density of hair follicles, subcutaneous fat score and presence of connective tissue framework. Cartilaginous component was seen in 8 cases that were diagnosed as accessory tragi, while central cyst and radiating hair follicles were seen in 4 cases which were diagnosed as trichofolliculoma. CONCLUSION The results of our study showed that diagnostic discrimination of these diseases could be made only with the clinicopathologic correlation because of their clinical and histopathological similarities. PMID:26375221

  12. Hair follicle nevi and accessory tragi: variable quantity of adipose tissue in connective tissue framework.

    PubMed

    Ban, M; Kamiya, H; Yamada, T; Kitajima, Y

    1997-01-01

    Controversy exists about the histologic differences between hair follicle nevi and accessory tragi. We examined 10 congenital lesions histologically, possible diagnoses of which were hair follicle nevi or accessory tragi. Two specimens out of the 10 had tiny, mature hair follicles surrounded by thick fibrous root sheaths, a few fat cells, and no cartilage. The subcutaneous fat cells of their bases were segmented by a connective tissue framework. They had histologic features of hair follicle nevi. One specimen had cartilage and abundant fat cells with a connective tissue framework in the nodule, as well as a conglomeration of numerous well-differentiated hair follicles. It possessed both elements of a hair follicle nevus and an accessory tragus. Seven specimens had abundant subcutaneous fat and showed a prominent connective tissue framework. These were typical accessory tragi. The present study suggests that the number of fat cells in the nodule or papule differs between these two conditions. All the lesions studied revealed a connective tissue framework in the subcutaneous fat. Histologic features of both hair follicle nevi and accessory tragi can coexist in a single lesion. Hair follicle nevi may represent incomplete accessory tragi with scant fat cells.

  13. Wnt7b is an important intrinsic regulator of hair follicle stem cell homeostasis and hair follicle cycling.

    PubMed

    Kandyba, Eve; Kobielak, Krzysztof

    2014-04-01

    The hair follicle (HF) is an exceptional mini-organ to study the mechanisms which regulate HF morphogenesis, cycling, hair follicle stem cell (hfSCs) homeostasis, and progeny differentiation. During morphogenesis, Wnt signaling is well-characterized in the initiation of HF patterning but less is known about which particular Wnt ligands are required and whether individual Wnt ligands act in an indispensable or redundant manner during postnatal hfSCs anagen onset and HF cycle progression. Previously, we described the function of the bone morphogenetic protein (BMP) signaling target gene WNT7a in intrinsic regulation of hfSCs homeostasis in vivo. Here, we investigated the role of Wnt7b, which was also intrinsically upregulated in hfSCs during physiological and precocious anagen after BMP inhibition in vivo. We demonstrated Wnt7b to be a direct target of canonical BMP signaling in hfSCs and using Wnt7b conditional gene targeting during HF morphogenesis revealed disrupted HF cycling including a shorter anagen, premature catagen onset with overall shorter hair production, and diminished HF differentiation marker expression. Additionally, we observed that postnatal ablation of Wnt7b resulted in delayed HF activation, affecting both the hair germ and bulge hfSCs but still maintaining a two-step sequence of HF stimulation. Interestingly, Wnt7b cKO hfSCs participated in reformation of the new HF bulge, but with slower self-renewal. These findings demonstrate the importance of intrinsic Wnt7b expression in hfSCs regulation and normal HF cycling and surprisingly reveal a nonredundant role for Wnt7b in the control of HF anagen length and catagen entry which was not compensated by other Wnt ligands.

  14. Epithelial Wnt ligand secretion is required for adult hair follicle growth and regeneration.

    PubMed

    Myung, Peggy S; Takeo, Makoto; Ito, Mayumi; Atit, Radhika P

    2013-01-01

    β-Catenin, a key transducer molecule of Wnt signaling, is required for adult hair follicle growth and regeneration. However, the cellular source of Wnt ligands required for Wnt/β-catenin activation during anagen induction is unknown. In this study, we genetically deleted Wntless (Wls), a gene required for Wnt ligand secretion by Wnt-producing cells, specifically in the hair follicle epithelium during telogen phase. We show that epithelial Wnt ligands are required for anagen, as loss of Wls in the follicular epithelium resulted in a profound hair cycle arrest. Both the follicular epithelium and dermal papilla showed markedly decreased Wnt/β-catenin signaling during anagen induction compared with control hair follicles. Surprisingly, hair follicle stem cells that are responsible for hair regeneration maintained expression of stem cell markers but exhibited significantly reduced proliferation. Finally, we demonstrate that epidermal Wnt ligands are critical for adult wound-induced de novo hair formation. Collectively, these data show that Wnt ligands secreted by the hair follicle epithelium are required for adult hair follicle regeneration and provide new insight into potential cellular targets for the treatment of hair disorders such as alopecia.

  15. The advantages of hair follicle pluripotent stem cells over embryonic stem cells and induced pluripotent stem cells for regenerative medicine.

    PubMed

    Amoh, Yasuyuki; Katsuoka, Kensei; Hoffman, Robert M

    2010-12-01

    Multipotent adult stem cells have many potential therapeutic applications. Our recent findings suggest that hair follicles are a promising source of easily accessible multipotent stem cells. Stem cells in the hair follicle area express the neural stem cell marker nestin, suggesting that hair-follicle stem cells and neural stem cells have common features. Nestin-expressing hair follicle stem cells can form neurons and other cell types, and thus adult hair follicle stem cells could have important therapeutic applications, particularly for neurologic diseases. Transplanted hair follicle stem cells promote the functional recovery of injured peripheral nerve and spinal cord. Recent findings suggest that direct transplantation of hair-follicle stem cells without culture can promote nerve repair, which makes them potentially clinically practical. Human hair follicle stem cells as well as mouse hair follicle stem cells promote nerve repair and can be applied to test the hypothesis that human hair follicle stem cells can provide a readily available source of neurologically therapeutic stem cells. The use of hair follicle stem cells for nerve regeneration overcomes critical problems of embryonic stem cells or induced pluripotent stem cells in that the hair follicle stem cells are multipotent, readily accessible, non-oncogenic, and are not associated with ethical issues.

  16. Involvement of epithelial Wntless in the regulation of postnatal hair follicle morphogenesis.

    PubMed

    Huang, Sixia; Zhu, Xuming; Tao, Yixin; Sun, Qianqian; Wang, Lei; Li, Baojie; He, Lin; Guo, Xizhi; Ma, Gang

    2015-11-01

    The roles of the Wnt cargo receptor Wntless (Wls) during hair follicle (HF) induction and postnatal HF cycling in skin have been elucidated. However, whether Wls regulates postnatal HF morphogenesis remains unclear. In this study, we found that Wls is expressed in developing HF during the morphogenesis stage after birth. By knocking out Wls in mouse skin epithelia with hypomorphic K14-cre, we found that Wls is required for normal HF morphogenesis. Wls-deficient HFs prematurely regressed, which was possibly caused by abnormally activated TGF-β/JNK pathway. Although Wls was reported to be a direct target of the Wnt/β-catenin pathway, we found that epithelial β-catenin was not necessary to maintain Wls expression. Therefore, other signals are involved in regulating Wls transcription in mouse skin.

  17. Hair Follicle Bulge Stem Cells Appear Dispensable for the Acute Phase of Wound Re-epithelialization.

    PubMed

    Garcin, Clare L; Ansell, David M; Headon, Denis J; Paus, Ralf; Hardman, Matthew J

    2016-05-01

    The cutaneous healing response has evolved to occur rapidly, in order to minimize infection and to re-establish epithelial homeostasis. Rapid healing is achieved through complex coordination of multiple cell types, which importantly includes specific cell populations within the hair follicle (HF). Under physiological conditions, the epithelial compartments of HF and interfollicular epidermis remain discrete, with K15(+ve) bulge stem cells contributing progeny for HF reconstruction during the hair cycle and as a basis for hair shaft production during anagen. Only upon wounding do HF cells migrate from the follicle to contribute to the neo-epidermis. However, the identity of the first-responding cells, and in particular whether this process involves a direct contribution of K15(+ve) bulge cells to the early stage of epidermal wound repair remains unclear. Here we demonstrate that epidermal injury in murine skin does not induce bulge activation during early epidermal wound repair. Specifically, bulge cells of uninjured HFs neither proliferate nor appear to migrate out of the bulge niche upon epidermal wounding. In support of these observations, Diphtheria toxin-mediated partial ablation of K15(+ve) bulge cells fails to delay wound healing. Our data suggest that bulge cells only respond to epidermal wounding during later stages of repair. We discuss that this response may have evolved as a protective safeguarding mechanism against bulge stem cell exhaust and tumorigenesis. Stem Cells 2016;34:1377-1385.

  18. Hair Follicle Bulge Stem Cells Appear Dispensable for the Acute Phase of Wound Re‐epithelialization

    PubMed Central

    Garcin, Clare L.; Ansell, David M.; Headon, Denis J.; Paus, Ralf

    2016-01-01

    Abstract The cutaneous healing response has evolved to occur rapidly, in order to minimize infection and to re‐establish epithelial homeostasis. Rapid healing is achieved through complex coordination of multiple cell types, which importantly includes specific cell populations within the hair follicle (HF). Under physiological conditions, the epithelial compartments of HF and interfollicular epidermis remain discrete, with K15+ve bulge stem cells contributing progeny for HF reconstruction during the hair cycle and as a basis for hair shaft production during anagen. Only upon wounding do HF cells migrate from the follicle to contribute to the neo‐epidermis. However, the identity of the first‐responding cells, and in particular whether this process involves a direct contribution of K15+ve bulge cells to the early stage of epidermal wound repair remains unclear. Here we demonstrate that epidermal injury in murine skin does not induce bulge activation during early epidermal wound repair. Specifically, bulge cells of uninjured HFs neither proliferate nor appear to migrate out of the bulge niche upon epidermal wounding. In support of these observations, Diphtheria toxin‐mediated partial ablation of K15+ve bulge cells fails to delay wound healing. Our data suggest that bulge cells only respond to epidermal wounding during later stages of repair. We discuss that this response may have evolved as a protective safeguarding mechanism against bulge stem cell exhaust and tumorigenesis. Stem Cells 2016;34:1377–1385 PMID:26756547

  19. Hairless Streaks in Cattle Implicate TSR2 in Early Hair Follicle Formation

    PubMed Central

    Murgiano, Leonardo; Shirokova, Vera; Welle, Monika Maria; Jagannathan, Vidhya; Plattet, Philippe; Oevermann, Anna; Pienkowska-Schelling, Aldona; Gallo, Daniele; Gentile, Arcangelo; Mikkola, Marja; Drögemüller, Cord

    2015-01-01

    Four related cows showed hairless streaks on various parts of the body with no correlation to the pigmentation pattern. The stripes occurred in a consistent pattern resembling the lines of Blaschko. The non-syndromic hairlessness phenotype observed occurred across three generations of a single family and was compatible with an X-linked mode of inheritance. Linkage analysis and subsequent whole genome sequencing of one affected female identified two perfectly associated non-synonymous sequence variants in the critical interval on bovine chromosome X. Both variants occurred in complete linkage disequilibrium and were absent in more than 3900 controls. An ERCC6L missense mutation was predicted to cause an amino acid substitution of a non-conserved residue. Analysis in mice showed no specific Ercc6l expression pattern related to hair follicle development and therefore ERCC6L was not considered as causative gene. A point mutation at the 5'-splice junction of exon 5 of the TSR2, 20S rRNA accumulation, homolog (S. cerevisiae), gene led to the production of two mutant transcripts, both of which contain a frameshift and generate a premature stop codon predicted to truncate approximately 25% of the protein. Interestingly, in addition to the presence of both physiological TSR2 transcripts, the two mutant transcripts were predominantly detected in the hairless skin of the affected cows. Immunohistochemistry, using an antibody against the N-terminal part of the bovine protein demonstrated the specific expression of the TSR2 protein in the skin and the hair of the affected and the control cows as well as in bovine fetal skin and hair. The RNA hybridization in situ showed that Tsr2 was expressed in pre- and post-natal phases of hair follicle development in mice. Mammalian TSR2 proteins are highly conserved and are known to be broadly expressed, but their precise in vivo functions are poorly understood. Thus, by dissecting a naturally occurring mutation in a domestic animal

  20. Significant damage of the skin and hair following hair bleaching.

    PubMed

    Jeong, Mi-Sook; Lee, Chang-Moon; Jeong, Won-Ji; Kim, Seong-Jin; Lee, Ki-Young

    2010-10-01

    Scalp burns can be caused by hair bleaching with excess procedures such as unnecessary heating and excessive treatment with bleaching agents. The aim of this study was to investigate the morphological and histological changes of the hair and skin after bleaching. Ammonium persulfate and hydrogen peroxide (6% or 9%) solution mixed at a ratio of 1:2 (weight ratio) were sufficiently applied to human hairs and rat skin. The bleached hairs were brightened up to yellow by increasing the concentration of hydrogen peroxide and time of bleach treatment. After bleaching, scanning electron microscopy (SEM) was used to observe that the cuticle scales of the hairs were irregular and lifted. The mechanical properties of the bleached hairs, such as tensile strength and elongation, were slightly different than the untreated hairs. The tested rat skin showed severe swelling after treatment of the bleaching agent (9% hydrogen peroxide). The rat skin bleached with 9% hydrogen peroxide exhibited epidermal thinning and subepidermal vesicle formation. The extracellular matrix of the skin was seriously disrupted after bleaching. Therefore, the use of only suitable bleaching procedures is suggested in order to avoid injuries.

  1. The spatio-temporal domains of Frizzled6 action in planar polarity control of hair follicle orientation.

    PubMed

    Chang, Hao; Smallwood, Philip M; Williams, John; Nathans, Jeremy

    2016-01-01

    In mammals, hair follicles cover most of the body surface and exhibit precise and stereotyped orientations relative to the body axes. Follicle orientation is controlled by the planar cell polarity (PCP; or, more generally, tissue polarity) system, as determined by the follicle mis-orientation phenotypes observed in mice with PCP gene mutations. The present study uses conditional knockout alleles of the PCP genes Frizzled6 (Fz6), Vangl1, and Vangl2, together with a series of Cre drivers to interrogate the spatio-temporal domains of PCP gene action in the developing mouse epidermis required for follicle orientation. Fz6 is required starting between embryonic day (E)11.5 and E12.5. Eliminating Fz6 in either the anterior or the posterior halves of the embryo or in either the feet or the torso leads to follicle mis-orientation phenotypes that are limited to the territories associated with Fz6 loss, implying either that PCP signaling is required for communicating polarity information on a local but not a global scale, or that there are multiple independent sources of global polarity information. Eliminating Fz6 in most hair follicle cells or in the inter-follicular epidermis at E15.5 suggests that PCP signaling in developing follicles is not required to maintain their orientation. The asymmetric arrangement of Merkel cells around the base of each guard hair follicle dependents on Fz6 expression in the epidermis but not in differentiating Merkel cells. These experiments constrain current models of PCP signaling and the flow of polarity information in mammalian skin.

  2. Targeted expression of SV40 T antigen in the hair follicle of transgenic mice produces an aberrant hair phenotype.

    PubMed

    Keough, R; Powell, B; Rogers, G

    1995-03-01

    Directed expression of SV40 large T antigen (TAg) in transgenic mice can induce tissue-specific tumorigenesis and useful cell lines exhibiting differentiated characteristics can be established from resultant tumor cells. In an attempt to produce an immortalised mouse hair follicle cortical cell line for the study of hair keratin gene control, SV40 TAg expression was targeted to the hair follicles of transgenic mice using a sheep hair gene promoter. Expression of SV40 TAg in the follicle cortex disrupted normal fiber ultrastructure, producing a marked phenotypic effect. Affected hairs were wavy or severely kinked (depending on the severity of the phenotype) producing an appearance ranging from a ruffled coat to a stubble covering the back of the mouse. The transgenic hairs appeared to be weakened at the base of the fibers, leading to premature hair-loss and a thinner pelage, or regions of temporary nudity. No follicle tumors or neoplasia were apparent and immortalisation of cortical cells could not be established in culture. In situ hybridisation studies in the hair follicle using histone H3 as a cell proliferation marker suggested that cell proliferation had ceased prior to commencement of K2.10-TAg expression and was not re-established in the differentiating cortical cells. Hence, TAg was unable to induce cell immortalisation at that stage of cortical cell differentiation. However, transgenic mice developed various other abnormalities including vertebral abnormalities and bladder, liver and intestinal tumors, which resulted in reduced life expectancy.

  3. Promotion of hair growth by ginseng radix on cultured mouse vibrissal hair follicles.

    PubMed

    Matsuda, Hideaki; Yamazaki, Miho; Asanuma, Yusuke; Kubo, Michinori

    2003-08-01

    A 70% methanol extract from red ginseng (steamed and dried roots of Panax ginseng C. A. Meyer, a kind of Ginseng Radix) had superior activity to that of white ginseng (peeled and dried root of P. ginseng, another kind of Ginseng Radix) in a hair growth promoting assay using mouse vibrissal follicles in organ culture. Of the major constituents of P. ginseng, ginsenoside-Rb(1) (G-Rb(1)) exhibited activity, but ginsenoside-Rg(1) (G-Rg(1)) and -Ro (G-Ro) were ineffective. Additionally, 20(S)-ginsenoside-Rg(3) (20(S)-G-Rg(3)) formed by the processing of red ginseng from the crude root of P. ginseng also showed hair growth promoting activity. These results indicate that Ginseng Radix possesses hair growth promoting activity, and its bioactive components are partially attributable to the ginseng saponin components mentioned above.

  4. SCF/c-kit signaling is required in 12-O-tetradecanoylphorbol-13-acetate-induced migration and differentiation of hair follicle melanocytes for epidermal pigmentation.

    PubMed

    Qiu, Weiming; Yang, Ke; Lei, Mingxing; Yan, Hongtao; Tang, Hui; Bai, Xiufeng; Yang, Guihong; Lian, Xiaohua; Wu, Jinjin

    2015-05-01

    Hair follicle melanocyte stem cells (McSCs) are responsible for hair pigmentation and also function as a major melanocyte reservoir for epidermal pigmentation. However, the molecular mechanism promoting McSCs for epidermal pigmentation remains elusive. 12-O-tetradecanoylphorbol-13-acetate (TPA) mimics key signaling involved in melanocyte growth, migration and differentiation. We therefore investigated the molecular basis for the contribution of hair follicle McSCs to epidermal pigmentation using the TPA induction model. We found that repetitive TPA treatment of female C57BL/6 mouse dorsal skin induced epidermal pigmentation by increasing the number of epidermal melanocytes. Particularly, TPA treatment induced McSCs to initiate proliferation, exit the stem cell niche and differentiate. We also demonstrated that TPA promotes melanoblast migration and differentiation in vitro. At the molecular level, TPA treatment induced robust expression of stem cell factor (SCF) in keratinocytes and c-kit in melanoblasts and melanocytes. Administration of ACK2, a neutralizing antibody against the Kit receptor, suppressed mouse epidermal pigmentation, decreased the number of epidermal melanocytes, and inhibited melanoblast migration. Taken together, our data demonstrate that TPA promotes the expansion, migration and differentiation of hair follicle McSCs for mouse epidermal pigmentation. SCF/c-kit signaling was required for TPA-induced migration and differentiation of hair follicle melanocytes. Our findings may provide an excellent model to investigate the signaling mechanisms regulating epidermal pigmentation from mouse hair follicle McSCs, and a potential therapeutic option for skin pigmentation disorders.

  5. Shh expression is required for embryonic hair follicle but not mammary gland development.

    PubMed

    Michno, Kinga; Boras-Granic, Kata; Mill, Pleasantine; Hui, C C; Hamel, Paul A

    2003-12-01

    The embryonic mammary gland and hair follicle are both derived from the ventral ectoderm, and their development depends on a number of common fundamental developmental pathways. While the Hedgehog (Hh) signaling pathway is required for hair follicle morphogenesis, the role of this pathway during embryonic mammary gland development remains undetermined. We demonstrate here that, unlike the hair follicle, both Shh and Ihh are expressed in the developing embryonic mouse mammary rudiment as early as E12.5. In Shh(-/-) embryos, hair follicle development becomes arrested at an early stage, while the mammary rudiment, which continues to express Ihh, develops in a manner indistinguishable from that of wild-type littermates. The five pairs of mammary buds in Shh(-/-) female embryos exhibit normal branching morphogenesis at E16.5, forming a rudimentary ductal structure identical to wild-type embryonic mammary glands. We further demonstrate that loss of Hh signaling causes altered cyclin D1 expression in the embryonic dermal mesenchyme. Specifically, cyclin D1 is expressed at E14.5 principally in the condensed mesenchymal cells of the presumptive hair follicles and in both mesenchymal and epithelial cells of the mammary rudiments in wild-type and Shh-deficient embryos. By E18.5, robust cyclin D1 expression is maintained in mammary rudiments of both wild-type and Shh-deficient embryos. In hair follicles of wild-type embryos by E18.5, cyclin D1 expression switches to follicular epithelial cells. In contrast, strong cyclin D1 expression is observed principally in the mesenchymal cells of arrested hair follicles in Shh(-/-) embryos at E18.5. These data reveal that, despite the common embryonic origin of hair follicles and mammary glands, distinct patterns of Hh-family expression occur in these two tissues. Furthermore, these data suggest that cyclin D1 expression in the embryonic hair follicle is mediated by both Hh-independent and Hh-dependent mechanisms.

  6. Morphological analysis of the growth stages of in-vivo mouse hair follicles by using optical coherence tomography

    NASA Astrophysics Data System (ADS)

    Jha, Rakesh Kumar; Kim, Kanghae; Jeon, Mansik; Kim, Jeehyun; Kang, Minyoung; Han, Insook; Kim, Moonkyu

    2016-09-01

    Swept-source optical coherence tomography (SS-OCT), a bio-photonic imaging modality, was used to demonstrate an initial feasibility experiment for detecting morphological variations of in-vivo mouse hair follicles for the anagen and the telogen growth stages. Two C57BL/6 adult male mice, one undergoing the anagen stage and the other undergoing the telogen stage of the hair follicle growth cycle, were selected for the experiment. The OCT cross-sectional images of mice skin were acquired in-vivo within an interval of 15 days, and the observed morphological changes were analyzed. The micro-structural features of mice skin on the 15th experimental day were further compared with corresponding histological observations. The preliminary result of this study provides clear insights into the structural details of mouse skin, confirming the resemblance of the OCT images with the corresponding histological measurements, and ensures the suitability of SS-OCT for non-invasive analysis of hair follicle conditions.

  7. Delineating immune-mediated mechanisms underlying hair follicle destruction in the mouse mutant defolliculated.

    PubMed

    Ruge, Fiona; Glavini, Aikaterini; Gallimore, Awen M; Richards, Hannah E; Thomas, Christopher P; O'Donnell, Valerie B; Philpott, Michael P; Porter, Rebecca M

    2011-03-01

    Defolliculated (Gsdma3(Dfl)/+) mice have a hair loss phenotype that involves an aberrant hair cycle, altered sebaceous gland differentiation with reduced sebum production, chronic inflammation, and ultimately the loss of the hair follicle. Hair loss in these mice is similar to that seen in primary cicatricial, or scarring alopecias in which immune targeting of hair follicle stem cells has been proposed as a key factor resulting in permanent hair follicle destruction. In this study we examine the mechanism of hair loss in GsdmA3(Dfl)/+ mice. Aberrant expression patterns of stem cell markers during the hair cycle, in addition to aberrant behavior of the melanocytes leading to ectopic pigmentation of the hair follicle and epidermis, indicated the stem cell niche was not maintained. An autoimmune mechanism was excluded by crossing the mice with rag1-/- mice. However, large numbers of macrophages and increased expression of ICAM-1 were still present and may be involved either directly or indirectly in the hair loss. Reverse transcriptase-PCR (RT-PCR) and immunohistochemistry of sebaceous gland differentiation markers revealed reduced peroxisome proliferator-activated receptor-γ (PPARγ), a potential cause of reduced sebum production, as well as the potential involvement of the innate immune system in the hair loss. As reduced PPARγ expression has recently been implicated as a cause for lichen planopilaris, these mice may be useful for testing therapies.

  8. Protection against chemotherapy-induced alopecia: targeting ATP-binding cassette transporters in the hair follicle?

    PubMed

    Haslam, Iain S; Pitre, Aaron; Schuetz, John D; Paus, Ralf

    2013-11-01

    Currently, efficacious treatments for chemotherapy-induced alopecia (hair loss) are lacking, and incidences of permanent hair loss following high-dose chemotherapy are on the increase. In this article, we describe mechanisms by which the pharmacological defense status of the hair follicle might be enhanced, thereby reducing the accumulation of cytotoxic cancer drugs and preventing or reducing hair loss and damage. We believe this could be achieved via the selective increase in ATP-binding cassette (ABC) transporter expression within the hair follicle epithelium, following application of topical agonists for regulatory nuclear receptors. Clinical application would require the development of hair follicle-targeted formulations, potentially utilizing nanoparticle technology. This novel approach has the potential to yield entirely new therapeutic options for the treatment and management of chemotherapy-induced alopecia, providing significant psychological and physical benefit to cancer patients.

  9. Regenerative metamorphosis in hairs and feathers: follicle as a programmable biological printer

    PubMed Central

    Oh, Ji Won; Lin, Sung-Jan; Plikus, Maksim V.

    2015-01-01

    Present-day hairs and feathers are marvels of biological engineering perfected over 200 million years of convergent evolution. Prominently, both follicle types coevolved regenerative cycling, wherein active filament making (anagen) is intermitted by a phase of relative quiescence (telogen). Such regenerative cycling enables follicles to “reload” their morphogenetic program and make qualitatively different filaments in the consecutive cycles. Indeed, many species of mammals and birds undergo regenerative metamorphosis, prominently changing their integument between juvenile and adult forms. This phenomenon is inconspicuous in mice, which led to the conventional perception that hair type is hardwired during follicle morphogenesis and cannot switch. A series of recent works by Chi and Morgan change this perception, and show that many mouse follicles naturally switch hair morphologies, for instance from “wavy” zigzag to straight awl, in the second growth cycle. A series of observations and genetic experiments show that back and forth hair type switching depends on the number of cells in the follicle's dermal papilla, with the critical threshold being around 40-50 cells. Pigmentation is another parameter that hair and feather follicles can reload between cycles, and even midway through anagen. Recent works show that hair and feather pigmentation “printing” programs coevolved to rely on pulsed expression of Agouti, a melanocortin receptor-1 antagonist, in the follicular mesenchyme. Here, we discuss broader implications of hair and feather regenerative plasticity. PMID:25557541

  10. The in vitro use of the hair follicle closure technique to study the follicular and percutaneous permeation of topically applied drugs.

    PubMed

    Stahl, Jessica; Niedorf, Frank; Wohlert, Mareike; Kietzmann, Manfred

    2012-03-01

    Recent studies on follicular permeation emphasise the importance of hair follicles as diffusion pathways, but only a limited amount of data are available about the follicular permeation of topically applied drugs. This study examines the use of a hair follicle closure technique in vitro, to determine the participation of hair follicles in transdermal drug penetration. Various substances, with different lipophilicities, were tested: caffeine, diclofenac, flufenamic acid, ibuprofen, paracetamol, salicylic acid and testosterone. Diffusion experiments were conducted with porcine skin, the most common replacement material for human skin, in Franz-type diffusion cells over 28 hours. Different experimental settings allowed the differentiation between interfollicular and follicular permeation after topical application of the test compounds. A comparison of the apparent permeability coefficients of the drugs demonstrates that the percutaneous permeations of caffeine and flufenamic acid were significantly higher along the hair follicles. In the cases of paracetamol and testosterone, the follicular pathway appears to be of importance, while no difference was found between interfollicular and follicular permeation for diclofenac, ibuprofen and salicylic acid. Thus, the hair follicle closure technique represents an adequate in vitro method for gaining information about follicular or percutaneous permeation, and can replace in vivo testing in animals or humans.

  11. Sgk3 links growth factor signaling to maintenance of progenitor cells in the hair follicle.

    PubMed

    Alonso, Laura; Okada, Hitoshi; Pasolli, Hilda Amalia; Wakeham, Andrew; You-Ten, Annick Itie; Mak, Tak W; Fuchs, Elaine

    2005-08-15

    Tyrosine kinase growth factor receptor signaling influences proliferation, survival, and apoptosis. Hair follicles undergo cycles of proliferation and apoptotic regression, offering an excellent paradigm to study how this transition is governed. Several factors are known to affect the hair cycle, but it remains a mystery whether Akt kinases that are downstream of growth factor signaling impact this equilibrium. We now show that an Akt relative, Sgk (serum and glucocorticoid responsive kinase) 3, plays a critical role in this process. Hair follicles of mice lacking Sgk3 fail to mature normally. Proliferation is reduced, apoptosis is increased, and follicles prematurely regress. Maintenance of the pool of transiently amplifying matrix cells is impaired. Intriguingly, loss of Sgk3 resembles the gain of function of epidermal growth factor signaling. Using cultured primary keratinocytes, we find that Sgk3 functions by negatively regulating phosphatidylinositol 3 kinase signaling. Our results reveal a novel and important function for Sgk3 in controlling life and death in the hair follicle.

  12. Point scanning confocal microscopy facilitates 3D human hair follicle imaging in tissue sections.

    PubMed

    Kloepper, Jennifer E; Bíró, Tamás; Paus, Ralf; Cseresnyés, Zoltán

    2010-07-01

    Efficiency is a key factor in determining whether a scientific method becomes widely accepted in practical applications. In dermatology, morphological characterisation of intact hair follicles by traditional methods can be rather inefficient. Samples are embedded, sliced, imaged and digitally reconstructed, which can be time-consuming. Confocal microscopy, on the other hand, is more efficient and readily applicable to study intact hair follicles. Modern confocal microscopes deliver and collect light very efficiently and thus allow high spatial resolution imaging of relatively thick samples. In this letter, we report that we successfully imaged entire intact human hair follicles using point scanning confocal microscopy. Light delivery and light-collection were further improved by preparing the samples in 2,2'-Thiodiethanol (TDE), thus reducing refractive index gradients. The relatively short total scan times and the high quality of the acquired 3D images make confocal microscopy a desirable method for studying intact hair follicles under normal and pathological conditions.

  13. Variability of hair coat and skin traits as related to adaptation in Criollo Limonero cattle.

    PubMed

    Landaeta-Hernández, Antonio; Zambrano-Nava, Sunny; Hernández-Fonseca, Juan P; Godoy, Rosario; Calles, Marcos; Iragorri, José L; Añez, Lauderys; Polanco, Miguel; Montero-Urdaneta, Merilio; Olson, Tim

    2011-03-01

    The variation in hair coat and skin histology traits of Criollo Limonero cattle was analyzed using 213 Criollo Limonero females. Skin biopsies were obtained from slick-haired (N=16) and normal-haired (N=14) animals. Measured traits included hair length (HL), color coat (CC), number of hair follicles per square centimeter (NHF), sweat glands per square centimeter (NSG), sweat glands size (SGS), sebaceous glands per square centimeter (NSBG), blood vessels per square centimeter (NBV), and thickness of epidermis (TE). Hair length differed (P<0.001) between slick- and normal-haired animals (4.9 ± 0.12 vs 10.9 ± 0.20, respectively). Differences (P<0.01) in CC (Bayo = 144/67.6% vs Red = 69/32.4%) and HL (slick-haired = 199/93.4% vs normal-haired = 14/6.5%) were found. Distribution of slick- and normal-haired animals differed (P<0.01) between bayo-coated and red-coated (139/62.2% vs 9/4.2%; respectively). Most (P<0.05) red-coated animals belonged to a single family. No differences (P>0.05) were found between slick-haired and normal-haired animals in NHF (637 ± 164 vs 587 ± 144, respectively), NSG (556 ± 134 vs 481 ± 118, respectively), NSBG (408 ± 87 vs 366 ± 77, respectively), NBV (1628 ± 393 vs 1541 ± 346, respectively), and TE (1.24 ± 0.14 vs 1.32 ± 0.12, respectively). However, SGS was greater (P<0.01) in slick-haired than normal-haired animals. In conclusion, Criollo Limonero cattle are predominantly bayo-coated, slick-haired, with a reduced number of hair follicles relative to Zebu cattle, sweat and sebaceous glands in proportion to hair follicle numbers, and with a high blood flow irrigating the skin. There is a sub-group of red-coated animals with yellow or cream skin, thicker epidermis, and with a higher frequency of normal-haired animals. It appears that the slick hair gene has been favored by natural selection in this breed.

  14. Disruption of the hedgehog signaling pathway contributes to the hair follicle cycling deficiency in Vdr knockout mice.

    PubMed

    Teichert, Arnaud; Elalieh, Hashem; Bikle, Daniel

    2010-11-01

    Mice null for the Vitamin D receptor (VdrKO) have a disrupted first hair follicle cycle and aborted subsequent hair follicle cycling. We examined the expression of different markers and mediators of hair follicle cycling in the hair follicle of the VdrKO mouse during days 13-22 when the hair follicle normally initiates and completes the first catagen. We compared the expression of those genes in mice with a nonsense mutation in hairless (Rhino), which have a similar alopecia phenotype, and to Cyp27b1 null mice which are deficient in the production of 1,25(OH)2D3, the Vdr ligand, but display normal hair follicle cycling. Our results demonstrate the down regulation of hair follicle markers and the alteration of expression of hedgehog (Hh), Wnt, Fgf, and Tgfbeta pathways in VdrKO and Rhino mice, but not in Cyp27b1KO mice. Treatment of VdrKO mice with an agonist to the Hh pathway partially restored hair follicle cycling, suggesting a role of this pathway in the regulation of hair follicle cycling by VDR. These results suggest that Vdr regulates directly or indirectly the expression of genes required for hair follicle cycling, including Hh signaling, independent of 1,25(OH)2D3.

  15. Skin Exposures & Effects in the Workplace

    MedlinePlus

    ... through the corneocytes. Figure 3: Through the appendages (hair follicles, glands) As shown in Figure 3, the third ... through the skin is skin appendages (i.e., hair follicles and glands). This pathway is usually insignificant because ...

  16. Just the Facts: Skin and Hair Problems on Dialysis

    MedlinePlus

    Just the Facts: Skin and Hair Problems on Dialysis How does dialysis affect my skin? Many people on dialysis have skin changes. The skin may seem more ... treated by a skin specialist. Why is my hair falling out? Hair is made of protein. If ...

  17. Dendritic polyglycerol and N-isopropylacrylamide based thermoresponsive nanogels as smart carriers for controlled delivery of drugs through the hair follicle.

    PubMed

    Sahle, Fitsum Feleke; Giulbudagian, Michael; Bergueiro, Julian; Lademann, Jürgen; Calderón, Marcelo

    2017-01-07

    Nanoparticles with a size of several hundred nanometers can effectively penetrate into the hair follicles and may serve as depots for controlled drug delivery. However, they can neither overcome the hair follicle barrier to reach the viable cells nor release the loaded drug adequately. On the other hand, small drug molecules cannot penetrate deep into the hair follicles. Thus, the most efficient way for drug delivery through the follicular route is to employ nanoparticles that can release the drug close to the target structure upon exposure to some external or internal stimuli. Accordingly, 100-700 nm sized thermoresponsive nanogels with a phase transition temperature of 32-37 °C were synthesized by the precipitation polymerization technique using N-isopropylacrylamide as a monomer, acrylated dendritic polyglycerol as a crosslinker, VA-044 as an initiator, and sodium dodecyl sulphate as a stabilizer. The follicular penetration of the indodicarbocyanine (IDCC) labeled nanogels into the hair follicles and the release of coumarin 6, which was loaded as a model drug, in the hair follicles were assessed ex vivo using porcine ear skin. Confocal laser scanning microscopy (CLSM) enabled independent tracking of the nanogels and the loaded dye, although it is not as precise and accurate as standard analytical methods. The results showed that, unlike smaller nanogels (<100 nm), medium and larger sized nanogels (300-500 nm) penetrated effectively into the hair follicles with penetration depths proportional to the nanogel size. The release of the loaded dye in the hair follicles increased significantly when the investigation on penetration was carried out above the cloud point temperature of the nanogels. The follicular penetration of the nanogels from the colloidal dispersion and a 2.5% hydroxyethyl cellulose gel was not significantly different.

  18. Hair Follicle Stem Cell-Specific PPARγ Deletion Causes Scarring Alopecia

    PubMed Central

    Karnik, Pratima; Tekeste, Zenar; McCormick, Thomas S.; Gilliam, Anita C.; Price, Vera H.; Cooper, Kevin D.; Mirmirani, Paradi

    2010-01-01

    Primary cicatricial or scarring alopecias (CA) are a group of inflammatory hair disorders of unknown pathogenesis characterized by the permanent destruction of the hair follicle. The current treatment options are ineffective in controlling disease progression largely because the molecular basis for CA is not understood. Microarray analysis of the lymphocytic CA, Lichen planopilaris (LPP), compared to normal scalp biopsies identified decreased expression of genes required for lipid metabolism and peroxisome biogenesis. Immunohistochemical analysis showed progressive loss of peroxisomes, proinflammatory lipid accumulation, and infiltration of inflammatory cells followed by destruction of the pilosebaceous unit. The expression of peroxisome proliferator-activated receptor (PPAR) γ, a transcription factor that regulates these processes, is significantly decreased in LPP. Specific agonists of PPARγ are effective in inducing peroxisomal and lipid metabolic gene expression in human keratinocytes. Finally, targeted deletion of PPARγ in follicular stem cells in mice causes a skin and hair phenotype that emulates scarring alopecia. These studies suggest that PPARγ is crucial for healthy pilosebaceous units and it is the loss of this function that triggers the pathogenesis of LPP. We propose that PPARγ-targeted therapy may represent a new strategy in the treatment of these disorders. PMID:19052558

  19. Hair follicle: a novel source of multipotent stem cells for tissue engineering and regenerative medicine.

    PubMed

    Mistriotis, Panagiotis; Andreadis, Stelios T

    2013-08-01

    The adult body harbors powerful reservoirs of stem cells that enable tissue regeneration under homeostatic conditions or in response to disease or injury. The hair follicle (HF) is a readily accessible mini organ within the skin and contains stem cells from diverse developmental origins that were shown to have surprisingly broad differentiation potential. In this review, we discuss the biology of the HF with particular emphasis on the various stem cell populations residing within the tissue. We summarize the existing knowledge on putative HF stem cell markers, the differentiation potential, and technologies to isolate and expand distinct stem cell populations. We also discuss the potential of HF stem cells for drug and gene delivery, tissue engineering, and regenerative medicine. We propose that the abundance of stem cells with broad differentiation potential and the ease of accessibility makes the HF an ideal source of stem cells for gene and cell therapies.

  20. Basal cell carcinoma preferentially arises from stem cells within hair follicle and mechanosensory niches.

    PubMed

    Peterson, Shelby C; Eberl, Markus; Vagnozzi, Alicia N; Belkadi, Abdelmadjid; Veniaminova, Natalia A; Verhaegen, Monique E; Bichakjian, Christopher K; Ward, Nicole L; Dlugosz, Andrzej A; Wong, Sunny Y

    2015-04-02

    Basal cell carcinoma (BCC) is characterized by frequent loss of PTCH1, leading to constitutive activation of the Hedgehog pathway. Although the requirement for Hedgehog in BCC is well established, the identity of disease-initiating cells and the compartments in which they reside remain controversial. By using several inducible Cre drivers to delete Ptch1 in different cell compartments in mice, we show here that multiple hair follicle stem cell populations readily develop BCC-like tumors. In contrast, stem cells within the interfollicular epidermis do not efficiently form tumors. Notably, we observed that innervated Gli1-expressing progenitors within mechanosensory touch dome epithelia are highly tumorigenic. Sensory nerves activate Hedgehog signaling in normal touch domes, while denervation attenuates touch dome-derived tumors. Together, our studies identify varying tumor susceptibilities among different stem cell populations in the skin, highlight touch dome epithelia as "hot spots" for tumor formation, and implicate cutaneous nerves as mediators of tumorigenesis.

  1. Topical cyclosporin induces hair growth in human split skin grafted onto nude mice.

    PubMed

    Gilhar, A; Etzioni, A; Moscona, R

    1991-01-01

    Previously we observed that systemic CyA induces hair growth in an experimental model of human scalp skin graft transplanted onto nude mice. In the present study we investigated the role of topical CyA in the murine transplantation model, using human split-thickness skin grafts (HSTSG). Ten mice grafted with 1-mm-thick skin and another 10 mice grafted with 0.4-mm-thick skin were treated topically with CyA in olive oil. Ten other mice, treated with olive oil only, served as a control group. At the end of the study we observed hair growth only on the grafted skin of the CyA-treated group. Four out of 10 grafts showed hair growth in each of the groups. Quantitative analysis of transverse sections of cylindrical punch biopsy specimens of HSTSG before transplantation revealed anagen follicles, including small ones and telogen/catagen follicles, whereas specimens after skin transplantation showed terminal follicles mostly in the anagen phase. The present study provides further support to previous observations regarding the beneficial effect of CyA on hair growth.

  2. Pterins in human hair follicle cells and in the synchronized murine hair cycle.

    PubMed

    Schallreuter, K U; Beazley, W D; Hibberts, N A; Tobin, D J; Paus, R; Wood, J M

    1998-10-01

    Human dermal papilla cells (HDPC) express mRNA for the key enzymes for de novo synthesis/recycling and regulation of the pterin (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin (6BH4). HDPC had significantly higher enzyme activities and 6BH4 levels in a comparative study with dermal fibroblasts, epidermal melanocytes, and keratinocytes under in vitro conditions. In addition, a significantly more rapid uptake of 14C-L-phenylalanine was demonstrated in HDPC compared with fibroblasts, whereas the differences in turnover to L-tyrosine were insignificant, suggesting a pooling of L-phenylalanine in HDPC. These results suggested that HDPC driven 6BH4 synthesis could be of major functional importance in the hair cycle. In order to follow this hypothesis in vivo, expression of enzyme activities and levels of the produced cofactor during the synchronized hair cycle were determined employing the murine model C57BL/6. These data revealed a significantly increased de novo synthesis for 6BH4 via GTP-cyclohydrolase I concomitant with high levels of 6BH4, and the induction of phenylalanine hydroxylase activities during the telogen/early anagen stage (days 0-1). Pterin levels and enzyme activities fall on day 3 and plateau during the rest of the entire cycle. In addition, thioredoxin reductase and glutathione reductase activities were measured, where the latter enzyme remained constant but thioredoxin reductase activities showed a biphasic behavior. The first peak coincided with the induction of 6BH4 de novo synthesis at the beginning of the hair cycle. The second peak was observed at mid-anagen, when melanogenesis takes place. Taken together, our results show the presence of autocrine pterin synthesis/recycling in human hair follicle cells under in vitro conditions, and a possible role for 6BH4 in the synchronized murine hair cycle.

  3. GENE EXPRESSION IN HEAD HAIR FOLLICLES PLUCKED FROM MEN AND WOMEN

    EPA Science Inventory

    Characterizing gene expression in hair follicles can help to elucidate the hair growth cycle by delineating the genes and pathways involved in follicular growth and degeneration. The objectives of this study were to determine whether intact RNA could be extracted from a small num...

  4. Managing the hair and skin of African American pediatric patients.

    PubMed

    Smith, W; Burns, C

    1999-01-01

    In Africa, the ancestral home of most African Americans, hair is viewed as the epitome of beauty. However, when Africans were brought to America as slaves, they were unable to care for their hair and skin adequately and were exposed to the predominant white culture, which valued straight hair and light skin. As a result, many African Americans lost self-esteem because of the characteristics of their hair and skin. In this article we examine the anatomic and physiologic features of African American hair and skin and typical African American hair and skin care practices. Common African American hair and skin disorders and their management are discussed. The goal of this article is to help primary care providers understand the special hair and skin care required for African American children (as well as other dark-skinned patients). With good patient education, understanding one's own hair and skin characteristics can also support positive self-esteem.

  5. Serum response factor controls transcriptional network regulating epidermal function and hair follicle morphogenesis.

    PubMed

    Lin, Congxing; Hindes, Anna; Burns, Carole J; Koppel, Aaron C; Kiss, Alexi; Yin, Yan; Ma, Liang; Blumenberg, Miroslav; Khnykin, Denis; Jahnsen, Frode L; Crosby, Seth D; Ramanan, Narendrakumar; Efimova, Tatiana

    2013-03-01

    Serum response factor (SRF) is a transcription factor that regulates the expression of growth-related immediate-early, cytoskeletal, and muscle-specific genes to control growth, differentiation, and cytoskeletal integrity in different cell types. To investigate the role for SRF in epidermal development and homeostasis, we conditionally knocked out SRF in epidermal keratinocytes. We report that SRF deletion disrupted epidermal barrier function leading to early postnatal lethality. Mice lacking SRF in epidermis displayed morphogenetic defects, including an eye-open-at-birth phenotype and lack of whiskers. SRF-null skin exhibited abnormal morphology, hyperplasia, aberrant expression of differentiation markers and transcriptional regulators, anomalous actin organization, enhanced inflammation, and retarded hair follicle (HF) development. Transcriptional profiling experiments uncovered profound molecular changes in SRF-null E17.5 epidermis and revealed that many previously identified SRF target CArG box-containing genes were markedly upregulated in SRF-null epidermis, indicating that SRF may function to repress transcription of a subset of its target genes in epidermis. Remarkably, when transplanted onto nude mice, engrafted SRF-null skin lacked hair but displayed normal epidermal architecture with proper expression of differentiation markers, suggesting that although keratinocyte SRF is essential for HF development, a cross-talk between SRF-null keratinocytes and the surrounding microenvironment is likely responsible for the barrier-deficient mutant epidermal phenotype.

  6. Wnt5a Suppresses β-catenin Signaling during Hair Follicle Regeneration

    PubMed Central

    Xing, Yizhan; Ma, Xiaogen; Guo, Haiying; Deng, Fang; Yang, Jin; Li, Yuhong

    2016-01-01

    Hair follicles display periodic growth. Wnt signaling is a critical regulator for hair follicle regeneration. Previously, we reported that Wnt5a inhibits the telogen-to-anagen transition of hair follicles, but the mechanism by which this process occurs has not yet been reported. Here, we determined the expression patterns of Wnt signaling pathway molecules by quantitative reverse transcription polymerase chain reaction, western blot, and immunohistochemistry and found that β-catenin signaling was suppressed by Wnt5a. We then compared the phenotypes and expression patterns following β-catenin knockdown and Wnt5a overexpression during hair follicle regeneration induced by hair depilation and observed similar patterns. In addition, we performed a rescue experiment in the JB6 cell line and found that the inhibitory effect of Wnt5a on cell proliferation could be rescued by the addition of Wnt3a. Our data reveal that Wnt5a suppresses the activation of β-catenin signaling during hair follicle regeneration. PMID:27499692

  7. A new hair follicle-derived human epidermal model for the evaluation of sunscreen genoprotection.

    PubMed

    Bacqueville, D; Douki, T; Duprat, L; Rebelo-Moreira, S; Guiraud, B; Dromigny, H; Perier, V; Bessou-Touya, S; Duplan, H

    2015-10-01

    Induction of skin cancer is the most deleterious effect of excessive exposure to sunlight. Accurate evaluation of sunscreens to protect the genome is thus of major importance. In particular, the ability of suncare products to prevent the formation of DNA damage should be evaluated more directly since the Sun Protection Factor is only related to erythema induction. For this purpose, we developed an in vitro approach using a recently characterized reconstituted human epidermis (RHE) model engineered from hair follicle. The relevance of this skin substitute in terms of UV-induced genotoxicity was compared to ex vivo explants exposed to solar-simulated radiation (SSR). The yield of bipyrimidine photoproducts, their rate of repair, and the induction of apoptosis were very similar in both types of skin samples. In order to evaluate the protection afforded by sunscreen against DNA damage, bipyrimidine photoproducts were quantified in tissue models following SSR exposure in the presence or absence of a SPF50+ formula. A rather high DNA protection factor of approximately 20 was found in RHE, very similar to that determined for explants. Thus, RHE is a good surrogate to human skin, and also a convenient and useful tool for investigation of the genoprotection of sunscreens.

  8. Penetration profile of microspheres in follicular targeting of terminal hair follicles.

    PubMed

    Toll, R; Jacobi, U; Richter, H; Lademann, J; Schaefer, H; Blume-Peytavi, U

    2004-07-01

    The transfollicular administration of pharmacologically active molecules is of current therapeutic interest, mainly with regard to delivery to specific sites of the hair follicle (HF) and the reduction of hepatic metabolism and systemic toxicity. HF are privileged pathways for specific molecules depending on formulations, which enter faster into these shunts than through the stratum corneum. The aim was to optimize the delivery of fluorescent microspheres into the HF, thereby, developing a standardized protocol for follicular targeting with microspheres. The number of HF showing penetration, as well as the depth of penetration, was determined. Freshly excised skin samples with terminal HF were divided into groups, with or without prior treatment with cyanoacrylate skin surface stripping-technique (CSSS). Thereafter microspheres at a size of 0.75-6.0 microm were applied according to the developed standardized protocol. Skin biopsies were obtained, shock-frozen, and sectioned in 5 microm slices. We demonstrated a selective penetration route of the microspheres into the HF. Optimal microsphere size proved to be approximately 1.5 microm, with a 55% rate of all HF, and with a maximum penetration depth of >2300 microm. Without previous CSSS treatment of the skin, the transfollicular microsphere penetration was below 27% with a maximum penetration depth of 1000 microm. Thus, the basis for follicular targeting of essential structures containing stem cells for keratinocytes, melanocytes, and mast cells has been laid.

  9. Potassium channel openers stimulate DNA synthesis in mouse epidermal keratinocyte and whole hair follicle cultures.

    PubMed

    Harmon, C S; Lutz, D; Ducote, J

    1993-01-01

    We have conducted studies using primary mouse epidermal keratinocyte and whole hair follicle cultures to investigate the mechanism of the hypertrichotic activity of potassium channel openers. In a time course study, the extent of stimulation of epidermal keratinocyte DNA synthesis by minoxidil increased as the rate of DNA synthesis in control cultures declined. Minoxidil stimulation of DNA synthesis in 7-day cultures required prolonged (> 1 day) exposure to the agent. Pinacidil and diazoxide also stimulated DNA synthesis in mouse epidermal keratinocyte cultures. In addition, minoxidil, pinacidil, diazoxide, and cromakalim stimulated DNA synthesis in whole-organ cultures of mouse hair follicles. These results suggest that potassium channel openers retard the loss of proliferative activity of differentiating keratinocytes and support the hypothesis that these agents stimulate hair growth through a direct effect on hair follicles.

  10. Matriptase/MT-SP1 is required for postnatal survival, epidermal barrier function, hair follicle development, and thymic homeostasis.

    PubMed

    List, Karin; Haudenschild, Christian C; Szabo, Roman; Chen, WanJun; Wahl, Sharon M; Swaim, William; Engelholm, Lars H; Behrendt, Niels; Bugge, Thomas H

    2002-05-23

    Matriptase/MT-SP1 is a novel tumor-associated type II transmembrane serine protease that is highly expressed in the epidermis, thymic stroma, and other epithelia. A null mutation was introduced into the Matriptase/MT-SP1 gene of mice to determine the role of Matriptase/MT-SP1 in epidermal development and neoplasia. Matriptase/MT-SP1-deficient mice developed to term but uniformly died within 48 h of birth. All epidermal surfaces of newborn mice were grossly abnormal with a dry, red, shiny, and wrinkled appearance. Matriptase/MT-SP1-deficiency caused striking malformations of the stratum corneum, characterized by dysmorphic and pleomorphic corneocytes and the absence of vesicular bodies in transitional layer cells. This aberrant skin development seriously compromised both inward and outward epidermal barrier function, leading to the rapid and fatal dehydration of Matriptase/MT-SP1-deficient pups. Loss of Matriptase/MT-SP1 also seriously affected hair follicle development resulting in generalized follicular hypoplasia, absence of erupted vibrissae, lack of vibrissal hair canal formation, ingrown vibrissae, and wholesale abortion of vibrissal follicles. Furthermore, Matriptase/MT-SP1-deficiency resulted in dramatically increased thymocyte apoptosis, and depletion of thymocytes. This study demonstrates that Matriptase/MT-SP1 has pleiotropic functions in the development of the epidermis, hair follicles, and cellular immune system.

  11. THE ELECTRON MICROSCOPY OF THE HUMAN HAIR FOLLICLE

    PubMed Central

    Birbeck, M. S. C.; Mercer, E. H.

    1957-01-01

    1. The presumptive cortical cells of hair in the undifferentiated matrix of the bulb contain mitochondria, agranular vesicles, and many small dense R.N.P. particles, but no keratin, pigment granules, or endoplasmic reticulum. 2. In the mid-bulb region intercellular adhesion is limited to small localised areas. Intercellular gaps are common and the cell surfaces are irregularly convoluted. The melanocyte processes penetrate the cell gaps. The relation between their pigment-bearing tips and the involutions of the cell membranes suggests an active phagocytosis of the tips. 3. Fibrous keratin first appears in loose parallel strands of fine filaments (ca. 60 A diameter) in the mid-bulb. The filaments, the long mitochondria, and elongated nucleus are all parallel to the long axis of the cell and the axis of the follicle. 4. At the level of the constriction of the bulb and above, a dense amorphous substance appears between the fine filaments and apparently acts as adhesive cement. The bundles of filaments now form well defined fibrils. The packing of the filaments within the fibrils is in places hexagonal and elsewhere in the form of "whorls." 5. At higher levels further filaments and interfilamentous cement are added together and the whole cytoplasmic space becomes packed with fibrils which finally condense to massive blocks of keratin. The residual cellular material occupies the interstices. 6. The addition of the interfilamentous substance is regarded as an essential factor in keratinisation. Keratin is considered to be a complex made of fine filaments (α-filaments) embedded in an amorphous substance (γ-keratin) which has the higher cystine content. 7. The wide-angle fibre-type x-ray pattern is thought to be due to scattering by the fine α-filaments and some low angle lateral spacings to the filament-plus-cement structure. PMID:13438903

  12. Inhibition of β-catenin signalling in dermal fibroblasts enhances hair follicle regeneration during wound healing

    PubMed Central

    Gomez, Celine; Pisco, Angela Oliveira; Rawlins, Emma L.; Simons, Ben D.

    2016-01-01

    New hair follicles (HFs) do not form in adult mammalian skin unless epidermal Wnt signalling is activated genetically or within large wounds. To understand the postnatal loss of hair forming ability we monitored HF formation at small circular (2 mm) wound sites. At P2, new HFs formed in back skin, but HF formation was markedly decreased by P21. Neonatal tail also formed wound-associated HFs, albeit in smaller numbers. Postnatal loss of HF neogenesis did not correlate with wound closure rate but with a reduction in Lrig1-positive papillary fibroblasts in wounds. Comparative gene expression profiling of back and tail dermis at P1 and dorsal fibroblasts at P2 and P50 showed a correlation between loss of HF formation and decreased expression of genes associated with proliferation and Wnt/β-catenin activity. Between P2 and P50, fibroblast density declined throughout the dermis and clones of fibroblasts became more dispersed. This correlated with a decline in fibroblasts expressing a TOPGFP reporter of Wnt activation. Surprisingly, between P2 and P50 there was no difference in fibroblast proliferation at the wound site but Wnt signalling was highly upregulated in healing dermis of P21 compared with P2 mice. Postnatal β-catenin ablation in fibroblasts promoted HF regeneration in neonatal and adult mouse wounds, whereas β-catenin activation reduced HF regeneration in neonatal wounds. Our data support a model whereby postnatal loss of hair forming ability in wounds reflects elevated dermal Wnt/β-catenin activation in the wound bed, increasing the abundance of fibroblasts that are unable to induce HF formation. PMID:27287810

  13. Complex changes in the apoptotic and cell differentiation programs during initiation of the hair follicle response to chemotherapy.

    PubMed

    Sharova, Tatyana Y; Poterlowicz, Krzysztof; Botchkareva, Natalia V; Kondratiev, Nikita A; Aziz, Ahmar; Spiegel, Jeffrey H; Botchkarev, Vladimir A; Sharov, Andrey A

    2014-12-01

    Chemotherapy has severe side effects in normal rapidly proliferating organs, such as hair follicles, and causes massive apoptosis in hair matrix keratinocytes followed by hair loss. To define the molecular signature of hair follicle response to chemotherapy, human scalp hair follicles cultured ex vivo were treated with doxorubicin (DXR), and global microarray analysis was performed 3 hours after treatment. Microarray data revealed changes in expression of 504 genes in DXR-treated hair follicles versus controls. Among these genes, upregulations of several tumor necrosis factor family of apoptotic receptors (FAS, TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) receptors 1/2), as well as of a large number of keratin-associated protein genes, were seen after DXR treatment. Hair follicle apoptosis induced by DXR was significantly inhibited by either TRAIL-neutralizing antibody or caspase-8 inhibitor, thus suggesting a previously unreported role for TRAIL receptor signaling in mediating DXR-induced hair loss. These data demonstrate that the early phase of the hair follicle response to DXR includes upregulation of apoptosis-associated markers, as well as substantial reorganization of the terminal differentiation programs in hair follicle keratinocytes. These data provide an important platform for further studies toward the design of effective approaches for the management of chemotherapy-induced hair loss.

  14. Expression of retinoid nuclear receptor superfamily members in human hair follicles and its implication in hair growth.

    PubMed

    Billoni, N; Gautier, B; Mahé, Y F; Bernard, B A

    1997-09-01

    Since clinical evidence of hair loss and hair depigmentation following etretinate therapy has been reported, we decided to study the expression levels of several members of the retinoid nuclear receptor superfamily in dermal and epithelial compartments of the human hair follicle. Additionally, we evaluated the effects of several ligands for these receptors on human hair growth in culture in vitro. We observed that the cellular/ cytoplasmic retinoic acid (RA) binding protein-II and the retinoid-X-receptor-alpha were constantly and strongly expressed in both compartments at levels comparable to those of vitamin D receptor. In dermal papilla cells, by contrast with RAR beta which was always expressed, RAR alpha and RAR gamma were not constantly expressed. In dermal sheath fibroblasts, both RAR alpha, RAR beta and RAR gamma mRNAs were moderately expressed, while in the epithelial compartment, namely the plucked hair, we observed the expression of the same genes in the absence of RAR beta. We also observed that RAR agonists all-trans RA and CD367 inhibited the survival of human hair follicles in culture in vitro, while RXR agonist CD2425 stimulated hair growth and survival at levels comparable to those of 1 alpha,25-dihydroxyvitamin D3, suggesting that RXR agonists might stimulate hair growth in humans in vivo.

  15. A comparison of temperature profile depending on skin types for laser hair removal therapy.

    PubMed

    Kim, Tae-Hoon; Lee, Gwi-Won; Youn, Jong-In

    2014-11-01

    Although numerous lasers with different wavelengths are available for laser hair removal, their use in individuals with dark-pigmented skin remains a challenge. The present study aims to develop a numerical heat diffusion model considering skin types over various wavelengths. This numerical mode uses Pennes approximation to represent heat from metabolism, blood perfusion and an external heating source. The heat diffusion model is experimentally validated by using agar-based skin tissue phantoms. Diode lasers with four different wavelengths were used with two antithetical skin models. The pulse width and beam spot size were set to 200 ms and 1 cm(2), respectively. Temperature distribution along the hair structure and skin tissue was examined to determine both thermal confinement and heat transfer to the hair follicle. Experimental results are well matched with the numerical results. The results show that for the light skin model, thermal confinement is well achieved over various wavelengths, and treatment efficacy is expected to be better at a shorter wavelength. Otherwise, for the dark skin model, thermal confinement is poorly achieved as the wavelength decreases (<808 nm) and the temperature gap between the hair tip and the hair root is significantly large compared with the light skin model, which may lead to adverse effects. We believe that the developed numerical model will help to establish optimal laser parameters for different individuals during laser hair removal.

  16. Identification and localization of insulin-like growth factor-binding protein (IGFBP) messenger RNAs in human hair follicle dermal papilla.

    PubMed

    Batch, J A; Mercuri, F A; Werther, G A

    1996-03-01

    The role of the insulin-like growth factors (IGFs) in hair follicle biology has recently been recognized, although their actions, sites of production, and modulation by the insulin-like growth factor-binding proteins (IGFBPs) have not to date been defined. IGF-I is essential for normal hair growth and development, and may be important in regulation of the hair growth cycle. In many culture systems, IGF-I actions are modulated by the IGFBPs. Thus, if IGFBPs are produced in the human hair follicle, they may play a role in targeting IGF-I to its receptor or may modulate IGF-I action by interaction with matrix proteins. We have used in situ hybridization to localize messenger RNA for the six IGFBPs in anagen hair follicles. Anti-sense and sense RNA probes for the IGFBPs (IGFBP-1 to -6) were produced, and 5-micrometer sections of adult facial skin were probed. Messenger RNA for IGFBP-3, -4, and -5 were identified, with predominantly IGFBP-3 and -5 mRNA found in the dermal papilla, and to a lesser extent IGFBP-4 mRNA. IGFBP-4 mRNA was also found at the dermal papilla/epithelial matrix border. Messenger RNAs for both IGFBP-4 and -5 were also demonstrated in the dermal sheath surrounding the hair follicle. Messenger RNAs for IGFBP-1, -2, and -6 were not identified. These studies demonstrate specific localization of IGFBP mRNAs in hair follicles, suggesting that they each play specific roles in the local modulation of IGF action during the hair growth cycle.

  17. Tbx18 targets dermal condensates for labeling, isolation, and gene ablation during embryonic hair follicle formation.

    PubMed

    Grisanti, Laura; Clavel, Carlos; Cai, Xiaoqiang; Rezza, Amelie; Tsai, Su-Yi; Sennett, Rachel; Mumau, Melanie; Cai, Chen-Leng; Rendl, Michael

    2013-02-01

    How cell fate decisions of stem and progenitor cells are regulated by their microenvironment or niche is a central question in stem cell and regenerative biology. Although functional analysis of hair follicle epithelial stem cells by gene targeting is well established, the molecular and genetic characterization of the dermal counterpart during embryonic morphogenesis has been lacking because of the absence of cell type-specific drivers. Here, we report that T-box transcription factor Tbx18 specifically marks dermal papilla (DP) precursor cells during embryonic hair follicle morphogenesis. With Tbx18(LacZ), Tbx18(H2BGFP), and Tbx18(Cre) knock-in mouse models, we demonstrate LacZ and H2BGFP (nuclear green fluorescent protein) expression and Cre activity in dermal condensates of nascent first-wave hair follicles at E14.5. As Tbx18 expression becomes more widespread throughout the dermis at later developmental stages, we use tamoxifen-inducible Cre-expressing mice, Tbx18(MerCreMer), to exclusively target DP precursor cells and their progeny. Finally, we ablate Tbx18 in full knockout mice, but find no perturbations in hair follicle formation, suggesting that Tbx18 is dispensable for normal DP function. In summary, our study establishes Tbx18 as a genetic driver to target for the first time embryonic DP precursors for labeling, isolation, and gene ablation that will greatly enhance investigations into their molecular functions during hair follicle morphogenesis.

  18. Effects of a Closed Space Environment on Gene Expression in Hair Follicles of Astronauts in the International Space Station

    PubMed Central

    Terada, Masahiro; Seki, Masaya; Takahashi, Rika; Yamada, Shin; Higashibata, Akira; Majima, Hideyuki J.; Sudoh, Masamichi; Mukai, Chiaki; Ishioka, Noriaki

    2016-01-01

    Adaptation to the space environment can sometimes pose physiological problems to International Space Station (ISS) astronauts after their return to earth. Therefore, it is important to develop healthcare technologies for astronauts. In this study, we examined the feasibility of using hair follicles, a readily obtained sample, to assess gene expression changes in response to spaceflight adaptation. In order to investigate the gene expression changes in human hair follicles during spaceflight, hair follicles of 10 astronauts were analyzed by microarray and real time qPCR analyses. We found that spaceflight alters human hair follicle gene expression. The degree of changes in gene expression was found to vary among individuals. In some astronauts, genes related to hair growth such as FGF18, ANGPTL7 and COMP were upregulated during flight, suggesting that spaceflight inhibits cell proliferation in hair follicles. PMID:27029003

  19. Effects of a Closed Space Environment on Gene Expression in Hair Follicles of Astronauts in the International Space Station.

    PubMed

    Terada, Masahiro; Seki, Masaya; Takahashi, Rika; Yamada, Shin; Higashibata, Akira; Majima, Hideyuki J; Sudoh, Masamichi; Mukai, Chiaki; Ishioka, Noriaki

    2016-01-01

    Adaptation to the space environment can sometimes pose physiological problems to International Space Station (ISS) astronauts after their return to earth. Therefore, it is important to develop healthcare technologies for astronauts. In this study, we examined the feasibility of using hair follicles, a readily obtained sample, to assess gene expression changes in response to spaceflight adaptation. In order to investigate the gene expression changes in human hair follicles during spaceflight, hair follicles of 10 astronauts were analyzed by microarray and real time qPCR analyses. We found that spaceflight alters human hair follicle gene expression. The degree of changes in gene expression was found to vary among individuals. In some astronauts, genes related to hair growth such as FGF18, ANGPTL7 and COMP were upregulated during flight, suggesting that spaceflight inhibits cell proliferation in hair follicles.

  20. Dynamics of Lgr6+ Progenitor Cells in the Hair Follicle, Sebaceous Gland, and Interfollicular Epidermis

    PubMed Central

    Füllgrabe, Anja; Joost, Simon; Are, Alexandra; Jacob, Tina; Sivan, Unnikrishnan; Haegebarth, Andrea; Linnarsson, Sten; Simons, Benjamin D.; Clevers, Hans; Toftgård, Rune; Kasper, Maria

    2015-01-01

    Summary The dynamics and interactions between stem cell pools in the hair follicle (HF), sebaceous gland (SG), and interfollicular epidermis (IFE) of murine skin are still poorly understood. In this study, we used multicolor lineage tracing to mark Lgr6-expressing basal cells in the HF isthmus, SG, and IFE. We show that these Lgr6+ cells constitute long-term self-renewing populations within each compartment in adult skin. Quantitative analysis of clonal dynamics revealed that the Lgr6+ progenitor cells compete neutrally in the IFE, isthmus, and SG, indicating population asymmetry as the underlying mode of tissue renewal. Transcriptional profiling of Lgr6+ and Lgr6− cells did not reveal a distinct Lgr6-associated gene expression signature, raising the question of whether Lgr6 expression requires extrinsic niche signals. Our results elucidate the interrelation and behavior of Lgr6+ populations in the IFE, HF, and SG and suggest population asymmetry as a common mechanism for homeostasis in several epithelial skin compartments. PMID:26607954

  1. KCNQ Potassium Channels Modulate Sensitivity of Skin Down-hair (D-hair) Mechanoreceptors.

    PubMed

    Schütze, Sebastian; Orozco, Ian J; Jentsch, Thomas J

    2016-03-11

    M-current-mediating KCNQ (Kv7) channels play an important role in regulating the excitability of neuronal cells, as highlighted by mutations in Kcnq2 and Kcnq3 that underlie certain forms of epilepsy. In addition to their expression in brain, KCNQ2 and -3 are also found in the somatosensory system. We have now detected both KCNQ2 and KCNQ3 in a subset of dorsal root ganglia neurons that correspond to D-hair Aδ-fibers and demonstrate KCNQ3 expression in peripheral nerve endings of cutaneous D-hair follicles. Electrophysiological recordings from single D-hair afferents from Kcnq3(-/-) mice showed increased firing frequencies in response to mechanical ramp-and-hold stimuli. This effect was particularly pronounced at slow indentation velocities. Additional reduction of KCNQ2 expression further increased D-hair sensitivity. Together with previous work on the specific role of KCNQ4 in rapidly adapting skin mechanoreceptors, our results show that different KCNQ isoforms are specifically expressed in particular subsets of mechanosensory neurons and modulate their sensitivity directly in sensory nerve endings.

  2. Noninvasive method for assessing the human circadian clock using hair follicle cells

    PubMed Central

    Akashi, Makoto; Soma, Haruhiko; Yamamoto, Takuro; Tsugitomi, Asuka; Yamashita, Shiko; Yamamoto, Takuya; Nishida, Eisuke; Yasuda, Akio; Liao, James K.; Node, Koichi

    2010-01-01

    A thorough understanding of the circadian clock requires qualitative evaluation of circadian clock gene expression. Thus far, no simple and effective method for detecting human clock gene expression has become available. This limitation has greatly hampered our understanding of human circadian rhythm. Here we report a convenient, reliable, and less invasive method for detecting human clock gene expression using biopsy samples of hair follicle cells from the head or chin. We show that the circadian phase of clock gene expression in hair follicle cells accurately reflects that of individual behavioral rhythms, demonstrating that this strategy is appropriate for evaluating the human peripheral circadian clock. Furthermore, using this method, we indicate that rotating shift workers suffer from a serious time lag between circadian gene expression rhythms and lifestyle. Qualitative evaluation of clock gene expression in hair follicle cells, therefore, may be an effective approach for studying the human circadian clock in the clinical setting. PMID:20798039

  3. Topical formulations containing finasteride. Part II: determination of finasteride penetration into hair follicles using the differential stripping technique.

    PubMed

    Tampucci, Silvia; Burgalassi, Susi; Chetoni, Patrizia; Lenzi, Carla; Pirone, Andrea; Mailland, Federico; Caserini, Maurizio; Monti, Daniela

    2014-08-01

    The differential stripping technique consists of a tape-stripping phase followed by a cyanoacrylate biopsy. This technique not only allows the quantification of drug retained in the stratum corneum (SC) and in the hair follicles but also differentiates transepidermal from transfollicular penetration. Our study aimed at both validating the differential stripping procedure on hairless rat skin and assessing the role of the hair follicle in the cutaneous penetration of finasteride (FNS) after application of two experimental formulations for 6 or 24 h: P-08-016, a hydroxypropyl chitosan (HPCH)-based formulation and P-10-008, an anhydrous formulation devoid of HPCH. Microscopic and histological evaluation showed that after 15 tape strips both the SC and the viable epidermis were completely removed. A subsequent cyanoacrylate skin surface biopsy led to the removal of the infundibula content. The largest amounts of FNS were found in the epidermis and in the appendages after application of P-08-016, regardless of the time from application. In contrast, smaller and statistically significant amounts of FNS were recovered with P-10-008 6 h after application, compared with that at 24 h. In conclusion, the differential stripping technique allowed determination of the amount of FNS localized in different skin districts, focusing particularly on the follicular contribution.

  4. Targeted deletion of Crif1 in mouse epidermis impairs skin homeostasis and hair morphogenesis

    PubMed Central

    Shin, Jung-Min; Choi, Dae-Kyoung; Sohn, Kyung-Cheol; Kim, Ji-Young; Im, Myung; Lee, Young; Seo, Young-Joon; Shong, Minho; Lee, Jeung-Hoon; Kim, Chang Deok

    2017-01-01

    The epidermis, which consists mainly of keratinocytes, acts as a physical barrier to infections by regulating keratinocyte proliferation and differentiation. Hair follicles undergo continuous cycling to produce new one. Therefore, optimum supply of energy from the mitochondria is essential for maintaining skin homeostasis and hair growth. CRIF1 is a mitochondrial protein that regulates mitoribosome-mediated synthesis and insertion of mitochondrial oxidative phosphorylation polypeptides into the mitochondrial membrane in mammals. Recent studies reveal that conditional knockout (cKO) of Crif1 in specific tissues of mice induced mitochondrial dysfunction. To determine whether the mitochondrial function of keratinocytes affects skin homeostasis and hair morphogenesis, we generated epidermis-specific Crif1 cKO mice. Deletion of Crif1 in epidermis resulted in impaired mitochondrial function and Crif1 cKO mice died within a week. Keratinocyte proliferation and differentiation were markedly inhibited in Crif1 cKO mice. Furthermore, hair follicle morphogenesis of Crif1 cKO mice was disrupted by down-regulation of Wnt/β-catenin signaling. These results demonstrate that mitochondrial function in keratinocytes is essential for maintaining epidermal homeostasis and hair follicle morphogenesis. PMID:28317864

  5. Mitochondrial aerobic respiration is activated during hair follicle stem cell differentiation, and its dysfunction retards hair regeneration

    PubMed Central

    Tang, Yan; Luo, Binping; Deng, Zhili; Wang, Ben; Liu, Fangfen; Li, Jinmao; Shi, Wei; Xie, Hongfu; Hu, Xingwang

    2016-01-01

    Background. Emerging research revealed the essential role of mitochondria in regulating stem/progenitor cell differentiation of neural progenitor cells, mesenchymal stem cells and other stem cells through reactive oxygen species (ROS), Notch or other signaling pathway. Inhibition of mitochondrial protein synthesis results in hair loss upon injury. However, alteration of mitochondrial morphology and metabolic function during hair follicle stem cells (HFSCs) differentiation and how they affect hair regeneration has not been elaborated upon. Methods. We compared the difference in mitochondrial morphology and activity between telogen bulge cells and anagen matrix cells. Expression levels of mitochondrial ROS and superoxide dismutase 2 (SOD2) were measured to evaluate redox balance. In addition, the level of pyruvate dehydrogenase kinase (PDK) and pyruvate dehydrogenase (PDH) were estimated to present the change in energetic metabolism during differentiation. To explore the effect of the mitochondrial metabolism on regulating hair regeneration, hair growth was observed after application of a mitochondrial respiratory inhibitor upon hair plucking. Results. During HFSCs differentiation, mitochondria became elongated with more abundant organized cristae and showed higher activity in differentiated cells. SOD2 was enhanced for redox balance with relatively stable ROS levels in differentiated cells. PDK increased in HFSCs while differentiated cells showed enhanced PDH, indicating that respiration switched from glycolysis to oxidative phosphorylation during differentiation. Inhibiting mitochondrial respiration in differentiated hair follicle cells upon hair plucking repressed hair regeneration in vivo. Conclusions. Upon HFSCs differentiation, mitochondria are elongated with more abundant cristae and show higher activity, accompanying with activated aerobic respiration in differentiated cells for higher energy supply. Also, dysfunction of mitochondrial respiration delays hair

  6. The dog mite, Demodex canis: prevalence, fungal co-infection, reactions to light, and hair follicle apoptosis.

    PubMed

    Tsai, Yu-Jen; Chung, Wen-Cheng; Wang, Lian-Chen; Ju, Yu-Ten; Hong, Chin-Lin; Tsai, Yu-Yang; Li, Yi-Hung; Wu, Ying-Ling

    2011-01-01

    Infection rate, reaction to light, and hair follicle apoptosis are examined in the dogmite, Demodex canis Leydig (Prostigmata: Demodicidae), in dogs from the northern area of Taiwan. An analysis of relevant samples revealed 7.2% (73/1013) prevalence of D. canis infection. Infection during the investigation peaked each winter, with an average prevalence of 12.5% (32/255). The infection rates significantly varied in accordance with month, sex, age, and breed (p < 0.05). Most of the lesions were discovered on the backs of the infected animals, where the infection rate was 52.1% (38/73) (P < 0.05). The epidemiologic analysis of infection based on landscape area factor, found that employing a map-overlapping method showed a higher infection rate in the eastern distribution of Taiwan's northern area than other areas. Isolation tests for Microsporum canis Bodin (Onygenales: Arthrodermataceae) and Trichophyton mentagrophyte Robin (Blanchard) on the D. canis infected dogs revealed prevalence rates of 4.4% (2/45) and 2.2% (1/45), respectively. Observations demonstrated that D. canis slowly moved from a light area to a dark area. Skin samples were examined for cellular apoptosis by activated caspase3 immunohistochemical staining. Cells that surrounded the infected hair follicles were activated caspase3-positive, revealing cell apoptosis in infected follicles via the activation of caspase3.

  7. Squarticles as a lipid nanocarrier for delivering diphencyprone and minoxidil to hair follicles and human dermal papilla cells.

    PubMed

    Aljuffali, Ibrahim A; Sung, Calvin T; Shen, Feng-Ming; Huang, Chi-Ting; Fang, Jia-You

    2014-01-01

    Delivery of diphencyprone (DPCP) and minoxidil to hair follicles and related cells is important in the treatment of alopecia. Here we report the development of "squarticles," nanoparticles formed from sebum-derived lipids such as squalene and fatty esters, for use in achieving targeted drug delivery to the follicles. Two different nanosystems, nanostructured lipid carriers (NLC) and nanoemulsions (NE), were prepared. The physicochemical properties of squarticles, including size, zeta potential, drug encapsulation efficiency, and drug release, were examined. Squarticles were compared to a free control solution with respect to skin absorption, follicular accumulation, and dermal papilla cell targeting. The particle size of the NLC type was 177 nm; that of the NE type was 194 nm. Approximately 80% of DPCP and 60% of minoxidil were entrapped into squarticles. An improved drug deposition in the skin was observed in the in vitro absorption test. Compared to the free control, the squarticles reduced minoxidil penetration through the skin. This may indicate a minimized absorption into systemic circulation. Follicular uptake by squarticles was 2- and 7-fold higher for DPCP and minoxidil respectively compared to the free control. Fluorescence and confocal images of the skin confirmed a great accumulation of squarticles in the follicles and the deeper skin strata. Vascular endothelial growth factor expression in dermal papilla cells was significantly upregulated after the loading of minoxidil into the squarticles. In vitro papilla cell viability and in vivo skin irritancy tests in nude mice suggested a good tolerability of squarticles to skin. Squarticles provide a promising nanocarrier for topical delivery of DPCP and minoxidil.

  8. Characterization of rat hair follicle stem cells selected by vario magnetic activated cell sorting system.

    PubMed

    Huang, Enyi; Lian, Xiaohua; Chen, Wei; Yang, Tian; Yang, Li

    2009-10-30

    Hair follicle stem cells (HfSCs) play crucial roles in hair follicle morphogenesis and hair cycling. These stem cells are self-renewable and have the multi-lineage potential to generate epidermis, sebaceous glands, and hair follicle. The separation and identification of hair follicle stem cells are important for further research in stem cell biology. In this study, we report on the successful enrichment of rat hair follicle stem cells through vario magnetic activated cell sorting (Vario MACS) and the biological characteristics of the stem cells. We chose the HfSCs positive surface markers CD34, alpha 6-integrin and the negative marker CD71 to design four isolation strategies: positive selection with single marker of CD34, positive selection with single marker of alpha 6-integrin, CD71 depletion followed by CD34 positive selection, and CD71 depletion followed by alpha 6-integrin positive selection. The results of flow cytometry analysis showed that all four strategies had ideal effects. Specifically, we conducted a series of researches on HfSCs characterized by their high level of CD34, termed CD34(bri) cells, and low to undetectable expression of CD34, termed CD34(dim) cells. CD34(bri) cells had greater proliferative potential and higher colony-forming ability than CD34(dim) cells. Furthermore, CD34(bri) cells had some typical characteristics as progenitor cells, such as large nucleus, obvious nucleolus, large nuclear:cytoplasmic ratio and few cytoplasmic organelles. Our findings clearly demonstrated that HfSCs with high purity and viability could be successfully enriched with Vario MACS.

  9. Hair follicles' transit-amplifying cells govern concurrent dermal adipocyte production through Sonic Hedgehog.

    PubMed

    Zhang, Bing; Tsai, Pai-Chi; Gonzalez-Celeiro, Meryem; Chung, Oliver; Boumard, Benjamin; Perdigoto, Carolina N; Ezhkova, Elena; Hsu, Ya-Chieh

    2016-10-15

    Growth and regeneration of one tissue within an organ compels accommodative changes in the surrounding tissues. However, the molecular nature and operating logic governing these concurrent changes remain poorly defined. The dermal adipose layer expands concomitantly with hair follicle downgrowth, providing a paradigm for studying coordinated changes of surrounding lineages with a regenerating tissue. Here, we discover that hair follicle transit-amplifying cells (HF-TACs) play an essential role in orchestrating dermal adipogenesis through secreting Sonic Hedgehog (SHH). Depletion of Shh from HF-TACs abrogates both dermal adipogenesis and hair follicle growth. Using cell type-specific deletion of Smo, a gene required in SHH-receiving cells, we found that SHH does not act on hair follicles, adipocytes, endothelial cells, and hematopoietic cells for adipogenesis. Instead, SHH acts directly on adipocyte precursors, promoting their proliferation and their expression of a key adipogenic gene, peroxisome proliferator-activated receptor γ (Pparg), to induce dermal adipogenesis. Our study therefore uncovers a critical role for TACs in orchestrating the generation of both their own progeny and a neighboring lineage to achieve concomitant tissue production across lineages.

  10. Hair follicle units promote re-epithelialization in chronic cutaneous wounds: A clinical case series study.

    PubMed

    Liu, Jia-Qi; Zhao, Kong-Bo; Feng, Zi-Hao; Qi, Fa-Zhi

    2015-07-01

    Chronic cutaneous wounds are one of the most unfavorable pathophysiological processes in routine practice. However, developments in hair follicle unit therapy may aid the treatment of these wounds. The aim of the present study was to investigate the function of hair follicle units in chronic cutaneous wound re-epithelialization and to develop an effective protocol for wound treatment. A total of 14 patients, of which nine were male and five were female, with a mean age of 60.71 years (range, 19-76 years) and a mean wound area of 74.14 cm(2), were treated in the study. The hair follicle units were dissected from a scalp graft and transplanted into the chronic cutaneous wound bed, after which clinical evaluation was performed. Images of the recipient site were captured at 0, 1, 2, 3, 4, 5, 8 and 14 weeks following transplantation. In addition, histological examinations were conducted postoperatively at week 16. Total wound re-epithelialization was observed in all the patients. Histological analysis revealed that the epidermis and papillary dermis were present in the wound area. Adnexal structures and the reticular dermis were also observed. Therefore, the present study demonstrated the ability of hair follicle units to promote chronic cutaneous wound healing.

  11. Outer root sheath keratinization in anagen and catagen of the mammalian hair follicle. A seventh distinct type of keratinization in the hair follicle: trichilemmal keratinization.

    PubMed

    Pinkus, H; Iwasaki, T; Mishima, Y

    1981-08-01

    Trichilemmal keratinization, first described in Maurer in 1895 and rediscovered by Holmes (1968) and Pinkus (1968) converts the stratified epithelium of the outer root sheath into anuclear keratin without an intervening keratohyalin layer. It is a distinct seventh type of keratinization in the hair follicle, not derived from the hair matrix. It occurs wherever outer root sheath is not apposed to inner root sheath, in anagen in the zone of sloughing just below the opening of the sebaceous duct, in catagen in the trichilemmal sac surrounding the lower end of the dying hair shaft where it forms the club of the telogen hair. Electron microscopic study of the thick hairs of dogs (but not the tiny hairs of rodents) reveals intricate infoldings of non-keratinized and keratinized cells. It also shows unique ladder-like membrane coating granules in anagen, which are strongly acid phosphatase-positive and are suggested to be the source of enzyme involved with disintegration of the inner root sheath.

  12. Skin pigmentation and texture changes after hair removal with the normal-mode ruby laser.

    PubMed

    Haedersdal, M; Egekvist, H; Efsen, J; Bjerring, P

    1999-11-01

    Promising clinical results have been obtained with the normal mode ruby laser for removal of unwanted hair. Melanin within the hair follicles is thought to act as target for the ruby laser pulses, whereas epidermal melanin is thought to be a competitive chromophore, responsible for potential side effects. This study aimed (i) to objectify postoperative changes in skin pigmentation and texture and (ii) to evaluate the importance of variations in preoperative skin pigmentation for the development of side effects 12 weeks after 1 treatment with the normal-mode ruby laser. A total of 17 volunteers (skin types I-IV) were laser-treated in the hairy pubic region (n = 51 test areas). A shaved test area served as control. Skin reflectance spectroscopical measurements, 3-dimensional surface contour analysis and ultrasonography objectified postoperative changes in skin pigmentation and texture. Blinded clinical assessments revealed postoperative hyperpigmentation (2% of test areas) and hypopigmentation (10%), whereas no textural changes were seen. Reflectance spectroscopically-determined pigmentary changes depended on the degree of preoperative skin pigmentation, fairly pigmented skin types experiencing subclinical hyperpigmentation and darkly pigmented skin types experiencing subclinical hypopigmentation. Three-dimensional surface profilometry documented similar pre- and postoperative surface contour parameters, indicating that the skin surface texture is preserved after laser exposure. Ultrasonography revealed similar skin thicknesses in laser-exposed and untreated control areas. It is concluded that normal-mode ruby laser treatment is safe for hair removal in skin types I-IV.

  13. Cxcr4 is transiently expressed in both epithelial and mesenchymal compartments of nascent hair follicles but is not required for follicle formation.

    PubMed

    Sennett, Rachel; Rezza, Amélie; Dauber, Katherine L; Clavel, Carlos; Rendl, Michael

    2014-10-01

    Hair follicle (HF) morphogenesis relies on the coordinated exchange of signals between mesenchymal and epithelial compartments of embryonic skin. Chemokine receptor Cxcr4 expression was recently identified in dermal condensates (DCs) of nascent HFs, but its role in promoting HF morphogenesis remains unknown. Our analyses confirmed Cxcr4 expression in condensate cells, and additionally revealed transient Cxcr4 expression in incipient epithelial hair placodes. Placodal Cxcr4 appeared prior to detection in DCs, representing a switch of expression between epithelial and mesenchymal compartments. To explore the functional role of this receptor in both compartments for early HF formation, we conditionally ablated Cxcr4 with condensate-targeting Tbx18(cre) knock-in and epidermis-targeting Krt14-cre transgenic mice. Conditional knockouts for both crosses were viable throughout embryogenesis and into adulthood. Morphological and biochemical marker analyses revealed comparable numbers of HFs forming in knockout embryos compared to wild-type littermate controls in both cases, suggesting that neither dermal nor epithelial Cxcr4 expression is required for early HF morphogenesis. We conclude that Cxcr4 expression and chemokine signaling through this receptor in embryonic mouse skin is dispensable for HF formation.

  14. Determination of the cuticula thickness of human and porcine hairs and their potential influence on the penetration of nanoparticles into the hair follicles

    NASA Astrophysics Data System (ADS)

    Lademann, Juergen; Patzelt, Alexa; Richter, Heike; Antoniou, Christina; Sterry, Wolfram; Knorr, Fanny

    2009-03-01

    An efficient penetration and long-term storage of topically applied substances is important for drug delivery in medical treatment and cosmetics. It has recently become apparent that the hair follicles represent an efficient and long-term reservoir for topically applied substances. It was found that particles sized 300-600 nm penetrate more efficiently into the hair follicles than smaller or larger particles. In the present paper, the hair surface structure of human and porcine hairs was analyzed by electron microscopy. It could be observed that the thickness of the cuticula corresponds to the optimal size of the nanoparticles for penetration into the hair follicles. Additionally, it could be demonstrated that the cuticula of human vellus and terminal hairs were of similar thickness (approx. 530 nm), while the thickness of the cuticula obtained from porcine ear bristles were slightly thinner (approx. 320 nm).

  15. Hair follicle morphogenesis and epidermal homeostasis in we/we wal/wal mice with postnatal alopecia.

    PubMed

    Rippa, Alexandra; Terskikh, Vasily; Nesterova, Anastasia; Vasiliev, Andrey; Vorotelyak, Ekaterina

    2015-05-01

    Mice with skin and hair follicle (HF) defects are common models of human skin disorders. A mutant strain with the we/we wal/wal genotype develops alopecia. We found the hair shaft structure in the pelage of mutant mice to have significant defects. Although these mice lose their hair at 21 days, a label-retaining cell population persists in HFs until at least day 54. Depilation-induced anagen was accomplished in we/we wal/wal mutants but the resulting hair shafts were short and extremely deformed. Serious abnormalities in epidermis stratification and HF morphogenesis exist in we/we wal/wal homozygous E18.5 embryos. There were significantly fewer HF primordia in this mutant compared with wild type. We discovered specific structures, identified as invalid placodes, positive for ectodysplasin A1 receptor, nuclear β-catenin, and LEF1, which failed to invaginate, produced a double basal-like layer of epidermal cells, and lacked cylindrical keratinocytes. Specification of dermal papillae (DP) was impaired, and the papillary dermis expressed alkaline phosphatase and LEF1. We also detected DP-like groups of intensively stained cells in the absence of visible signs of folliculogenesis in the epidermis. We showed differentiation disturbances in the mutant embryonic E18.5 epidermis and HFs: The cornified layer was absent, the width of the spinous layer was reduced, and HFs lacked LEF1-positive precortex cells. In this study, we used a very interesting and useful mouse model of alopecia. The presence of symptoms of skin disorders in we/we wal/wal murine embryos correlates with the postnatal skin phenotype. This correlation may help to evaluate reasons of alopecia.

  16. Development of a Model for Chemotherapy-Induced Alopecia: Profiling of Histological Changes in Human Hair Follicles after Chemotherapy.

    PubMed

    Yoon, Ji-Seon; Choi, Mira; Shin, Chang Yup; Paik, Seung Hwan; Kim, Kyu Han; Kwon, Ohsang

    2016-03-01

    Optimized research models are required to further understand the pathogenesis and prophylaxis of chemotherapy-induced alopecia. Our aim was to develop a mouse model for chemotherapy-induced alopecia by follicular unit transplantation of human hair follicles onto immunodeficient mice. Twenty-two weeks after transplantation, a single dose of cyclophosphamide (Cph) was administered to mice in the Cph100 (100 mg/kg) and Cph150 (150 mg/kg) groups. On day 6, hair follicles showed dystrophic changes, with swollen dermal papilla and ectopic melanin clumping in the hair bulb. In addition, upregulated expression of apoptotic regulators [P53, Fas/Fas-ligand, tumor necrosis factor-related apoptosis-inducing ligand/tumor necrosis factor-related apoptosis-inducing ligand receptor (TRAIL/TRAIL receptor), and Bax], increased apoptotic matrix keratinocytes, downregulated Ki67 expression, and decreased melanogenic protein in the hair bulb were noted in both groups. After 12 treatment days, hair follicles in Cph100 mice appeared to diminish dystrophic changes. In contrast, hair follicles of Cph150 mice prematurely entered a dystrophic catagen phase after 9 treatment days, and immunofluorescence staining for Ki67 and melanogenic protein expressions was barely visible. Two hair follicle damage response pathways were observed in this model, namely dystrophic anagen (Cph100) and catagen (Cph150) pathways. Our model might be useful for further understanding the impact of chemotherapy on human hair follicles.

  17. A review of adipocyte lineage cells and dermal papilla cells in hair follicle regeneration

    PubMed Central

    Zhang, Peipei; Kling, Russell E; Ravuri, Sudheer K; Kokai, Lauren E; Rubin, J Peter; Chai, Jia-ke

    2014-01-01

    Alopecia is an exceedingly prevalent problem effecting men and women of all ages. The standard of care for alopecia involves either transplanting existing hair follicles to bald areas or attempting to stimulate existing follicles with topical and/or oral medication. Yet, these treatment options are fraught with problems of cost, side effects, and, most importantly, inadequate long-term hair coverage. Innovative cell-based therapies have focused on the dermal papilla cell as a way to grow new hair in previously bald areas. However, despite this attention, many obstacles exist, including retention of dermal papilla inducing ability and maintenance of dermal papilla productivity after several passages of culture. The use of adipocyte lineage cells, including adipose-derived stem cells, has shown promise as a cell-based solution to regulate hair regeneration and may help in maintaining or increasing dermal papilla cells inducing hair ability. In this review, we highlight recent advances in the understanding of the cellular contribution and regulation of dermal papilla cells and summarize adipocyte lineage cells in hair regeneration. PMID:25383178

  18. Induction of osteoblastic differentiation of neural crest-derived stem cells from hair follicles.

    PubMed

    Urano-Morisawa, Eri; Takami, Masamichi; Suzawa, Tetsuo; Matsumoto, Akifumi; Osumi, Noriko; Baba, Kazuyoshi; Kamijo, Ryutaro

    2017-01-01

    The neural crest (NC) arises near the neural tube during embryo development. NC cells migrate throughout the embryo and have potential to differentiate into multiple cell types, such as peripheral nerves, glial, cardiac smooth muscle, endocrine, and pigment cells, and craniofacial bone. In the present study, we induced osteoblast-like cells using whisker follicles obtained from the NC of mice. Hair follicle cells derived from the NC labeled with enhanced green fluorescent protein (EGFP) were collected from protein zero-Cre/floxed-EGFP double transgenic mice and cultured, then treated and cultured in stem cell growth medium. After growth for 14 days, results of flow cytometry analysis showed that 95% of the EGFP-positive (EGFP+) hair follicle cells derived from the NC had proliferated and 76.2% of those expressed mesenchymal stem cells markers, such as platelet-derived growth factor α and stem cell antigen-1, and also showed constitutive expression of Runx2 mRNA. Cells stimulated with bone morphogenetic protein-2 expressed osteocalcin, osterix, and alkaline phosphatase mRNA, resulting in production of mineralized matrices, which were detected by von Kossa and alizarin red staining. Moreover, EGFP+ hair follicle cells consistently expressed macrophage colony-stimulating factor and osteoprotegerin (OPG). Addition of 1α,25-dihydroxyvitamin D3 [1,25(OH)2D3] (10-8 M) to the cultures suppressed OPG expression and induced RANKL production in the cells. Furthermore, multinucleated osteoclasts appeared within 6 days after starting co-cultures of bone marrow cells with EGFP+ cells in the presence of 1,25(OH)2D3 and PGE2. These results suggest that NC-derived hair follicle cells possess a capacity for osteoblastic differentiation and may be useful for developing new bone regenerative medicine therapies.

  19. Targeted disruption of the protein kinase SGK3/CISK impairs postnatal hair follicle development.

    PubMed

    McCormick, James A; Feng, Yuxi; Dawson, Kevin; Behne, Martin J; Yu, Benjamin; Wang, Jian; Wyatt, Amanda W; Henke, Guido; Grahammer, Florian; Mauro, Theodora M; Lang, Florian; Pearce, David

    2004-09-01

    Members of the serum- and glucocorticoid-regulated kinase (SGK) family are important mediators of growth factor and hormone signaling that, like their close relatives in the Akt family, are regulated by lipid products of phosphatidylinositol-3-kinase. SGK3 has been implicated in the control of cell survival and regulation of ion channel activity in cultured cells. To begin to dissect the in vivo functions of SGK3, we generated and characterized Sgk3 null mice. These mice are viable and fertile, and in contrast to mice lacking SGK1 or Akt2, respectively, display normal sodium handling and glucose tolerance. However, although normal at birth, by postpartum day 4 they have begun to display an unexpected defect in hair follicle morphogenesis. The abnormality in hair follicle development is preceded by a defect in proliferation and nuclear accumulation of beta-catenin in hair bulb keratinocytes. Furthermore, in cultured keratinocytes, heterologous expression of SGK3 potently modulates activation of beta-catenin/Lef-1-mediated gene transcription. These data establish a role for SGK3 in normal postnatal hair follicle development, possibly involving effects on beta-catenin/Lef-1-mediated gene transcription.

  20. Genetics of hair and skin color.

    PubMed

    Rees, Jonathan L

    2003-01-01

    Differences in skin and hair color are principally genetically determined and are due to variation in the amount, type, and packaging of melanin polymers produced by melanocytes secreted into keratinocytes. Pigmentary phenotype is genetically complex and at a physiological level complicated. Genes determining a number of rare Mendelian disorders of pigmentation such as albinism have been identified, but only one gene, the melanocortin 1 receptor (MCR1), has so far been identified to explain variation in the normal population such as that leading to red hair, freckling, and sun-sensitivity. Genotype-phenotype relations of the MC1R are reviewed, as well as methods to improve the phenotypic assessment of human pigmentary status. It is argued that given advances in model systems, increases in technical facility, and the lower cost of genotype assessment, the lack of standardized phenotype assessment is now a major limit on advance.

  1. WNT and DKK Determine Hair Follicle Spacing Through a Reaction-Diffusion Mechanism

    NASA Astrophysics Data System (ADS)

    Sick, Stefanie; Reinker, Stefan; Timmer, Jens; Schlake, Thomas

    2006-12-01

    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.

  2. Malignant hair follicle tumors of the periorbital region: A review of literature and suggestion of a management guideline.

    PubMed

    Sia, Paul Ikgan; Figueira, Edwin; Allende, Alexandra; Selva, Dinesh

    2016-06-01

    Malignant hair follicle tumors are rare skin adnexal malignancies that have a predilection for the head and neck region. They can be categorized into a number of different subtypes. Histologically, they are distinct from their benign counterpart. To the best of our knowledge, there is no extensive review of these malignancies, especially in the periorbital region. We aim to provide a literature review and a guideline for management of these malignant tumors in the periorbital region. Database from Medline, PubMed, Embase, and Google Scholar were consulted. A total of 16 cases from the literature on hair follicle malignancies in the periorbital region were included in this review. The clinical presentations, diagnostic patterns, investigations used, and best management approach of these tumors are discussed. The American Joint Committee on Cancer (AJCC) 7(th) edition carcinoma of the eyelid staging system was used to describe their behaviors. We recommend wide excision surgery and a close follow-up for these tumors. Tumors presenting with a late stage require work-up for distant metastasis and consideration for exenteration procedures. The role of radiotherapy and chemotherapy in this context is still uncertain.

  3. PDGF signalling in the dermis and in dermal condensates is dispensable for hair follicle induction and formation.

    PubMed

    Rezza, Amélie; Sennett, Rachel; Tanguy, Manon; Clavel, Carlos; Rendl, Michael

    2015-06-01

    Embryonic hair follicle (HF) induction and formation is dependent on signalling crosstalk between the dermis and specialized dermal condensates on the mesenchymal side and epidermal cells and incipient placodes on the epithelial side, but the precise nature and succession of signals remain unclear. Platelet-derived growth factor (PDGF) signalling is involved in the development of several organs and the maintenance of adult tissues, including HF regeneration in the hair cycle. As both PDGF receptors, PDGFRα and PDGFRβ, are expressed in embryonic dermis and dermal condensates, we explored in this study the role of PDGF signalling in HF induction and formation in the developing skin mesenchyme. We conditionally ablated both PDGF receptors with Tbx18(Cre) in early dermal condensates before follicle formation, and with Prx1-Cre broadly in the ventral dermis prior to HF induction. In both PDGFR double mutants, HF induction and formation ensued normally, and the pattern of HF formation and HF numbers were unaffected. These data demonstrate that mesenchymal PDGF signalling, either in the specialized niche or broadly in the dermis, is dispensable for HF induction and formation.

  4. The targeted overexpression of a Claudin mutant in the epidermis of transgenic mice elicits striking epidermal and hair follicle abnormalities.

    PubMed

    Troy, Tammy-Claire; Turksen, Kursad

    2007-06-01

    Skin is one of the largest organs of the body, and is formed during development through a highly orchestrated process involving mesenchymal-epithelial interactions, cell commitment, and terminal differentiation. It protects against microorganism invasion and UV irradiation, inhibits water loss, regulates body temperature, and is an important part of the immune system. Using transgenic mouse technology, we have demonstrated that Claudin (Cldn)-containing tight junctions (TJs) are intricately involved in cell signaling during epidermal differentiation and that an epidermal suprabasal overexpression of Cldn6 results in a perturbed epidermal terminal differentiation program with distinct phenotypic abnormalities. To delineate the role of the Cldn cytoplasmic tail domain in epidermal differentiation, we engineered transgenic mice targeting the overexpression of a Cldn6 cytoplasmic tail-truncation mutant in the epidermis. Transgenic mice were characterized by a lethal barrier dysfunction in addition to the existence of hyperproliferative squamous invaginations/cysts replacing hair follicles. Immunohistochemical analysis revealed an epidermal cytoplasmic accumulation of Cldn6, Cldn11, Cldn12, and Cldn18, downregulation of Cldn1 and aberrant expression of various classical markers of epidermal differentiation; namely the basal keratins as well as K1, involucrin, loricrin, and filaggrin. Collectively these studies suggest an important role for Cldns in epidermal/hair follicle differentiation programs likely involving cross talk to signaling pathways (e.g., Notch) directing cell fate selection and differentiation.

  5. A Conditioned Medium of Umbilical Cord Mesenchymal Stem Cells Overexpressing Wnt7a Promotes Wound Repair and Regeneration of Hair Follicles in Mice

    PubMed Central

    Dong, Liang; Hao, Haojie; Liu, Jiejie; Ti, Dongdong; Tong, Chuan; Hou, Qian; Li, Meirong; Zheng, Jingxi; Liu, Gang

    2017-01-01

    Mesenchymal stem cells (MSCs) can affect the microenvironment of a wound and thereby accelerate wound healing. Wnt proteins act as key mediators of skin development and participate in the formation of skin appendages such as hair. The mechanisms of action of MSCs and Wnt proteins on skin wounds are largely unknown. Here, we prepared a Wnt7a-containing conditioned medium (Wnt-CM) from the supernatant of cultured human umbilical cord-MSCs (UC-MSCs) overexpressing Wnt7a in order to examine the effects of this CM on cutaneous healing. Our results revealed that Wnt-CM can accelerate wound closure and induce regeneration of hair follicles. Meanwhile, Wnt-CM enhanced expression of extracellular matrix (ECM) components and cell migration of fibroblasts but inhibited the migratory ability and expression of K6 and K16 in keratinocytes by enhancing expression of c-Myc. However, we found that the CM of fibroblasts treated with Wnt-CM (HFWnt-CM-CM) can also promote wound repair and keratinocyte migration; but there was no increase in the number of hair follicles of regeneration. These data indicate that Wnt7a and UC-MSCs have synergistic effects: they can accelerate wound repair and induce hair regeneration via cellular communication in the wound microenvironment. Thus, this study opens up new avenues of research on the mechanisms underlying wound repair. PMID:28337222

  6. The morphology of hair follicle afferent fibre collaterals in the spinal cord of the cat.

    PubMed

    Brown, A G; Rose, P K; Snow, P J

    1977-11-01

    1. The enzyme horseradish peroxidase (HRP) was injected into single axons that innervated hair follicle receptors to study the morphology of their collaterals in the dorsal horn of the cord. The axons were impaled near the dorsal root entrance zone in the lumbosacral spinal cord of anaesthetized cats and HRP injected by passing current through the intra-axonal micro-electrode. The morphology was revealed by subsequent histochemistry.2. Thirteen hair-follicle afferent fibres were stained including six that innervated tylotrichs (type T hair follicle afferent units) and one that innervated guard hairs (type G unit). The remaining six axons were not classified according to hair type, but, on the basis of their axonal conduction velocities, would have been either type G or T.3. Eleven axons could be traced back into the dorsal roots. Eight of these, upon entering the cord, turned and ran towards the brain. They did not divide into rostral and caudal branches. Three of the eleven did divide and gave rise to both rostral and caudal branches.4. Sixty-three collaterals were given off the thirteen stained axons. All well-filled collaterals had a strikingly similar morphology. They descended through laminae I-III of the dorsal horn into the deeper parts of lamina IV or into lamina V, before turning and ascending back into superficial lamina IV and lamina III where they branched profusely to give rise to their terminal arborizations. Terminal boutons, most commonly of the ;en passant' type, were numerous in lamina III, but were also seen in the dorsal part of lamina IV and in ventral lamina II. None were observed in dorsal lamina II or near the junction of the grey and white matter (lamina I) or in lamina V.5. The terminal arborizations of collaterals from a single hair follicle afferent fibre were in line with one another in the longitudinal axis of the cord. In the better-stained preparations the terminal arborizations of adjacent collaterals from a single axon formed a

  7. Tissue-engineered skin preserving the potential of epithelial cells to differentiate into hair after grafting.

    PubMed

    Larouche, Danielle; Cuffley, Kristine; Paquet, Claudie; Germain, Lucie

    2011-03-01

    The aim of this study was to evaluate whether tissue-engineered skin produced in vitro was able to sustain growth of hair follicles in vitro and after grafting. Different tissues were designed. Dissociated newborn mouse keratinocytes or newborn mouse hair buds (HBs) were added onto dermal constructs consisting of a tissue-engineered cell-derived matrix elaborated from either newborn mouse or adult human fibroblasts cultured with ascorbic acid. After 7-21 days of maturation at the air-liquid interface, no hair was noticed in vitro. Epidermal differentiation was observed in all tissue-engineered skin. However, human fibroblast-derived tissue-engineered dermis (hD) promoted a thicker epidermis than mouse fibroblast-derived tissue-engineered dermis (mD). In association with mD, HBs developed epithelial cyst-like inclusions presenting outer root sheath-like attributes. In contrast, epidermoid cyst-like inclusions lined by a stratified squamous epithelium were present in tissues composed of HBs and hD. After grafting, pilo-sebaceous units formed and hair grew in skin elaborated from HBs cultured 10-26 days submerged in culture medium in association with mD. However, the number of normal hair follicles decreased with longer culture time. This hair-forming capacity after grafting was not observed in tissues composed of hD overlaid with HBs. These results demonstrate that epithelial stem cells can be kept in vitro in a permissive tissue-engineered dermal environment without losing their potential to induce hair growth after grafting.

  8. Biology of the eyelash hair follicle: an enigma in plain sight.

    PubMed

    Paus, R; Burgoa, I; Platt, C I; Griffiths, T; Poblet, E; Izeta, A

    2016-04-01

    Because of their crucial impact on our perception of beauty, eyelashes constitute a prime target for the cosmetic industry. However, when compared with other hair shafts and the mini-organs that produce them [eyelash hair follicles (ELHFs)], knowledge on the biology underlying growth and pigmentation of eyelashes is still rudimentary. This is due in part to the extremely restricted availability of human ELHFs for experimental study, underappreciation of their important sensory and protective functions and insufficient interest in understanding why they are distinct from scalp hair follicles (HFs) (e.g. ELHFs produce shorter hair shafts, do not possess an arrector pili muscle, have a shorter hair cycle and undergo greying significantly later than scalp HFs). Here we synthesize the limited current knowledge on the biology of ELHFs, in humans and other species, their role in health and disease, the known similarities with and differences from other HF populations, and their intrinsic interethnic variations. We define major open questions in the biology of these intriguing mini-organs and conclude by proposing future research directions. These include dissecting the molecular and cellular mechanisms that underlie trichomegaly and the development of in vitro models in order to interrogate the distinct molecular controls of ELHF growth, cycling and pigmentation and to probe novel strategies for the therapeutic and cosmetic manipulation of ELHFs beyond prostaglandin receptor stimulation.

  9. Polycaprolactone fiber meshes provide a 3D environment suitable for cultivation and differentiation of melanocytes from the outer root sheath of hair follicle.

    PubMed

    Savkovic, Vuk; Flämig, Franziska; Schneider, Marie; Sülflow, Katharina; Loth, Tina; Lohrenz, Andrea; Hacker, Michael Christian; Schulz-Siegmund, Michaela; Simon, Jan-Christoph

    2016-01-01

    Melanocytes differentiated from the stem cells of human hair follicle outer root sheath (ORS) have the potential for developing non-invasive treatments for skin disorders out of a minimal sample: of hair root. With a robust procedure for melanocyte cultivation from the ORS of human hair follicle at hand, this study focused on the identification of a suitable biocompatible, biodegradable carrier as the next step toward their clinical implementation. Polycaprolactone (PCL) is a known biocompatible material used for a number of medical devices. In this study, we have populated electrospun PCL fiber meshes with normal human epidermal melanocytes (NHEM) as well as with hair-follicle-derived human melanocytes from the outer root sheath (HUMORS) and tested their functionality in vitro. PCL fiber meshes evidently provided a niche for melanocytes and supported their melanotic properties. The cells were tested for gene expression of PAX3, PMEL, TYR and MITF, as well as for proliferation, expression of melanocyte marker proteins tyrosinase and glycoprotein 100 (gp100), L-DOPA-tautomerase enzymatic activity and melanin content. Reduced mitochondrial activity and PAX-3 gene expression indicated that the three-dimensional PCL scaffold supported differentiation rather than proliferation of melanocytes. The monitored melanotic features of both the NHEM and HUMORS cultivated on PCL scaffolds significantly exceeded those of two-dimensional adherent cultures.

  10. Keratin-6 driven ODC expression to hair follicle keratinocytes enhances stemness and tumorigenesis by negatively regulating Notch

    SciTech Connect

    Arumugam, Aadithya; Weng, Zhiping; Chaudhary, Sandeep C.; Afaq, Farrukh; Elmets, Craig A.; Athar, Mohammad

    2014-08-29

    Highlights: • Targeting ODC to hair follicle augments skin carcinogenesis and invasive SCCs. • Hair follicle ODC expands stem cell compartment carrying CD34{sup +}/K15{sup +}/p63{sup +} keratinocytes. • Negatively regulated Notch1 is associated with expansion of stem cell compartment. - Abstract: Over-expression of ornithine decarboxylase (ODC) is known to be involved in the epidermal carcinogenesis. However, the mechanism by which it enhances skin carcinogenesis remains undefined. Recently, role of stem cells localized in various epidermal compartments has been shown in the pathogenesis of skin cancer. To direct ODC expression in distinct epidermal compartments, we have developed keratin 6 (K6)-ODC/SKH-1 and keratin 14 (K14)-ODC/SKH-1 mice and employed them to investigate the role of ODC directed to these epidermal compartments on UVB-induced carcinogenesis. K6-driven ODC over-expression directed to outer root sheath (ORS) of hair follicle was more effective in augmenting tumorigenesis as compared to mice where K14-driven ODC expression was directed to inter-follicular epidermal keratinocytes. Chronically UVB-irradiated K6-ODC/SKH-1 developed 15 ± 2.5 tumors/mouse whereas K14-ODC/SKH-1 developed only 6.8 ± 1.5 tumors/mouse. K6-ODC/SKH-1 showed augmented UVB-induced proliferation and much higher pro-inflammatory responses than K14-ODC/SKH-1 mice. Tumors induced in K6-ODC/SKH-1 were rapidly growing, invasive and ulcerative squamous cell carcinoma (SCC) showing decreased expression of epidermal polarity marker E-cadherin and enhanced mesenchymal marker, fibronectin. Interestingly, the number of CD34/CK15/p63 positive stem-like cells was significantly higher in chronically UVB-irradiated K6-ODC/SKH-1 as compared to K14-ODC/SKH-1 mice. Reduced Notch1 expression was correlated with the expansion of stem cell compartment in these animals. However, other signaling pathways such as DNA damage response or mTOR signaling pathways were not significantly different in

  11. The Tumor Suppressor Actions of the Vitamin D Receptor in Skin

    DTIC Science & Technology

    2014-10-01

    remarkable with disruption of hair follicles and hair follicle cycling. Survival for a number of these genotypes was limited, precluding completing the... hair at least initially. Histologically this was associated with increased numbers and markedly widened hair follicles (figure 1). However, with time...shown in figure 5. These mice also lose hair , and develop loss of hair follicles . The skin is hyperproliferative. The ears become quite abnormal

  12. Characterization of a new tissue-engineered human skin equivalent with hair.

    PubMed

    Michel, M; L'Heureux, N; Pouliot, R; Xu, W; Auger, F A; Germain, L

    1999-06-01

    We designed a new tissue-engineered skin equivalent in which complete pilosebaceous units were integrated. This model was produced exclusively from human fibroblasts and keratinocytes and did not contain any synthetic material. Fibroblasts were cultured for 35 d with ascorbic acid and formed a thick fibrous sheet in the culture dish. The dermal equivalent was composed of stacked fibroblast sheets and exhibited some ultrastructural organization found in normal connective tissues. Keratinocytes seeded on this tissue formed a stratified and cornified epidermis and expressed typical markers of differentiation (keratin 10, filaggrin, and transglutaminase). After 4 wk of culture, a continuous and ultrastructurally organized basement membrane was observed and associated with the expression of laminin and collagen IV and VII. Complete pilosebaceous units were obtained by thermolysin digestion and inserted in this skin equivalent in order to assess the role of the transfollicular route in percutaneous absorption. The presence of hair follicles abolished the lag-time observed during hydrocortisone diffusion and increased significantly its rate of penetration in comparison to the control (skin equivalent with sham hair insertion). Therefore, this new hairy human skin equivalent model allowed an experimental design in which the only variable was the presence of pilosebaceous units and provided new data confirming the importance of hair follicles in percutaneous absorption.

  13. Expression of mesenchymal stem cell marker CD90 on dermal sheath cells of the anagen hair follicle in canine species

    PubMed Central

    Mercati, F.; Pascucci, L.; Ceccarelli, P.; Dall’Aglio, C.; Pedini, V.; Gargiulo, A.M.

    2009-01-01

    The dermal sheath (DS) of the hair follicle is comprised by fibroblast-like cells and extends along the follicular epithelium, from the bulb up to the infundibulum. From this structure, cells with stem characteristics were isolated: they have a mesenchymal origin and express CD90 protein, a typical marker of mesenchymal stem cells. It is not yet really clear in which region of hair follicle these cells are located but some experimental evidence suggests that dermal stem cells are localized prevalently in the lower part of the anagen hair follicle. As there are no data available regarding DS stem cells in dog species, we carried out a morphological analysis of the hair follicle DS and performed both an immunohistochemical and an immunocytochemical investigation to identify CD90+ cells. We immunohistochemically evidenced a clear and abundant positivity to CD90 protein in the DS cells located in the lower part of anagen hair follicle. The positive cells showed a typical fibroblast-like morphology. They were flat and elongated and inserted among bundles of collagen fibres.The whole structure formed a close and continuous sleeve around the anagen hair follicle. Our immunocytochemical study allowed us to localize CD90 protein at the cytoplasmic membrane level.

  14. Expression of mesenchymal stem cell marker CD90 on dermal sheath cells of the anagen hair follicle in canine species.

    PubMed

    Mercati, F; Pascucci, L; Ceccarelli, P; Dall'Aglio, C; Pedini, V; Gargiulo, A M

    2009-09-23

    The dermal sheath (DS) of the hair follicle is comprised by fibroblast-like cells and extends along the follicular epithelium, from the bulb up to the infundibulum. From this structure, cells with stem characteristics were isolated: they have a mesenchymal origin and express CD90 protein, a typical marker of mesenchymal stem cells. It is not yet really clear in which region of hair follicle these cells are located but some experimental evidence suggests that dermal stem cells are localized prevalently in the lower part of the anagen hair follicle. As there are no data available regarding DS stem cells in dog species, we carried out a morphological analysis of the hair follicle DS and performed both an immunohistochemical and an immunocytochemical investigation to identify CD90+ cells. We immunohistochemically evidenced a clear and abundant positivity to CD90 protein in the DS cells located in the lower part of anagen hair follicle. The positive cells showed a typical fibroblast-like morphology. They were flat and elongated and inserted among bundles of collagen fibres. The whole structure formed a close and continuous sleeve around the anagen hair follicle. Our immunocytochemical study allowed us to localize CD90 protein at the cytoplasmic membrane level.

  15. Topical Application of Oleuropein Induces Anagen Hair Growth in Telogen Mouse Skin

    PubMed Central

    Tong, Tao; Kim, Nahyun; Park, Taesun

    2015-01-01

    We observed that oleuropein, the main constituent of the leaves and unprocessed olive drupes of Olea europaea, protected mice from high-fat diet-induced adiposity by up-regulation of genes involved in Wnt10b-mediated signaling in adipose tissue. The activation of Wnt/β-catenin pathway is also well established to positively regulate the anagen phase of hair growth cycle in mice skin. Methodology and Principal Findings Oleuropein promoted cultured human follicle dermal papilla cell proliferation and induced LEF1 and Cyc-D1 mRNA expression and β-catenin protein expression in dermal papilla cells. Nuclear accumulation of β-catenin in dermal papilla cells was observed after oleuropein treatment. Topical application of oleuropein (0.4 mg/mouse/day) to C57BL/6N mice accelerated the hair-growth induction and increased the size of hair follicles in telogenic mouse skin. The oleuropein-treated mouse skin showed substantial upregulation of Wnt10b, FZDR1, LRP5, LEF1, Cyc-D1, IGF-1, KGF, HGF, and VEGF mRNA expression and β-catenin protein expression. Conclusions and Significance These results demonstrate that topical oleuroepin administration induced anagenic hair growth in telogenic C57BL/6N mouse skin. The hair-growth promoting effect of oleuropein in mice appeared to be associated with the stimulation of the Wnt10b/β-catenin signaling pathway and the upregulation of IGF-1, KGF, HGF, and VEGF gene expression in mouse skin tissue. PMID:26060936

  16. Hair follicle: a reliable source of recipient origin after allogeneic hematopoietic stem cell transplantation.

    PubMed

    Hong, Y C; Liu, H M; Chen, P S; Chen, Y J; Lyou, J Y; Hu, H Y; Yi, M F; Lin, J S; Tzeng, C-H

    2007-11-01

    Blood, buccal swab and hair follicles are among the most commonly used sources for forensic science, parentage testing and personal identification. A total of 29 patients who have had a sustained engraftment from 15 months to 21.5 years after allogeneic hematopoietic stem cell transplantation (HSCT) without rejection, relapse or chronic GVHD involving oral mucosa were enrolled for a chimerism study. PCR-amplified short tandem repeat analyses were conducted per patient every 3 months for at least three consecutive times. The results for blood were all donor type except one who had a mixed chimerism, 14.5 years after receiving a transplant for lymphoma. As for buccal swab, mixed chimerism ranging from 10 to 96% donor origin was noted for 28 recipients except the one who had mixed chimerism of blood and retained total recipient type. In contrast, hair follicles were 100% recipient type for the entire group. It is concluded that the hair follicle is devoid of adult stem cell plasticity and may serve as a reliable source of recipient's origin when pre-transplant DNA fingerprinting or reference DNA is not available for people who have successfully received allogeneic HSCT while in need of a personal identification.

  17. An approach to unsupervised hair removal from skin melanoma image

    NASA Astrophysics Data System (ADS)

    Xie, Feng-Ying; Qin, Shi-Yin; Jiang, Zhi-Guo; Meng, Ru-Song; Xu, Bin

    2008-10-01

    Hair removal from skin melanoma image is one of the key problems for the precise segmentation and analysis of the skin malignant melanoma. In this paper, an automatically hair removal algorithm in dermoscopy images of pigmented skin lesions is proposed. This algorithm includes three steps: firstly, the melanoma image with hairs are enhanced by morphologic closing-based top-hat operator and then segmented through statistic threshold; secondly, the hairs are extracted based on the elongate of connected region; thirdly, the hair-occluded information is repaired by replacing the hair pixels with the nearby non-hair pixels. As a matter of fact, with the morphologic closing-based top-hat operator both strong and weak hairs can be enhanced simultaneously, and the elongate state of band-like connected region can be correctly described by the elongate function proposed in this paper so as to measure the hair effectively. Therefore, the unsupervised hair removal problem in dermoscopy melanoma image can be resolved very well through combining the hair extraction with information repair. The experiment results show that various hairs can be extracted accurately and the repaired effect of textures can satisfy the requirement of medical diagnosis.

  18. Induced pluripotent stem cells from human hair follicle mesenchymal stem cells.

    PubMed

    Wang, Yimei; Liu, Jinyu; Tan, Xiaohua; Li, Gaofeng; Gao, Yunhe; Liu, Xuejuan; Zhang, Lihong; Li, Yulin

    2013-08-01

    Reprogramming of somatic cells into inducible pluripotent stem cells (iPSCs) provides an alternative to using embryonic stem cells (ESCs). Mesenchymal stem cells derived from human hair follicles (hHF-MSCs) are easily accessible, reproducible by direct plucking of human hairs. Whether these hHF-MSCs can be reprogrammed has not been previously reported. Here we report the generation of iPSCs from hHF-MSCs obtained by plucking several hairs. hHF-MSCs were isolated from hair follicle tissues and their mesenchymal nature confirmed by detecting cell surface antigens and multilineage differentiation potential towards adipocytes and osteoblasts. They were then reprogrammed into iPSCs by lentiviral transduction with Oct4, Sox2, c-Myc and Klf4. hHF-MSC-derived iPSCs appeared indistinguishable from human embryonic stem cells (hESCs) in colony morphology, expression of alkaline phosphotase, and expression of specific hESCs surface markers, SSEA-3, SSEA-4, Tra-1-60, Tra-1-81, Nanog, Oct4, E-Cadherin and endogenous pluripotent genes. When injected into immunocompromised mice, hHF-MSC-derived iPSCs formed teratomas containing representatives of all three germ layers. This is the first study to report reprogramming of hHF-MSCs into iPSCs.

  19. miR-24 affects hair follicle morphogenesis targeting Tcf-3.

    PubMed

    Amelio, I; Lena, A M; Bonanno, E; Melino, G; Candi, E

    2013-11-14

    During embryonic development, hair follicles (HFs) develop from an epidermal-mesenchymal cross talk between the ectoderm progenitor layer and the underlying dermis. Epidermal stem cell activation represents a crucial point both for HF morphogenesis and for hair regeneration. miR-24 is an anti-proliferative microRNA (miRNA), which is induced during differentiation of several cellular systems including the epidermis. Here, we show that miR-24 is expressed in the HF and has a role in hair morphogenesis. We generated transgenic mice ectopically expressing miR-24 under the K5 promoter. The K5::miR-24 animals display a marked defect in HF morphogenesis, with thinning of hair coat and altered HF structure. Expression of miR-24 alters the normal process of hair keratinocyte differentiation, leading to altered expression of differentiation markers. MiR-24 directly represses the hair keratinocyte stemness regulator Tcf-3. These results support the notion that microRNAs, and among them miR-24, have an important role in postnatal epidermal homeostasis.

  20. Signalling couples hair follicle stem cell quiescence with reduced histone H3 K4/K9/K27me3 for proper tissue homeostasis.

    PubMed

    Lee, Jayhun; Kang, Sangjo; Lilja, Karin C; Colletier, Keegan J; Scheitz, Cornelia Johanna Franziska; Zhang, Ying V; Tumbar, Tudorita

    2016-04-15

    Mechanisms of plasticity to acquire different cell fates are critical for adult stem cell (SC) potential, yet are poorly understood. Reduced global histone methylation is an epigenetic state known to mediate plasticity in cultured embryonic SCs and T-cell progenitors. Here we find histone H3 K4/K9/K27me3 levels actively reduced in adult mouse skin and hair follicle stem cells (HFSCs) during G0 quiescence. The level of marks over specific gene promoters did not correlate to mRNA level changes in quiescent HFSCs. Skin hypomethylation during quiescence was necessary for subsequent progression of hair homeostasis (cycle). Inhibiting BMP signal, a known HFSC anti-proliferative factor, elevated HFSC methylation in vivo during quiescence prior to proliferation onset. Furthermore, removal of proliferation factors and addition of BMP4 reduced histone methylases and increased demethylases mRNAs in cultured skin epithelial cells. We conclude that signalling couples hair follicle stem cell quiescence with reduced H3 K4/K9/K27me3 levels for proper tissue homeostasis.

  1. Signalling couples hair follicle stem cell quiescence with reduced histone H3 K4/K9/K27me3 for proper tissue homeostasis

    PubMed Central

    Lee, Jayhun; Kang, Sangjo; Lilja, Karin C.; Colletier, Keegan J.; Scheitz, Cornelia Johanna Franziska; Zhang, Ying V.; Tumbar, Tudorita

    2016-01-01

    Mechanisms of plasticity to acquire different cell fates are critical for adult stem cell (SC) potential, yet are poorly understood. Reduced global histone methylation is an epigenetic state known to mediate plasticity in cultured embryonic SCs and T-cell progenitors. Here we find histone H3 K4/K9/K27me3 levels actively reduced in adult mouse skin and hair follicle stem cells (HFSCs) during G0 quiescence. The level of marks over specific gene promoters did not correlate to mRNA level changes in quiescent HFSCs. Skin hypomethylation during quiescence was necessary for subsequent progression of hair homeostasis (cycle). Inhibiting BMP signal, a known HFSC anti-proliferative factor, elevated HFSC methylation in vivo during quiescence prior to proliferation onset. Furthermore, removal of proliferation factors and addition of BMP4 reduced histone methylases and increased demethylases mRNAs in cultured skin epithelial cells. We conclude that signalling couples hair follicle stem cell quiescence with reduced H3 K4/K9/K27me3 levels for proper tissue homeostasis. PMID:27080563

  2. Human hair follicle pigmentary unit as a direct target for modulators of melanogenesis, as studied by [14C]-2-thiouracil incorporation.

    PubMed

    Michelet, Jean-François; Gautier, Brigitte; Gaillard, Olivier; Bernard, Bruno Alain; Benech, Florence

    2009-04-01

    The purpose of this study was to evaluate human hair follicle melanogenic activity using the [14C]-2-thiouracil, which was known to incorporate into nascent melanins. Results obtained on pigmented, grey and non-pigmented hair follicles demonstrated that [(14)C]-2-TU incorporation was restricted to the melanogenic compartment with a strong accumulation located around dermal papilla and within the fibre of pigmented hair follicles. Quantitative analysis of [(14)C]-2-TU incorporation showed a significant increase in pigmented hair follicles upon stimulation with 1 microm forskolin concomitant to an increase in tyrosinase levels. A strong significant decrease in [14C]-2-TU incorporation was noted, when hair follicles were incubated with the tyrosinase competitive inhibitor kojic acid (200 microm). Incubation with the MC1-R agonist alpha-MSH (0.2 microm) did not induce a significant stimulation of hair melanogenesis. The present model could thus represent a useful new tool to identify modulators of human hair pigmentation.

  3. Label-free identification and characterization of murine hair follicle stem cells located in thin tissue sections with Raman micro-spectroscopy.

    PubMed

    Tsai, Tsung-Hua; Short, Michael A; McLean, David I; Zeng, Haishan; McElwee, Kevin; Lui, Harvey

    2014-06-07

    Stem cells offer tremendous opportunities for regenerative medicine. Over the past decade considerable research has taken place to identify and characterize the differentiation states of stem cells in culture. Raman micro-spectroscopy has emerged as an ideal technology since it is fast, nondestructive, and does not require potentially toxic dyes. Raman spectroscopy systems can also be incorporated into confocal microscope imaging systems allowing spectra to be obtained from below the tissue surface. Thus there is significant potential for monitoring stem cells in living tissue. Stem cells that reside in hair follicles are suitable for testing this possibility since they are close to the skin surface, and typically clustered around the bulge area. One of the first steps needed would be to obtain Raman micro-spectra from stem cells located in thin sections of tissue, and then see whether these spectra are clearly different from those of the surrounding differentiated cells. To facilitate this test, standard 5 μm thick sections of murine skin tissue were stained to identify the location of hair follicle stem cells and their progeny. Raman spectra were then obtained from adjacent cells in a subsequent unstained 10 μm thick section. The spectra revealed significant differences in peak intensities associated with nucleic acids, proteins, lipids and amino acids. Statistical analyses of the Raman micro-spectra identified stem cells with 98% sensitivity and 94% specificity, as compared with a CD34 immunostaining gold standard. Furthermore analyses of the spectral variance indicated differences in cellular dynamics between the two cell groups. This study shows that Raman micro-spectroscopy has a potential role in identifying adult follicle stem cells, laying the groundwork for future applications of hair follicle stem cells and other somatic stem cells in situ.

  4. Defining BMP functions in the hair follicle by conditional ablation of BMP receptor IA.

    PubMed

    Kobielak, Krzysztof; Pasolli, H Amalia; Alonso, Laura; Polak, Lisa; Fuchs, Elaine

    2003-11-10

    Using conditional gene targeting in mice, we show that BMP receptor IA is essential for the differentiation of progenitor cells of the inner root sheath and hair shaft. Without BMPRIA activation, GATA-3 is down-regulated and its regulated control of IRS differentiation is compromised. In contrast, Lef1 is up-regulated, but its regulated control of hair differentiation is still blocked, and BMPRIA-null follicles fail to activate Lef1/beta-catenin-regulated genes, including keratin genes. Wnt-mediated transcriptional activation can be restored by transfecting BMPRIA-null keratinocytes with a constitutively activated beta-catenin. This places the block downstream from Lef1 expression but upstream from beta-catenin stabilization. Because mice lacking the BMP inhibitor Noggin fail to express Lef1, our findings support a model, whereby a sequential inhibition and then activation of BMPRIA is necessary to define a band of hair progenitor cells, which possess enough Lef1 and stabilized beta-catenin to activate the hair specific keratin genes and generate the hair shaft.

  5. Assembling Composite Dermal Papilla Spheres with Adipose-derived Stem Cells to Enhance Hair Follicle Induction

    PubMed Central

    Huang, Chin-Fu; Chang, Ya-Ju; Hsueh, Yuan-Yu; Huang, Chia-Wei; Wang, Duo-Hsiang; Huang, Tzu-Chieh; Wu, Yi-Ting; Su, Fong-Chin; Hughes, Michael; Chuong, Cheng-Ming; Wu, Chia-Ching

    2016-01-01

    Intradermal adipose tissue plays an essential role for hair follicles (HFs) regeneration by regulating hair cycles. However, the effect of reconstruction of HFs and the involvement of adipose-related cells are poorly understood. We investigated assembly strategies for the interactions of dermal papilla (DP) cells with adipose-derived stem cells (ASCs) in promoting hair formation. DP cells lose DP traits during adherent culture, but preserved DP markers with a unified sphere diameter by seeding on chitosan-coated microenvironments. Next, ASCs isolated from rats were co-cultured with DP spheres by different assembling approaches to determine their interactions; a mixed sphere of ASCs with DP cells (MA-DPS), or a core-shell structure, outer ASCs shell and an inner DP core (CSA-DPS). CSA-DPS exhibited superior DP characteristics compared to MA-DPS. Conditional medium from ASCs, but not differentiated adipocytes, promoted DP markers and functional alkaline phosphatase activity from the DP cells. In vivo patch assay showed the core-shell assembling of CSA-DPS can reconstruct cellular arrangements and microenvironmental niches as dominated by PPARα signal in ASCs to induce the greater hair induction than MA-DPS or DP spheres alone. Therefore, the assembling of a core-shell sphere for DP with ASCs could reconstruct the HF cellular arrangement for hair formation. This paper set the groundwork for further evaluation of the input of other cell types. PMID:27210831

  6. Discovery of differentially expressed genes in cashmere goat (Capra hircus) hair follicles by RNA sequencing.

    PubMed

    Qiao, X; Wu, J H; Wu, R B; Su, R; Li, C; Zhang, Y J; Wang, R J; Zhao, Y H; Fan, Y X; Zhang, W G; Li, J Q

    2016-09-02

    The mammalian hair follicle (HF) is a unique, highly regenerative organ with a distinct developmental cycle. Cashmere goat (Capra hircus) HFs can be divided into two categories based on structure and development time: primary and secondary follicles. To identify differentially expressed genes (DEGs) in the primary and secondary HFs of cashmere goats, the RNA sequencing of six individuals from Arbas, Inner Mongolia, was performed. A total of 617 DEGs were identified; 297 were upregulated while 320 were downregulated. Gene ontology analysis revealed that the main functions of the upregulated genes were electron transport, respiratory electron transport, mitochondrial electron transport, and gene expression. The downregulated genes were mainly involved in cell autophagy, protein complexes, neutrophil aggregation, and bacterial fungal defense reactions. According to the Kyoto Encyclopedia of Genes and Genomes database, these genes are mainly involved in the metabolism of cysteine and methionine, RNA polymerization, and the MAPK signaling pathway, and were enriched in primary follicles. A microRNA-target network revealed that secondary follicles are involved in several important biological processes, such as the synthesis of keratin-associated proteins and enzymes involved in amino acid biosynthesis. In summary, these findings will increase our understanding of the complex molecular mechanisms of HF development and cycling, and provide a basis for the further study of the genes and functions of HF development.

  7. [Anhidrotic ectodermal dysplasia. Disorder of the differentiation of hair follicles and sweat glands leads to abnormal keratinization].

    PubMed

    Blume-Peytavi, U; Gollnick, H M; Föhles, J; Kremer, G; Pineda, M S; Phan, K H; Orfanos, C E

    1994-06-01

    We report on an 11-year-old female patient with anhidrotic ectodermal dysplasia (AED) showing the following characteristics: (1) reduced number of hair follicles and incomplete formation of sweat glands; (2) disturbed hair growth with shortening of anagen and anhidrosis; (3) disturbed cytokeratin expression pattern of CK 13, 14, 19 (follicular epithelium) and of CK 18 (eccrine sweat glands); (4) reduction of cystine and increase in sulphonic cysteine acid. Thus, we demonstrated pathological differentiation on the immunomorphological and on the biochemical level, leading to disturbed keratinization that could be visualized by transmission and scanning electron microscopical studies of the hair shafts. According to these findings AED is a developmental defect that involves not only incomplete formation of hair follicles and sweat glands but also a disordered differentiation and follicular keratinization with disturbed cytokeratin pattern and pathological amino acid composition of the terminal hairs produced.

  8. The electron microscopy of the human hair follicle. III. The inner root sheath and trichohyaline.

    PubMed

    BIRBECK, M S; MERCER, E H

    1957-03-25

    1. The three cylinders of cells, each one cell thick, which together constitute the inner root sheath, arise from the peripheral portions of the undifferentiated matrix. These cells, like the hair cuticle, are stabilised by the spread of adhesive contacts between their plasma membranes which occurs in the mid-bulb and upper bulb of the hair follicle. 2. The characteristic intracellular product of all three cell layers is trichohyaline. This substance is formed in the first place as amorphous droplets which subsequently transform into a birefringent form. 3. This transformation, involving the formation of a birefringent product from an amorphous precursor, is in contrast to the formation in the cortex of keratin which originates in a fibrous form. 4. Trichohyaline appears first and transforms first in the cells of Henle which are nearest the outer sheath and the dermal supply vessels. This transformation occurs at the level of the neck of the follicle. Synthesis and transformation in the cells of Huxley and the sheath cuticle lag behind the similar events in the cells of Henle. The transformation does not begin until the lower prekeratinous zone in the Huxley and cuticle cells. 5. The amorpous-fibrous transformation occurs rapidly cell by cell and involves the conversion of all the trichohyaline droplets. In longitudinal sections the birefringent modification can be seen extending from the droplets in both directions parallel to the axis of the hair. In cross-sections the images of the transformed material are difficult to interpret. They may be seen as sections of corrugated sheets ( approximately 100 A thick) or condensed fibrils approximately 100 A in width. 6. At the same time that the trichohyaline transforms, the spacing between the cell membranes increases and a dark deposit appears centrally between them. This membrane complex, and the similar complex of the hair cuticle cells described in Part 2, may be specialised formations whose purpose is to hold the

  9. Bisindolylmaleimide protein-kinase-C inhibitors delay the decline in DNA synthesis in mouse hair follicle organ cultures.

    PubMed

    Harmon, C S; Nevins, T D; Ducote, J; Lutz, D

    1997-01-01

    We have used a series of bisindolylmaleimide selective protein-kinase C (PKC) inhibitors to investigate the role of this enzyme in the regulation of cell proliferation in mouse hair follicle organ cultures. Mouse whisker follicles were isolated by microdissection, and rates of DNA synthesis during culture were determined from 3H-thymidine incorporation. The bisindolylmaleimides Ro 31-7549, Ro 31-8161, Ro 31-8425 and Ro 31-8830 inhibit isolated brain PKC with IC50 values of 8-80 nM, are > 60-fold less potent against protein kinase A, and inhibit PKC-mediated protein phosphorylation in platelets with IC50 values in the range 0.25-4.4 microM. These PKC inhibitors were found to increase levels of mouse hair follicle DNA synthesis, with EC50 values in the range 1-4 microM and maximal levels in the range 151-197% of control. Ro 31-7549 had an IC50 value 50-fold lower than that of minoxidil, while the maximal level of DNA synthesis for the PKC inhibitor was 86% higher. Incubation of mouse hair follicles with Ro 31-7549 resulted in a delay of approximately 24 h in the onset of decline in follicular DNA synthesis rates. Ro 31-6045 and Ro 31-7208, bisindolylmaleimides without activity in the platelet PKC assay, did not affect mouse hair follicle DNA synthesis rates. Taken together, these findings show that PKC mediates, at least in part, the rapid loss of proliferative activity that occurs in mouse whisker follicles in culture, and provide further evidence that PKC plays a role as a negative proliferative signal in hair follicles.

  10. Embryonic attenuated Wnt/β-catenin signaling defines niche location and long-term stem cell fate in hair follicle

    PubMed Central

    Xu, Zijian; Wang, Wenjie; Jiang, Kaiju; Yu, Zhou; Huang, Huanwei; Wang, Fengchao; Zhou, Bin; Chen, Ting

    2015-01-01

    Long-term adult stem cells sustain tissue regeneration throughout the lifetime of an organism. They were hypothesized to originate from embryonic progenitor cells that acquire long-term self-renewal ability and multipotency at the end of organogenesis. The process through which this is achieved often remains unclear. Here, we discovered that long-term hair follicle stem cells arise from embryonic progenitor cells occupying a niche location that is defined by attenuated Wnt/β-catenin signaling. Hair follicle initiation is marked by placode formation, which depends on the activation of Wnt/β-catenin signaling. Soon afterwards, a region with attenuated Wnt/β-catenin signaling emerges in the upper follicle. Embryonic progenitor cells residing in this region gain expression of adult stem cell markers and become definitive long-term hair follicle stem cells at the end of organogenesis. Attenuation of Wnt/β-catenin signaling is a prerequisite for hair follicle stem cell specification because it suppresses Sox9, which is required for stem cell formation. DOI: http://dx.doi.org/10.7554/eLife.10567.001 PMID:26653852

  11. Alterations of plasma antioxidants and mitochondrial DNA mutation in hair follicles of smokers.

    PubMed

    Liu, Chin-San; Chen, Haw-Wen; Lii, Chong-Kuei; Tsai, Ching-Shan; Kuo, Chen-Ling; Wei, Yau-Huei

    2002-01-01

    The effects of long-term smoking on mitochondrial DNA (mtDNA) deletions in hair follicles were investigated in subjects with different antioxidant capacity. Twenty-two male smokers with a smoking index of greater than 5 pack-years and without any known systemic diseases were recruited for this study. Forty healthy nonsmoking males were included as controls. We found that the concentrations of ascorbate and alpha-tocopherol and the activities of glutathione S-transferase (GST) and glutathione peroxidase in blood plasma were significantly decreased in smokers. The levels of glutathione and protein thiols in whole blood and the incidence of a 4,977 bp deletion of mtDNA (dmtDNA) in hair follicles were significantly increased in smokers. A significantly higher incidence of the 4,977 bp dmtDNA was found in smokers with plasma GST activity less than 5.66 U/l (OR = 7.2, P = 0.020). Using multiple covariate ANOVA and logistic regression, we found that age and low plasma GST activity were the only two risk factors for the 4,977 bp dmtDNA. These results suggest that smoking depletes antioxidants and causes mtDNA deletions and that plasma GST may play an important role in the preservation of the mitochondrial genome in tissue cells of smokers.

  12. Protopanaxatirol type ginsenoside Re promotes cyclic growth of hair follicles via inhibiting transforming growth factor β signaling cascades.

    PubMed

    Li, Zheng; Ryu, Seung-Wook; Lee, Jungsul; Choi, Kyungsun; Kim, Sunchang; Choi, Chulhee

    2016-02-19

    Ginsenosides, the major bio-active ingredients included in Panax ginseng, have been known for the hair growth activity and used to treat patients who suffer from hair loss; however, the detailed mechanisms of this action are still largely unknown. This study was conducted to investigate the molecular and cellular mechanisms responsible for hair growth promoting effect of ginsenoside Re (GRe) in vitro and in vivo. Different doses of minoxidil and GRe were administered topically to the back regions of nude mice for up to 45 days, and hair shaft length and hair cycles were determined for hair promoting activities. Topical treatment of GRe significantly increased the hair shaft length and hair existent time, which was comparable to the action of minoxidil. We also demonstrated that GRe stimulated hair shaft elongation in the ex vivo cultures of vibrissa hair follicles isolated from C57BL/6 mouse. Systemic transcriptome analysis by next generation sequencing demonstrated that TGF-β-pathway related genes were selectively down-regulated by treatment of GRe in vivo, and the same treatment suppressed TGF-β-induced phosphorylation of ERK in HeLa cells. The results clearly indicated that GRe is the effective constituent in the ginseng on hair promotion via selective inhibition of the hair growth phase transition related signaling pathways, TGF-β signaling cascades.

  13. Epithelial-mesenchymal transition in keloid tissues and TGF-β1-induced hair follicle outer root sheath keratinocytes.

    PubMed

    Yan, Li; Cao, Rui; Wang, Lianzhao; Liu, Yuanbo; Pan, Bo; Yin, Yanhua; Lv, Xiaoyan; Zhuang, Qiang; Sun, Xuejian; Xiao, Ran

    2015-01-01

    Keloid is a skin fibrotic disease with the characteristics of recurrence and invasion, its pathogenesis still remains unrevealed. The epithelial-mesenchymal transition (EMT) is critical for wound healing, fibrosis, recurrence, and invasion of cancer. We sought to investigate the EMT in keloid and the mechanism through which the EMT regulates keloid formation. In keloid tissues, the expressions of EMT-associated markers and transforming growth factor (TGF)-β1/Smad3 signaling were examined by immunohistochemistry. In the keloid epidermis and dermal tissue, the expressions of genes related to the regulation of skin homeostasis, fibroblast growth factor receptor 2 (FGFR2) and p63, were analyzed using quantitative real-time polymerase chain reaction. The results showed that accompanying the loss of the epithelial marker E-cadherin and the gain of the mesenchymal markers fibroblast-specific protein 1 (FSP1) and vimentin in epithelial cells from epidermis and skin appendages, and in endothelial cells from dermal microvessels, enhanced TGF-β1 expression and Smad3 phosphorylation were noted in keloid tissues. Moreover, alternative splicing of the FGFR2 gene switched the predominantly expressed isoform from FGFR2-IIIb to -IIIc, concomitant with the decreased expression of ΔNp63 and TAp63, which changes might partially account for abnormal epidermis and appendages in keloids. In addition, we found that TGF-β1-induced hair follicle outer root sheath keratinocytes (ORSKs) and normal skin epithelial cells underwent EMT in vitro with ORSKs exhibiting more obvious EMT changes and more similar expression profiles for EMT-associated and skin homeostasis-related genes as in keloid tissues, suggesting that ORSKs might play crucial roles in the EMT in keloids. Our study provided insights into the molecular mechanisms mediating the EMT pathogenesis of keloids.

  14. The Modulatable Stem Cell Niche: Tissue Interactions during Hair and Feather Follicle Regeneration.

    PubMed

    Chen, Chih-Chiang; Plikus, Maksim V; Tang, Pin-Chi; Widelitz, Randall B; Chuong, Cheng Ming

    2016-04-10

    Hair and feathers are unique because (1) their stem cells are contained within a follicle structure, (2) they undergo cyclic regeneration repetitively throughout life, (3) regeneration occurs physiologically in healthy individuals and (4) regeneration is also induced in response to injury. Precise control of this cyclic regeneration process is essential for maintaining the homeostasis of living organisms. While stem cells are regulated by the intra-follicle-adjacent micro-environmental niche, this niche is also modulated dynamically by extra-follicular macro-environmental signals, allowing stem cells to adapt to a larger changing environment and physiological needs. Here we review several examples of macro-environments that communicate with the follicles: intradermal adipose tissue, innate immune system, sex hormones, aging, circadian rhythm and seasonal rhythms. Related diseases are also discussed. Unveiling the mechanisms of how stem cell niches are modulated provides clues for regenerative medicine. Given that stem cells are hard to manipulate, focusing translational therapeutic applications at the environments appears to be a more practical approach.

  15. Distribution of proteoglycans during the hair growth cycle in human skin.

    PubMed

    Westgate, G E; Messenger, A G; Watson, L P; Gibson, W T

    1991-02-01

    The involvement of proteoglycans in hair growth has been recognized through the observation of increased hair growth in diseases such as the mucopolysaccharidoses and pre-tibial myxedema, which involve an increase in skin proteoglycan content. In an attempt to understand this, we have examined the distribution of chondroitin 6 sulphate (C6S), unsulphated chondroitin (COS), dermatan sulphate (DS), and heparan sulphate proteoglycans (HSPG) in frozen tissue sections of normal scalp by immunostaining. Results show that during anagen, the thick connective tissue sheath around the follicle strains strongly for C6S, COS, and DS. COS is uniquely associated with this region and is not found beneath the epidermis or infundibular epithelium. HSPG is, however, localized in the basement membrane zone adjacent to the outer root sheath. In addition, all of these proteoglycans are localized in the dermal papilla. In mid-catagen, we observed significant loss of C6S and COS staining from both the dermal papilla and the connective tissue sheath, but no decrease in staining for HSPG. In late catagen, very little staining of C6S and COS was observed. In early anagen, we observed that C6S was again present in the connective tissue sheath and dermal papilla; however, COS staining appeared to be weaker and less closely associated with the follicle. HSPG staining was observed in early anagen in a pattern very similar to that found for other basement membrane components. Results for DS were not obtained for catagen or early anagen. These results provide further evidence that hair growth is associated with the presence of chondroitin proteoglycans in the follicle environment and that the cessation of growth is associated with their removal. Further studies are underway to characterize the relationship between hair growth and proteoglycans.

  16. Human epithelial hair follicle stem cells and their progeny: current state of knowledge, the widening gap in translational research and future challenges.

    PubMed

    Purba, Talveen S; Haslam, Iain S; Poblet, Enrique; Jiménez, Francisco; Gandarillas, Alberto; Izeta, Ander; Paus, Ralf

    2014-05-01

    Epithelial hair follicle stem cells (eHFSCs) are required to generate, maintain and renew the continuously cycling hair follicle (HF), supply cells that produce the keratinized hair shaft and aid in the reepithelialization of injured skin. Therefore, their study is biologically and clinically important, from alopecia to carcinogenesis and regenerative medicine. However, human eHFSCs remain ill defined compared to their murine counterparts, and it is unclear which murine eHFSC markers really apply to the human HF. We address this by reviewing current concepts on human eHFSC biology, their immediate progeny and their molecular markers, focusing on Keratin 15 and 19, CD200, CD34, PHLDA1, and EpCAM/Ber-EP4. After delineating how human eHFSCs may be selectively targeted experimentally, we close by defining as yet unmet key challenges in human eHFSC research. The ultimate goal is to transfer emerging concepts from murine epithelial stem cell biology to human HF physiology and pathology.

  17. The cycling hair follicle as an ideal systems biology research model.

    PubMed

    Al-Nuaimi, Yusur; Baier, Gerold; Watson, Rachel E B; Chuong, Cheng-Ming; Paus, Ralf

    2010-08-01

    In the postgenomic era, systems biology has rapidly emerged as an exciting field predicted to enhance the molecular understanding of complex biological systems by the use of quantitative experimental and mathematical approaches. Systems biology studies how the components of a biological system (e.g. genes, transcripts, proteins, metabolites) interact to bring about defined biological function or dysfunction. Living systems may be divided into five dimensions of complexity: (i) molecular; (ii) structural; (iii) temporal; (iv) abstraction and emergence; and (v) algorithmic. Understanding the details of these dimensions in living systems is the challenge that systems biology aims to address. Here, we argue that the hair follicle (HF), one of the signature features of mammals, is a perfect and clinically relevant model for systems biology research. The HF represents a stem cell-rich, essentially autonomous mini-organ, whose cyclic transformations follow a hypothetical intrafollicular "hair cycle clock" (HCC). This prototypic neuroectodermal-mesodermal interaction system, at the cross-roads of systems and chronobiology, encompasses various levels of complexity as it is subject to both intrafollicular and extrafollicular inputs (e.g. intracutaneous timing mechanisms with neural and systemic stimuli). Exploring how the cycling HF addresses the five dimensions of living systems, we argue that a systems biology approach to the study of hair growth and cycling, in man and mice, has great translational medicine potential. Namely, the easily accessible human HF invites preclinical and clinical testing of novel hypotheses generated with this approach.

  18. [Cellular dynamics of the outer layers of the hair follicle of fine-wool sheep during the phase of stable hair growth].

    PubMed

    Vsevolodov, É B; Golichenkov, V A; Latypov, I F

    2014-01-01

    The structure, origin, and migration of outer sheath cells of the hair follicles of domestic sheep were studied by electron microscopic, autoradiographic, and histochemical (glycogen) in order to understand the role of this layer in hair morphogenesis. We demonstrated that the cells of the outer layers of the outer sheath interpose into the inner "companion" layer of the outer sheath. Although this process takes place all along the hair follicle from the lower bulb up to the sebaceous glands orifices, it mainly takes place over the bulb. Labeled cells interposed into the companion layer move towards sebaceous glands orifices more than 24 hours faster than labeled cells of the inner sheath and hair, because these cells included the label not in the bulb cambium (as hair and inner sheath) but over the bulb, and from this point they start movement. Interposition of cells into the companion layer must cause increase of its volume and additional volume supposed to be led away into the pillar canal around the hair near the sebaceous glands orifices. This can provide the mechanism for the propagation of the hair and inner sheath promotion to sebaceous gland orifices.

  19. Changing patterns of gap junctional intercellular communication and connexin distribution in mouse epidermis and hair follicles during embryonic development.

    PubMed

    Choudhry, R; Pitts, J D; Hodgins, M B

    1997-12-01

    In the mouse embryo between embryonic days 12 (E12) and 16, regular arrays of epidermal placodes on the mystacial pad develop into whisker follicles. This system was chosen for analysis of gap junctional intercellular communication during differentiation. The patterns of communication were studied by microinjection of the tracers Lucifer yellow-CH (LY-CH) and neurobiotin (NB), while immunofluorescent staining was used to study distribution of connexins 26 and 43. Extensive communication was seen between keratinocytes in developing hair pegs or, in later-stage hair follicles, in the germinative matrix. Coupling between adjacent hair pegs via interfollicular epidermis was not observed. Coupling also became restricted as follicular cells differentiated to form outer root sheath, inner root sheath, and hair shaft. Extensive gap junctional coupling is characteristic of keratinocytes that are rapidly proliferating (as in hair pegs and germinative matrix). Follicular keratinocytes commence differentiation shortly before restriction of gap junctional coupling becomes evident. Dermal mesenchymal cells undergoing different modes of differentiation also exhibit differences in gap junctional coupling, as evidenced by poor transfer of LY-CH between cells in dermal condensations of hair follicles compared with extensive transfer elsewhere in the dermis. LY-CH and NB were not transferred between epidermal or follicular epithelium and mesenchyme, arguing against a direct role for gap junctions permeable to known second messenger molecules or nucleotides in epithelial-mesenchymal interactions in this system. The distribution of connexins 26 and 43 in epidermis and hair follicles changed during differentiation but there was no correlation with changing patterns of dye transfer, indicating an unexpected degree of complexity in the relationship between gap junctional intercellular communication and connexin protein distribution during development.

  20. Stem cells in the hair follicle bulge contribute to wound repair but not to homeostasis of the epidermis.

    PubMed

    Ito, Mayumi; Liu, Yaping; Yang, Zaixin; Nguyen, Jane; Liang, Fan; Morris, Rebecca J; Cotsarelis, George

    2005-12-01

    The discovery of long-lived epithelial stem cells in the bulge region of the hair follicle led to the hypothesis that epidermal renewal and epidermal repair after wounding both depend on these cells. To determine whether bulge cells are necessary for epidermal renewal, here we have ablated these cells by targeting them with a suicide gene encoding herpes simplex virus thymidine kinase (HSV-TK) using a Keratin 1-15 (Krt1-15) promoter. We show that ablation leads to complete loss of hair follicles but survival of the epidermis. Through fate-mapping experiments, we find that stem cells in the hair follicle bulge do not normally contribute cells to the epidermis which is organized into epidermal proliferative units, as previously predicted. After epidermal injury, however, cells from the bulge are recruited into the epidermis and migrate in a linear manner toward the center of the wound, ultimately forming a marked radial pattern. Notably, although the bulge-derived cells acquire an epidermal phenotype, most are eliminated from the epidermis over several weeks, indicating that bulge stem cells respond rapidly to epidermal wounding by generating short-lived 'transient amplifying' cells responsible for acute wound repair. Our findings have implications for both gene therapy and developing treatments for wounds because it will be necessary to consider epidermal and hair follicle stem cells as distinct populations.

  1. Ingrowing Hair

    PubMed Central

    Luo, Di-Qing; Liang, Yu-Hua; Li, Xi-Qing; Zhao, Yu-Kun; Wang, Fang; Sarkar, Rashmi

    2016-01-01

    Abstract Cutaneous pili migrans and creeping eruption caused by parasitic diseases may present as a moving linear lesion in skin. The former, caused by a hair shaft or fragment embedded in the superficial skin or middle dermis, is a rare condition characterized by creeping eruption with a black line observed at the advancing end. In exceptionally rare instance, the hair grows inside the skin and burrows in the uppermost dermis, such a condition has been called “ingrown hair.” We report a 30-year-old Chinese man, who was accustomed to pull or extrude the beard hairs, with 1-year history of slowly extending black linear eruption on his right chin. Cutaneous examination revealed a 4-cm long black linear lesion beneath the skin associated with edematous erythema around and folliculitis on both ends of the lesion. After treatment with topical mupirocin ointment, the erythema and folliculitis improved and 2 hairs of the beard with hair follicles were pulled out from the skin. Two weeks later, another similar black line about 1 cm in length in the skin presented on the prior lesional area, which was pulled out by a shallow incision of the skin and was also demonstrated as a beard hair with hair follicle. The patient was diagnosed as “ingrowing hair” with multiple recurrences. The lesions recovered after the beard hairs were pulled out. No recurrence occurred in a year of follow-up. We suggest that “ingrowing hair” is better than “ingrown hair” to describe such a condition. Pulling out the involved hair and correcting the bad practice are its optimal management strategies. PMID:27175694

  2. Skin and hair changes during pregnancy

    MedlinePlus

    ... pregnancy; Polymorphic eruption of pregnancy; Melasma - pregnancy; Prenatal skin changes ... during pregnancy may have other effects on your skin. Some women get brownish or yellowish patches around ...

  3. Site-Specific Differentiation of Fibroblasts in Normal and Scleroderma Skin

    DTIC Science & Technology

    2008-06-01

    diversity in its structure and function across anatomic sites. Scalp skin is easily recognizable by the numerous terminal hair follicles ; in contrast...forming the placodes that are progeni- tors of hair follicles (Millar, 2002). Classic heterotopic recombination PERSPECTIVE 776 Journal of...to the development of scales rather than feathers (Dhouailly, 1973, 1984). Specialized fibroblasts from the dermal papilla of hair follicles (Jahoda

  4. Trps1 and its target gene Sox9 regulate epithelial proliferation in the developing hair follicle and are associated with hypertrichosis.

    PubMed

    Fantauzzo, Katherine A; Kurban, Mazen; Levy, Brynn; Christiano, Angela M

    2012-01-01

    Hereditary hypertrichoses are a group of hair overgrowth syndromes that are extremely rare in humans. We have previously demonstrated that a position effect on TRPS1 is associated with hypertrichosis in humans and mice. To gain insight into the functional role of Trps1, we analyzed the late morphogenesis vibrissae phenotype of Trps1(Δgt) mutant mice, which is characterized by follicle degeneration after peg downgrowth has been initiated. We found that Trps1 directly represses expression of the hair follicle stem cell regulator Sox9 to control proliferation of the follicle epithelium. Furthermore, we identified a copy number variation upstream of SOX9 in a family with hypertrichosis that significantly decreases expression of the gene in the hair follicle, providing new insights into the long-range regulation of SOX9. Our findings uncover a novel transcriptional hierarchy that regulates epithelial proliferation in the developing hair follicle and contributes to the pathology of hypertrichosis.

  5. Macrophages induce AKT/β-catenin-dependent Lgr5+ stem cell activation and hair follicle regeneration through TNF

    PubMed Central

    Wang, Xusheng; Chen, Haiyan; Tian, Ruiyun; Zhang, Yiling; Drutskaya, Marina S.; Wang, Chengmei; Ge, Jianfeng; Fan, Zhimeng; Kong, Deqiang; Wang, Xiaoxiao; Cai, Ting; Zhou, Ying; Wang, Jingwen; Wang, Jinmei; Wang, Shan; Qin, Zhihai; Jia, Huanhuan; Wu, Yue; Liu, Jia; Nedospasov, Sergei A.; Tredget, Edward E.; Lin, Mei; Liu, Jianjun; Jiang, Yuyang; Wu, Yaojiong

    2017-01-01

    Skin stem cells can regenerate epidermal appendages; however, hair follicles (HF) lost as a result of injury are barely regenerated. Here we show that macrophages in wounds activate HF stem cells, leading to telogen–anagen transition (TAT) around the wound and de novo HF regeneration, mostly through TNF signalling. Both TNF knockout and overexpression attenuate HF neogenesis in wounds, suggesting dose-dependent induction of HF neogenesis by TNF, which is consistent with TNF-induced AKT signalling in epidermal stem cells in vitro. TNF-induced β-catenin accumulation is dependent on AKT but not Wnt signalling. Inhibition of PI3K/AKT blocks depilation-induced HF TAT. Notably, Pten loss in Lgr5+ HF stem cells results in HF TAT independent of injury and promotes HF neogenesis after wounding. Thus, our results suggest that macrophage-TNF-induced AKT/β-catenin signalling in Lgr5+ HF stem cells has a crucial role in promoting HF cycling and neogenesis after wounding. PMID:28345588

  6. A Study of Noncultured Extracted Hair Follicle Outer Root Sheath Cell Suspension for Transplantation in Vitiligo

    PubMed Central

    Shah, Aarti N; Marfatia, Ritu K; Saikia, Siddhartha S

    2016-01-01

    Context: Vitiligo surgeries have come a long way from tissue grafts to cultured and non cultured cell transplantation. Extracted hair follicle outer root sheath cell transplantation (EHF ORS) suspension is more enriched with melanocyte. In a hair bulb, there is one melanocyte for every five keratinocytes which is much higher than the epidermal melanin unit. Aims: To analyse the effectiveness of cultured EHF ORS and to perform objective evaluation based on clinical improvement & photographic evidence. To observe any untoward events or side effects. Settings and Design: The study was open and uncontrolled. All the patients were screened at preliminary visit. Reviews were done every two weeks. The endpoint selected was six months post procedure. Materials and Methods: Twenty five patients of stable Vitiligo were included in the study and follicular unit were harvested by Follicular Unit Extraction method. Outer root sheath cells were extracted by trypsinization. The solution was transplanted over dermabraded recipient site. Pressure dressing was given. Patients were followed up regularly. Statistical Analysis Used: Descriptive Statistics, Chi-Square. Results: Mean ± SD repigmentation was 80.15% ± 22.9% with excellent repigmentation (90-100%) in 60% of patients. Conclusions: This method is safe, effective, and simpler than the other methods involving cell culturing and requiring a laboratory set-up but selection of patients is crucial for the success of the outcome. PMID:27601859

  7. Gene expression in sheep skin and wool (hair).

    PubMed

    Adelson, D L; Cam, G R; DeSilva, U; Franklin, I R

    2004-01-01

    We sequenced 2939 ESTs from fetal and adult sheep skin. Stages of gestation were picked to coincide with the major events in skin appendage (wool follicle) formation. Clustering analysis generated a nonredundant set of ESTs 2435 strong (83% nonredundant). Approximately 24% of these gave no hit to NCBI build 29 of the human genome, while 35% were tentatively classified by putative function based on BLASTX hits with a p(N) of <10(-4). In addition to bioinformatics analysis of our ESTs and gene mapping, we have generated a large EST spatial expression data set using in situ hybridization. One thousand one hundred forty-two ESTs have been used for in situ localization; about 31% are from adult sheep skin, 39% from late gestation fetal sheep skin, and 30% from midgestation fetal sheep skin. These probes have been used in over 3000 hybridization experiments. In this report, we summarize the results of in situs on adult sheep skin.

  8. Comparison of Alexandrite and Diode Lasers for Hair Removal in Dark and Medium Skin: Which is Better?

    PubMed Central

    Mustafa, Farhad Hamad; Jaafar, Mohamad Suhimi; Ismail, Asaad Hamid; Mutter, Kussay Nugamesh

    2014-01-01

    Introduction: To improve laser hair removal (LHR) for dark skin, the fluence rate reaching the hair follicle in LHR is important. This paper presents the results of a comparative study examining the function of wavelength on dark skin types using 755 nm alexandrite and 810 nm diode lasers. Methods: The structure of the skin was created using a realistic skin model by the Advanced Systems Analysis Program. Result: In this study, the alexandrite laser (755 nm) and diode laser (810 nm) beam–skin tissue interactions were simulated. The simulation results for both lasers differed. The transmission ratio of the diode laser to the dark skin dermis was approximately 4% more than that of the alexandrite laser for the same skin type. For the diode laser at skin depth z = 0.67 mm, the average transmission ratios of both samples were 36% and 27.5%, but those for the alexandrite laser at the same skin depth were 32% and 25%. Conclusion: Both lasers were suitable in LHR for dark skin types, but the diode laser was better than the alexandrite laser because the former could penetrate deeper into the dermis layer. PMID:25653820

  9. Skin academy: hair, skin, hormones and menopause - current status/knowledge on the management of hair disorders in menopausal women.

    PubMed

    Blume-Peytavi, Ulrike; Atkin, Stephen; Gieler, Uwe; Grimalt, Ramon

    2012-01-01

    Menopause is defined by 12 months of amenorrhea after the final menstrual period. The reduction in ovarian hormones and increased androgen levels can manifest as hair and skin disorders. Although hirsutism, unwanted facial hair, alopecia, skin atrophy and slackness of facial skin are common issues encountered by post-menopausal women, these problems receive very little attention relative to other menopausal symptoms. The visibility of these disorders has been shown to cause significant anxiety and may impact on patients' self-esteem and quality of life, particularly given the strong association of hair and skin with a woman's femininity and beauty, which is demonstrated by extensive marketing by the cosmetic industry targeting this population and the large expenditure on these products by menopausal women. The proportion of the female population who are in the post-menopausal age group is rising. Therefore, the prevalence of these dermatological symptoms is likely to increase. Current therapies aim to rectify underlying hormonal imbalances and improve cosmetic appearance. However, there is little evidence to support treatment for these disorders specifically in post-menopausal women. This review discusses the assessment and treatment of both the physiological and psychological aspects of hair and skin disorders pertinent to the growing post-menopausal population.

  10. A rapid screening method using DNA binding dyes to determine whether hair follicles have sufficient DNA for successful profiling.

    PubMed

    Haines, Alicia M; Linacre, Adrian

    2016-05-01

    We report a simple screening method to assess the viability of successful DNA profiling from single hair follicles. A total of 48 hair samples (shed and plucked) were collected from male and female donors and the root tips (0.5cm) were stained using one of three DNA binding dyes (EvaGreen™, Diamond™ Nucleic Acid Dye and RedSafe™) at 20× concentration. The hairs were subsequently viewed under a Nikon Optiphot fluorescent microscope to count the approximate number of nuclei in one plane of view. The hairs were then processed using either (1) a DNA extraction kit (QIAmp(®) Mini Kit) and then amplified using the AmpFLSTR(®) NGM™ kit, which amplifies 15 short tandem repeat (STR) loci plus the gender marker amelogenin, or (2) by direct PCR amplification using the same DNA profiling kit. Diamond™ dye had the lowest background signal and plucked hairs treated with this dye produced full DNA profiles when amplified directly and was chosen to screen a further 150 mixed hair samples. These hairs were separated into one of five categories (1, >100 nuclei; 1.5, 50-99 nuclei; 2, 1-49 nuclei; 2.5, no nuclei but high fluorescent signal; 3, no nuclei and very low fluorescent signal) from which 60 of the hairs were chosen to undergo direct amplification using the NGM™ kit. It was found that there was a direct correlation to the category designation and the ability to obtain a DNA profile up-loadable to the Australian DNA Database. Approximately 91% of category 1 hairs resulted in either a full or high partial (12-29 alleles) profile by direct PCR whereas about 78% of category 3 hairs exhibited no amplification. The results show that this method can be used to predict successful STR amplification from single hair follicles. It is a rapid, sensitive, cheap, non-destructive and easy to perform methodology applicable for screening multiple hairs in order to aid forensic investigators in predicting hairs that will yield DNA results.

  11. Comparison of nestin-expressing multipotent stem cells in the tongue fungiform papilla and vibrissa hair follicle.

    PubMed

    Mii, Sumiyuki; Amoh, Yasuyuki; Katsuoka, Kensei; Hoffman, Robert M

    2014-06-01

    We have previously reported that hair follicles contain multipotent stem cells, which express nestin and participate in follicle growth at anagen as well as in the extension of the follicle sensory nerve. The nestin-driven green fluorescent protein (ND-GFP) transgenic mouse labels all nestin-expressing cells with GFP. The hair follicle nestin-GFP cells can differentiate into neurons, Schwann cells, and other cell types. In this study, we describe nestin-expressing multipotent stem cells in the fungiform papilla in the tongue. The nestin-expressing multipotent stem cells in the fungiform papilla are located around a peripheral sensory nerve immediately below the taste bud and co-express the neural crest cell marker p75(NTR) . The fungiform papilla cells formed spheres in suspension culture in DMEM-F12 medium supplemented with basic fibroblast growth factor (bFGF). The spheres consisted of nestin-expressing cells that co-expressed the neural crest marker p75(NTR) and which developed expression of the stem cell marker CD34. P75(NTR), CD34 and nestin co-expression suggested that nestin-expressing cells comprising the fungiform papilla spheres were in a relatively undifferentiated state. The nestin-expressing cells of these spheres acquired the following markers: β III tubulin typical of nerve cells; GFAP typical of glial cells; K15 typical of keratinocytes; and smooth-muscle antigen (SMA), after transfer to RPMI 1640 medium with 10% fetal bovine serum (FBS), suggesting they differentiated into multiple cell types. The results of the current study indicate nestin-expressing fungiform papilla cells and the nestin-expressing hair follicle stem cells have common features of cell morphology and ability to differentiate into multiple cell types, suggesting their remarkable similarity.

  12. Ginsenoside Rg3 up-regulates the expression of vascular endothelial growth factor in human dermal papilla cells and mouse hair follicles.

    PubMed

    Shin, Dae Hyun; Cha, Youn Jeong; Yang, Kyeong Eun; Jang, Ik-Soon; Son, Chang-Gue; Kim, Bo Hyeon; Kim, Jung Min

    2014-07-01

    Crude Panax ginseng has been documented to possess hair growth activity and is widely used to treat alopecia, but the effects of ginsenoside Rg3 on hair growth have not to our knowledge been determined. The aim of the current study was to identify the molecules through which Rg3 stimulates hair growth. The thymidine incorporation for measuring cell proliferation was determined. We used DNA microarray analysis to measure gene expression levels in dermal papilla (DP) cells upon treatment with Rg3. The mRNA and protein expression levels of vascular endothelial growth factor (VEGF) in human DP cells were measured by real-time polymerase chain reaction and immunohistochemistry, respectively. We also used immunohistochemistry assays to detect in vivo changes in VEGF and 3-stemness marker expressions in mouse hair follicles. Reverse transcription polymerase chain reaction showed dose-dependent increases in VEGF mRNA levels on treatment with Rg3. Immunohistochemical analysis showed that expression of VEGF was significantly up-regulated by Rg3 in a dose-dependent manner in human DP cells and in mouse hair follicles. In addition, the CD8 and CD34 were also up-regulated by Rg3 in the mouse hair follicles. It may be concluded that Rg3 might increase hair growth through stimulation of hair follicle stem cells and it has the potential to be used in hair growth products.

  13. The size of sebaceous glands in relation to the size of hair follicles on the heads of some small mammals (Insectivora, Chiroptera, Rodentia).

    PubMed

    Haffner, M

    1998-04-01

    Many large sebaceous glands have been described, and functions such as scent production suggested, but gland size has seldom been studied in relation to the surface area of their hair follicles. However, investigating this relationship is essential for establishing whether glands produce more sebum than would be required for lubricating associated hair alone. Here, the relationship between sebaceous gland size and the surface area of the associated hair follicles has been studied. Glands on the heads of 20 species from three orders were compared with those associated with fur hairs. In all species, the fur hairs had small hair follicles with small sebaceous glands, as had the mystacial and submandibular hairs of Rodentia. Medium-sized glands and hairs were found in the mystacial and submandibular region in Insectivora, and in the circumoral region in Chiroptera and Rodentia. Large glands and hairs were found on a pad in the corner of the mouth in Rodentia. Although the size of glands was not directly proportional to hair size, some gross trends were noted. Vibrissae had either no or very small sebaceous glands. It is likely that sebum has to be provided from elsewhere to lubricate their surfaces. The glands on the snout of Insectivora and Chiroptera are clearly enlarged and could probably produce more sebum than would be required for grooming vibrissae alone. In Rodentia, vibrissae were surrounded by small hair and glands, and the nearest glands large enough to provide sebum were the glands on the pad in the mouth corner.

  14. Fluorescence lifetime imaging of human skin and hair

    NASA Astrophysics Data System (ADS)

    Ehlers, A.; Riemann, I.; Anhut, T.; Kaatz, M.; Elsner, P.; König, K.

    2006-02-01

    Multiphoton imaging has developed into an important technique for in-vivo research in life sciences. With the laser System DermaInspect (JenLab, Germany) laser radiation from a Ti:Sapphire laser is used to generate multiphotonabsorption deep in the human skin in vivo. The resulting autofluorescence radiation arises from endogenous fluorophores such as NAD(P)H, flavines, collagen, elastin, porphyrins und melanin. Second harmonic generation (SHG) was used to detect collagen structures in the dermal layer. Femtosecond laser multiphoton imaging offers the possibility of high resolution optical tomography of human skin as well as fluorescence lifetime imaging (FLIM) with picosecond time resolution. In this work a photon detector with ultrashort rise time of less than 30ps was applied to FLIM measurements of human skin and hair with different pigmentation. Fluorescence lifetime images of different human hair types will be discussed.

  15. Electrophysiological property and chemical sensitivity of primary afferent neurons that innervate rat whisker hair follicles

    PubMed Central

    Ikeda, Ryo

    2016-01-01

    Whisker hair follicles are sensory organs that sense touch and perform tactile discrimination in animals, and they are sites where sensory impulses are initiated when whisker hairs touch an object. The sensory signals are then conveyed by whisker afferent fibers to the brain for sensory perception. Electrophysiological property and chemical sensitivity of whisker afferent fibers, important factors affecting whisker sensory processing, are largely not known. In the present study, we performed patch-clamp recordings from pre-identified whisker afferent neurons in whole-mount trigeminal ganglion preparations and characterized their electrophysiological property and sensitivity to ATP, serotonin and glutamate. Of 97 whisker afferent neurons examined, 67% of them are found to be large-sized (diameter ≥45 µm) cells and 33% of them are medium- to small-sized (diameter <45 µm) cells. Almost every large-sized whisker afferent neuron fires a single action potential but many (40%) small/medium-sized whisker afferent neurons fire multiple action potentials in response to prolonged stepwise depolarization. Other electrophysiological properties including resting membrane potential, action potential threshold, and membrane input resistance are also significantly different between large-sized and small/medium-sized whisker afferent neurons. Most large-sized and many small/medium-sized whisker afferent neurons are sensitive to ATP and/or serotonin, and ATP and/or serotonin could evoke strong inward currents in these cells. In contrast, few whisker afferent neurons are sensitive to glutamate. Our results raise a possibility that ATP and/or serotonin may be chemical messengers involving sensory signaling for different types of rat whisker afferent fibers. PMID:27927797

  16. Aging of hair.

    PubMed

    Trüeb, Ralph M

    2005-06-01

    The appearance of hair plays an important role in people's overall physical appearance and self-perception. With today's increasing life expectation, the desire to look youthful plays a bigger role than ever. The hair care industry has become aware of this and also more capable to deliver active products that are directed toward meeting this consumer demand. The discovery of pharmacological targets and the development of safe and effective drugs also indicate strategies of the drug industry for maintenance of healthy and beautiful hair. Hair aging comprises weathering of the hair shaft and aging of the hair follicle. The latter manifests as decrease of melanocyte function or graying, and decrease in hair production in androgenetic and senescent alopecia. The scalp is also subject to intrinsic or physiologic aging and extrinsic aging caused by external factors. Intrinsic factors are related to individual genetic and epigenetic mechanisms with interindividual variation. Prototypes are familial premature graying and androgenetic alopecia. Extrinsic factors include ultraviolet radiation and smoking. Experimental evidence supports the hypothesis that oxidative stress plays a role in skin and hair aging. Topical anti-aging compounds for hair include humefactants, hair conditioners, photoprotectors, and antioxidants. Current available treatment modalities with proven efficacy for treatment of androgenetic alopecia are topical minoxidil, oral finasteride, and autologous hair transplantation. In the absence of another way to reverse hair graying, hair colorants are the mainstays of recovering lost hair color. Topical liposome targeting for melanins, genes, and proteins selectively to hair follicles are under current investigation.

  17. Activated hair follicle stem cells and Wnt/β-catenin signaling involve in pathnogenesis of sebaceous neoplasms.

    PubMed

    Qiu, Weiming; Lei, Mingxing; Li, Jin; Wang, Ning; Lian, Xiaohua

    2014-01-01

    Sebaceous glands (SGs) undergo cyclic renewal independent of hair follicle stem cells (HFSCs) activation while HFSCs have the potential to differentiate into sebaceous gland cells, hair follicle and epidermal keratinocytes. Abnormalities of sebaceous gland progenitor cells contribute to the development of sebaceous neoplasms, but little is known about the role of HFSCs during sebaceous neoplasm development. Here, using dimethylbenzanthracene (DMBA) plus 12-o-tetradecanoyl phorbol-13-acetate (TPA) treatment developing sebaceous neoplasms (SNs) were identified with H&E and Oil red O staining. And then the molecular expression and activation of HFSCs and was characterized by immunostaining. Wnt10b/β-catenin signaling molecular which is important for activation of HFSCs were detected by immunostaining. We found hair follicle and epidermal cell markers were expressed in sebaceous neoplasms. Furthermore, SOX-9 and CD34-positive HFSCs were located in the basal layer of sebaceous lobules within the sebaceous neoplasms. Many appear to be in an active state. Finally, Wnt10b/β-catenin signaling was activated within the basal cells of sebaceous lobules in the sebaceous neoplasms. Collectively, our findings suggest that the abnormal activation of both HFSCs and Wnt10b/β-catenin signaling involves in the development of sebaceous neoplasms.

  18. Reciprocal requirements for Eda/Edar/NF-κB and Wnt/β-catenin signaling pathways in hair follicle induction

    PubMed Central

    Zhang, Yuhang; Tomann, Philip; Andl, Thomas; Gallant, Natalie M.; Huelsken, Joerg; Jerchow, Boris; Birchmeier, Walter; Paus, Ralf; Piccolo, Stefano; Mikkola, Marja L.; Morrisey, Edward E.; Overbeek, Paul A.; Scheidereit, Claus; Millar, Sarah E.; Schmidt-Ullrich, Ruth

    2009-01-01

    SUMMARY Wnt/β-catenin and NF-κB signaling mechanisms provide central controls in development and disease, but how these pathways intersect is unclear. Using hair follicle induction as a model system, we show that patterning of dermal Wnt/β-catenin signaling requires epithelial β-catenin activity. We find that Wnt/β-catenin signaling is absolutely required for NF-κB activation, and that Edar is a direct Wnt target gene. Wnt/β-catenin signaling is initially activated independently of Eda/Edar/NF-κB activity in primary hair follicle primordia. However, Eda/Edar/NF-κB signaling is required to refine the pattern of Wnt/β-catenin activity, and to maintain this activity at later stages of placode development. We show that maintenance of localized expression of Wnt10b and Wnt10a requires NF-κB signaling, providing a molecular explanation for the latter observation, and identify Wnt10b as a direct NF-κB target. These data reveal a complex interplay and inter-dependence of Wnt/β-catenin and Eda/Edar/NF-κB signaling pathways in initiation and maintenance of primary hair follicle placodes. PMID:19619491

  19. Transdifferentiation of Human Hair Follicle Mesenchymal Stem Cells into Red Blood Cells by OCT4.

    PubMed

    Liu, Zhijing; Lu, Shi-Jiang; Lu, Yan; Tan, Xiaohua; Zhang, Xiaowei; Yang, Minlan; Zhang, Fuming; Li, Yulin; Quan, Chengshi

    2015-01-01

    Shortage of red blood cells (RBCs, erythrocytes) can have potentially life-threatening consequences for rare or unusual blood type patients with massive blood loss resulting from various conditions. Erythrocytes have been derived from human pluripotent stem cells (PSCs), but the risk of potential tumorigenicity cannot be ignored, and a majority of these cells produced from PSCs express embryonic ε- and fetal γ-globins with little or no adult β-globin and remain nucleated. Here we report a method to generate erythrocytes from human hair follicle mesenchymal stem cells (hHFMSCs) by enforcing OCT4 gene expression and cytokine stimulation. Cells generated from hHFMSCs expressed mainly the adult β-globin chain with minimum level of the fetal γ-globin chain. Furthermore, these cells also underwent multiple maturation events and formed enucleated erythrocytes with a biconcave disc shape. Gene expression analyses showed that OCT4 regulated the expression of genes associated with both pluripotency and erythroid development during hHFMSC transdifferentiation toward erythroid cells. These findings show that mature erythrocytes can be generated from adult somatic cells, which may serve as an alternative source of RBCs for potential autologous transfusion.

  20. The histocompatibility research of hair follicle stem cells with bladder acellular matrix

    PubMed Central

    Li, Jia; Wang, Wenguang; Li, Jiuzhi; Rexiati, Mulati; An, Henqing; Wang, Feng; Wang, Yujie

    2016-01-01

    Abstract Background: Hair follicle stem cells (HFSCs) were reported to have multidirectional differentiation ability and could be differentiated into melanocytes, keratin cells, smooth muscle cells, and neurons. However, the functionality of HFSCs in bladder tissue regeneration is unknown. Methods: This study was conducted to build HFSCs vs bladder acellular matrix (BAM) complexes (HFSCs–BAM complexes) in vitro and evaluated whether HFSCs have well biocompatibility with BAM. HFSCs were separated from SD rats. BAM scaffold was prepared from the submucosa of rabbit bladder tissue. Afterwards, HFSCs were inoculated on BAM. Results: HFSCs–BAM complexes grew rapidly through inverted microscope observation. Cell growth curve showed the proliferation was in stagnate phase at 7th and 8th day. Cytotoxicity assay showed the toxicity grading of BAM was 0 or 1. Scanning electron microscopy, HE staining, and masson staining showed that cells have germinated on the surface of scaffold. Conclusion: The results provide evidence that HFSCs–BAM complexes have well biocompatibility and accumulate important experimental basis for clinical applying of tissue engineering bladder. PMID:27828841

  1. Adult interfollicular tumour-initiating cells are reprogrammed into an embryonic hair follicle progenitor-like fate during basal cell carcinoma initiation.

    PubMed

    Youssef, Khalil Kass; Lapouge, Gaëlle; Bouvrée, Karine; Rorive, Sandrine; Brohée, Sylvain; Appelstein, Ornella; Larsimont, Jean-Christophe; Sukumaran, Vijayakumar; Van de Sande, Bram; Pucci, Doriana; Dekoninck, Sophie; Berthe, Jean-Valery; Aerts, Stein; Salmon, Isabelle; del Marmol, Véronique; Blanpain, Cédric

    2012-12-01

    Basal cell carcinoma, the most frequent human skin cancer, arises from activating hedgehog (HH) pathway mutations; however, little is known about the temporal changes that occur in tumour-initiating cells from the first oncogenic hit to the development of invasive cancer. Using an inducible mouse model enabling the expression of a constitutively active Smoothened mutant (SmoM2) in the adult epidermis, we carried out transcriptional profiling of SmoM2-expressing cells at different times during cancer initiation. We found that tumour-initiating cells are massively reprogrammed into a fate resembling that of embryonic hair follicle progenitors (EHFPs). Wnt/ β-catenin signalling was very rapidly activated following SmoM2 expression in adult epidermis and coincided with the expression of EHFP markers. Deletion of β-catenin in adult SmoM2-expressing cells prevents EHFP reprogramming and tumour initiation. Finally, human basal cell carcinomas also express genes of the Wnt signalling and EHFP signatures.

  2. Biochemical and ultrastructural processing of (/sup 125/I)epidermal growth factor in rat epidermis and hair follicles: accumulation of nuclear label

    SciTech Connect

    Green, M.R.; Mycock, C.; Smith, C.G.; Couchman, J.R.

    1987-03-01

    Although the intracellular ultrastructural processing of epidermal growth factor (EGF) and its receptor have been described in cell culture systems, very few studies have examined this phenomenon in intact tissues. We have examined the ultrastructural and biochemical handling of (/sup 125/I)EGF in the epidermis and hair follicle bulb of intact, viable, 3- to 5-day-old rat skin the EGF receptor distribution of which has already been documented and in which EGF has been shown to be biologically active. After incubation of explants with 10 nM (/sup 125/I)EGF for 2.5 h at 25 degrees or 37 degrees C, radiolabel was detected over the basal cells of the epidermis and hair follicle outer root sheath, confirming previous light microscope observations. More specifically, silver grains were observed near coated and uncoated plasma membrane and coated membrane invaginations, Golgi apparatus, lysosomal structures, and nuclei. Sodium azide inhibited internalization of label, whereas a series of lysosomal inhibitors (chloroquine, monensin, and iodoacetamide) caused a slight increase in silver grains associated with lysosomal vesicles and a decrease in nuclear label. Biochemical analysis indicated that greater than 35% of radioactivity following incubation at 37 degrees C was in the form of degraded (/sup 125/I)EGF fragments and that inclusion of chloroquine, monensin, and iodoacetamide reduced this value to 20.8%, 8.6%, and 4.0%, respectively. In addition, chloramine T-prepared (/sup 125/I)EGF was found to be covalently cross-linked with low efficiency to a protein having the molecular weight of the EGF receptor. These data are discussed in the light of the effects of EGF on epithelial cell proliferation in skin.

  3. Acidic and basic hair/nail ("hard") keratins: their colocalization in upper cortical and cuticle cells of the human hair follicle and their relationship to "soft" keratins

    PubMed Central

    1986-01-01

    Although numerous hair proteins have been studied biochemically and many have been sequenced, relatively little is known about their in situ distribution and differential expression in the hair follicle. To study this problem, we have prepared several mouse monoclonal antibodies that recognize different classes of human hair proteins. Our AE14 antibody recognizes a group of 10-25K hair proteins which most likely corresponds to the high sulfur proteins, our AE12 and AE13 antibodies define a doublet of 44K/46K proteins which are relatively acidic and correspond to the type I low sulfur keratins, and our previously described AE3 antibody recognizes a triplet of 56K/59K/60K proteins which are relatively basic and correspond to the type II low sulfur keratins. Using these and other immunological probes, we demonstrate the following. The acidic 44K/46K and basic 56-60K hair keratins appear coordinately in upper corticle and cuticle cells. The 10-25K, AE14-reactive antigens are expressed only later in more matured corticle cells that are in the upper elongation zone, but these antigens are absent from cuticle cells. The 10-nm filaments of the inner root sheath cells fail to react with any of our monoclonal antibodies and are therefore immunologically distinguishable from the cortex and cuticle filaments. Nail plate contains 10-20% soft keratins in addition to large amounts of hair keratins; these soft keratins have been identified as the 50K/58K and 48K/56K keratin pairs. Taken together, these results suggest that the precursor cells of hair cortex and nail plate share a major pathway of epithelial differentiation, and that the acidic 44K/46K and basic 56-60K hard keratins represent a co- expressed keratin pair which can serve as a marker for hair/nail-type epithelial differentiation. PMID:2432071

  4. In situ patch-clamp recordings from Merkel cells in rat whisker hair follicles, an experimental protocol for studying tactile transduction in tactile-end organs.

    PubMed

    Ikeda, Ryo; Ling, Jennifer; Cha, Myeounghoon; Gu, Jianguo G

    2015-04-25

    Mammals use tactile end-organs to perform sensory tasks such as environmental exploration, social interaction, and tactile discrimination. However, cellular and molecular mechanisms underlying tactile transduction in tactile end-organs remain poorly understood. The patch-clamp recording technique may be the most valuable approach for detecting and studying tactile transduction in tactile end-organs, but it is technically challenging because tactile transduction elements in an end-organ are normally inaccessible by patch-clamp recording electrodes. Here we describe an in situ patch-clamp recording protocol for the study of tactile transduction in Merkel cells of rat whisker hair follicles, one of the most sensitive tactile end-organs in mammals. This technique offers an opportunity to explore the identities and properties of ion channels that are involved in tactile transduction in whisker hair follicles, and it may also lend a useful tool for researchers to study other tactile end-organs. The experimental protocol describes procedures for 1) tissue dissection and whisker hair follicle preparation, 2) device setup and steps for performing patch-clamp recordings from Merkel cells in a whisker hair follicle, 3) methods of delivering mechanical stimuli, and 4) intra-follicle microinjection for receptor knockdown in whisker hair follicles. The main procedures in this protocol, from tissue preparation to whole-cell patch-clamp recordings, can be completed in a few hours.

  5. Investigation of Hair Follicle and Plasma Biomarkers for Low-Level VX Vapor Exposure

    DTIC Science & Technology

    2006-11-01

    Hair Tutudak e Hair Analysis: Villian, M.; Cirimele, V.; Kintz, P. Hair Analysis in Yamazak Associated Glycoproteins Tyrosinase , TRP-1, and TRP-2...Ogawa, H. Hair Cycle-Dependent Expression of Hepatocyte-Growth Factor (HGF) Activator, Other Proteinases, AND Proteinase Inhibitors Correlates with

  6. Laser hair removal.

    PubMed

    Ibrahimi, Omar A; Avram, Mathew M; Hanke, C William; Kilmer, Suzanne L; Anderson, R Rox

    2011-01-01

    The extended theory of selective photothermolysis enables the laser surgeon to target and destroy hair follicles, thereby leading to hair removal. Today, laser hair removal (LHR) is the most commonly requested cosmetic procedure in the world and is routinely performed by dermatologists, other physicians, and non-physician personnel with variable efficacy. The ideal candidate for LHR is fair skinned with dark terminal hair; however, LHR can today be successfully performed in all skin types. Knowledge of hair follicle anatomy and physiology, proper patient selection and preoperative preparation, principles of laser safety, familiarity with the various laser/light devices, and a thorough understanding of laser-tissue interactions are vital to optimizing treatment efficacy while minimizing complications and side effects.

  7. Microfluidic Isolation of CD34-Positive Skin Cells Enables Regeneration of Hair and Sebaceous Glands In Vivo

    PubMed Central

    Zhu, Beili; Nahmias, Yaakov; Yarmush, Martin L.

    2014-01-01

    Skin stem cells resident in the bulge area of hair follicles and at the basal layer of the epidermis are multipotent and able to self-renew when transplanted into full-thickness defects in nude mice. Based on cell surface markers such as CD34 and the α6-integrin, skin stem cells can be extracted from tissue-derived cell suspensions for engraftment using the gold standard cell separation technique of fluorescence-activated cell sorting (FACS). This paper describes an alternative separation method using microfluidic devices coated with degradable antibody-functionalized hydrogels. The microfluidic method allows direct injection of tissue digestate (no preprocessing tagging of cells is needed), is fast (45 minutes from injected sample to purified cells), and scalable. This method is used in this study to isolate CD34-positive (CD34+) cells from murine skin tissue digestate, and the functional capability of these cells is demonstrated by transplantation into nude mice using protocols developed by other groups for FACS-sorted cells. Specifically, the transplantation of microfluidic isolated CD34+ cells along with dermal and epidermal cells was observed to generate significant levels of hair follicles and sebaceous glands consistent with those observed previously with FACS-sorted cells. PMID:25205844

  8. Quantification of nanoparticle uptake into hair follicles in pig ear and human forearm.

    PubMed

    Raber, A S; Mittal, A; Schäfer, J; Bakowsky, U; Reichrath, J; Vogt, T; Schaefer, U F; Hansen, S; Lehr, C-M

    2014-04-10

    Drug delivery via the hair follicle (HF) especially with nanoparticles (NP) recently gained attention due to a depot effect and facilitated absorption conditions within the lower HF. With the prospect of transdermal drug delivery, it is of interest to optimize the follicular uptake of NP. In this study, a method was developed to quantify NP uptake into HF and applied in vitro in a pig ear model and in vivo in human volunteers. The influence of NP material on HF uptake was investigated using fluorescence-labeled NP based on poly(D,L-lactide-co-glycolide) (PLGA). All NP had similar hydrodynamic sizes (163-170 nm) but different surface modifications: (i) plain PLGA, (ii) chitosan-coated PLGA (Chit.-PLGA), and (iii) Chit.-PLGA coated with different phospholipids (PL) (DPPC (100), DPPC:Chol (85:15), and DPPC:DOTAP (92:8). Differential stripping was performed, including complete mass balance. The samples were extracted for fluorescence quantification. An effect of the PL coating on follicular uptake was observed as DPPC (100) and DPPC:DOTAP (92:8) penetrated into HF to a higher extent than the other tested NP. The effect was observed both in the pig ear model as well as in human volunteers, although it was statistically significant only in the in vitro model. An excellent in vitro-in vivo correlation (IVIVC, r(2)=0.987) between both models was demonstrated, further supporting the suitability of the pig ear model as a surrogate for the in vivo situation in humans for quantifying NP uptake into HF. These findings may help to optimize NP for targeting the HF and to improve transdermal delivery.

  9. Hair follicle disruption facilitates pathogenesis to UVB-induced cutaneous inflammation and basal cell carcinoma development in Ptch(+/-) mice.

    PubMed

    Xu, Jianmin; Weng, Zhiping; Arumugam, Aadithya; Tang, Xiuwei; Chaudhary, Sandeep C; Li, Changzhao; Christiano, Angela M; Elmets, Craig A; Bickers, David R; Athar, Mohammad

    2014-05-01

    Hairless mice carrying homozygous mutations in hairless gene manifest rudimentary hair follicles (HFs), epidermal cysts, hairless phenotype, and enhanced susceptibility to squamous cell carcinomas. However, their susceptibility to basal cell carcinomas (BCCs), a neoplasm considered originated from HF-localized stem cells, is unknown. To demonstrate the role of HFs in BCC development, we bred Ptch(+/-)/C57BL6 with SKH-1 hairless mice, followed by brother-sister cross to get F2 homozygous mutant (hairless) or wild-type (haired) mice. UVB-induced inflammation was less pronounced in shaved haired than in hairless mice. In hairless mice, inflammatory infiltrate was found around the rudimentary HFs and epidermal cysts. Expression of epidermal IL1f6, S100a8, vitamin D receptor, repetin, and major histocompatibility complex II, biomarkers depicting susceptibility to cutaneous inflammation, was also higher. In these animals, HF disruption altered susceptibility to UVB-induced BCCs. Tumor onset in hairless mice was 10 weeks earlier than in haired littermates. The incidence of BCCs was significantly higher in hairless than in haired animals; however, the magnitude of sonic hedgehog signaling did not differ significantly. Overall, 100% of hairless mice developed >12 tumors per mouse after 32 weeks of UVB therapy, whereas haired mice developed fewer than three tumors per mouse after 44 weeks of long-term UVB irradiation. Tumors in hairless mice were more aggressive than in haired littermates and manifested decreased E-cadherin and enhanced mesenchymal proteins. These data provide novel evidence that disruption of HFs in Ptch(+/-) mice enhances cutaneous susceptibility to inflammation and BCCs.

  10. Occurrence of Staphylococcus intermedius on the hair and skin of normal dogs.

    PubMed

    Allaker, R P; Lloyd, D H; Simpson, A I

    1992-03-01

    Aerobic bacterial populations were studied on the distal hair coat and at the skin surface of the shoulder, rump and abdomen of 10 healthy dogs. Coagulase negative staphylococci (CNS) were more frequently isolated from the hair than the skin at the shoulder and rump. There was no difference in the isolation rate of coagulase positive staphylococci (CPS) (Staphylococcus intermedius) between the hair and skin. Total skin counts were greatest on the abdomen whereas CNS counts from the hair were least at this site. There were no differences between CPS counts at the three sites on either hair or skin. The populations on the relatively unfavourable microenvironment of the distal hair may represent contamination rather than colonisation. The low populations of CPS at the skin surface also indicate contamination or transient colonisation rather than true resident status.

  11. VEGF induces proliferation of human hair follicle dermal papilla cells through VEGFR-2-mediated activation of ERK

    SciTech Connect

    Li, Wei; Man, Xiao-Yong; Li, Chun-Ming; Chen, Jia-Qi; Zhou, Jiong; Cai, Sui-Qing; Lu, Zhong-Fa; Zheng, Min

    2012-08-15

    Vascular endothelial growth factor (VEGF) is one of the strongest regulators of physiological and pathological angiogenesis. VEGF receptor 2 (VEGFR-2), the primary receptor for VEGF, is thought to mediate major functional effects of VEGF. Previously, we have localized both VEGF and VEGFR-2 in human hair follicles. In this study, we further defined the expression and roles of VEGFR-2 on human hair follicle dermal papilla (DP) cells. The expression of VEGFR-2 on DP cells was examined by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analysis separately, and localization of VEGFR-2 was defined by immunofluorescence. The effect of VEGF on DP cells was analyzed by MTT assays and specific inhibitors. Finally, the role of VEGF involved in the signaling pathways was investigated by Western blot. RT-PCR and Western blot analysis demonstrated the expression of VEGFR-2 on DP cells. Immunostaining for VEGFR-2 showed strong signal on cultured human DP cells in vitro. Exogenous VEGF{sub 165} stimulated proliferation of DP cells in a dose-dependent manner. Furthermore, this stimulation was blocked by a VEGFR-2 neutralizing antibody (MAB3571) and an ERK inhibitor (PD98059). VEGF{sub 165}-induced phosphorylation of ERK1/2 was abolished by MAB3571 and PD98059, while the phosphorylation of p38, JNK and AKT were not changed by VEGF{sub 165}. Taken together, VEGFR-2 is expressed on primary human hair follicle DP cells and VEGF induces proliferation of DP cells through VEGFR-2/ERK pathway, but not p38, JNK or AKT signaling. -- Highlights: Black-Right-Pointing-Pointer We examine the expression of VEGFR-2 on cultured human dermal papilla (DP) cells. Black-Right-Pointing-Pointer VEGF{sub 165} stimulated proliferation of human DP cells in a dose-dependent manner. Black-Right-Pointing-Pointer This stimulation was through VEGFR-2-mediated activation of ERK.

  12. Human hair follicle pluripotent stem (hfPS) cells promote regeneration of peripheral-nerve injury: an advantageous alternative to ES and iPS cells.

    PubMed

    Amoh, Yasuyuki; Kanoh, Maho; Niiyama, Shiro; Hamada, Yuko; Kawahara, Katsumasa; Sato, Yuichi; Hoffman, Robert M; Katsuoka, Kensei

    2009-08-01

    The optimal source of stem cells for regenerative medicine is a major question. Embryonic stem (ES) cells have shown promise for pluripotency but have ethical issues and potential to form teratomas. Pluripotent stem cells have been produced from skin cells by either viral-, plasmid- or transposon-mediated gene transfer. These stem cells have been termed induced pluripotent stem cells or iPS cells. iPS cells may also have malignant potential and are inefficiently produced. Embryonic stem cells may not be suited for individualized therapy, since they can undergo immunologic rejection. To address these fundamental problems, our group is developing hair follicle pluripotent stem (hfPS) cells. Our previous studies have shown that mouse hfPS cells can differentiate to neurons, glial cells in vitro, and other cell types, and can promote nerve and spinal cord regeneration in vivo. hfPS cells are located above the hair follicle bulge in what we have termed the hfPS cell area (hfPSA) and are nestin positive and keratin 15 (K-15) negative. Human hfPS cells can also differentiate into neurons, glia, keratinocytes, smooth muscle cells, and melanocytes in vitro. In the present study, human hfPS cells were transplanted in the severed sciatic nerve of the mouse where they differentiated into glial fibrillary-acidic-protein (GFAP)-positive Schwann cells and promoted the recovery of pre-existing axons, leading to nerve generation. The regenerated nerve recovered function and, upon electrical stimulation, contracted the gastrocnemius muscle. The hfPS cells can be readily isolated from the human scalp, thereby providing an accessible, autologous and safe source of stem cells for regenerative medicine that have important advantages over ES or iPS cells.

  13. Hair Loss (Alopecia)

    MedlinePlus

    ... otherwise healthy people. The disease destroys a person’s hair follicles. Scar tissue forms where the follicles once were, ... tries to stop the inflammation, which destroys the hair follicles. Central centrifugal cicatricial (scarring) alopecia: This type of ...

  14. Utility of saliva and hair follicles in donor selection for hematopoietic stem cell transplantation and chimerism monitoring.

    PubMed

    Kaur, Gurvinder; Kumar, Neeraj; Nandakumar, Ramya; Rapthap, Chowphi C; Sharma, Gaurav; Neolia, Shekhar; Kumra, Heena; Mahalwar, Prateek; Garg, Abhinav; Kumar, Sunil; Kaur, Jasmeet; Hakim, Mrinali; Kumar, Lalit; Mehra, Narinder K

    2012-01-01

    Selection of an HLA identical donor is a critical pre-requisite for successful hematopoietic stem cell transplantation (HSCT). Most transplant centers utilize blood as the most common source of DNA for HLA testing. However, obtaining blood through phlebotomy is often challenging in patients with conditions like severe leucopenia or hemophilia, pediatric and elderly patients. We have used a simple in-house protocol and shown that HLA genotypes obtained on DNA extracted from saliva or hair are concordant with blood and hence can be used for selection of donors for HSCT or organ transplantation. Similarly, for post-HSCT chimerism monitoring, non-availability of pre-transplant DNA samples poses a major limitation of reference STR fingerprints. This study shows that DNA obtained post-HSCT from hair follicles can be used to generate pre-transplant patient specific fingerprints while the STR profiles obtained in saliva samples cannot as these display a mixed state of chimerism.

  15. Successful direct amplification of nuclear markers from a single hair follicle.

    PubMed

    Ottens, Renée; Taylor, Duncan; Abarno, Damien; Linacre, Adrian

    2013-06-01

    We report on successful amplification of DNA profiles from a single hair. Direct amplification was used on the root tip of both anagen and telogen hairs using a kit to amplify 15 STR loci. All 30 anagen hairs tested from five different people gave full DNA profiles after 29 cycles with no allelic drop-in or heterozygous imbalance. Six of the 30 telogen hairs tested resulted in a full DNA profile, and a further four telogen hair samples tested produced a DNA profile of five or more complete loci that could be up-loaded to the National DNA Database (Australia). A full DNA profile was also obtained from the shaft of an anagen hair. Current practice for many laboratories is that a single hair may not be subjected to DNA testing as there is little chance of success, hence this 100 % success rate from anagen hairs is a significant advancement. A full DNA profile was obtained from a 5 year-old single hair illustrating the success when using direct PCR rather than attempting an extraction prior to the amplification step. The process described deliberately uses current DNA profiling methods with no increase in cycle number, such that the methodology can be incorporated readily into operational practice. For the first time in the field of human identification, single hairs can be analyzed with confidence that a meaningful DNA profile will be generated and the data accepted by the criminal justice system.

  16. Stable transfection and identification of a hair follicle-specific expression vector of IGFBP-5 in goat fetal fibroblasts.

    PubMed

    Wang, X J; Su, H M; Liang, Y; Wang, Y F; Guo, X D; Wang, Z G; Liu, D J

    2014-03-17

    The insulin-like growth factor-binding protein-5 (IGFBP-5) is one of the 6 members of the IGFBP family and is involved in the regulation of cell growth, apoptosis, and other IGF-stimulated signaling pathways. To determine the significance of IGFBP-5 in the Inner Mongolia Cashmere goat (Capra hircus), a hair follicle-specific expression vector of IGFBP-5, pCDsRed2-K-IGFBP5 (6.7 kb), was constructed by cloning IGFBP-5 downstream of the keratin-association protein (KAP)6-1 promoter and inserting this fragment into pCDsRed2, which contains a red fluorescent protein (DsRed) expression unit. Inner Mongolia Cashmere goat fetal fibroblast (GFb) cells were transfected with the expression vector by using Lipofectamine(TM) 2000. Cell clones that stably expressed red fluorescence were obtained after selection with Geneticin (G418). The transgene in the cell clones was examined by polymerase chain reaction to verify that exogenous DNA (pKAP6-1 and IGFBP-5) had integrated stably into GFb cells. These data suggest that this method can be used for the construction of a hair follicle-specific expression vector for functional genetic analyses and for obtaining stable transfection donor cells for nuclear transfer.

  17. CD133 expression correlates with membrane beta-catenin and E-cadherin loss from human hair follicle placodes during morphogenesis.

    PubMed

    Gay, Denise L; Yang, Chao-Chun; Plikus, Maksim V; Ito, Mayumi; Rivera, Charlotte; Treffeisen, Elsa; Doherty, Laura; Spata, Michelle; Millar, Sarah E; Cotsarelis, George

    2015-01-01

    Genetic studies suggest that the major events of human hair follicle development are similar to those in mice, but detailed analyses of this process are lacking. In mice, hair follicle placode "budding" is initiated by invagination of Wnt-induced epithelium into the underlying mesenchyme. Modification of adherens junctions (AJs) is clearly required for budding. Snail-mediated downregulation of AJ component E-cadherin is important for placode budding in mice. Beta-catenin, another AJ component, has been more difficult to study owing to its essential functions in Wnt signaling, a prerequisite for hair follicle placode induction. Here, we show that a subset of human invaginating hair placode cells expresses the stem cell marker CD133 during early morphogenesis. CD133 associates with membrane beta-catenin in early placodes, and its continued expression correlates with loss of beta-catenin and E-cadherin from the cell membrane at a time when E-cadherin transcriptional repressors Snail and Slug are not implicated. Stabilization of CD133 via anti-CD133 antibody treatment of human fetal scalp explants depresses beta-catenin and E-cadherin membrane localization. We discuss this unique correlation and suggest a hypothetical model whereby CD133 promotes morphogenesis in early hair follicle placodes through the localized removal of membrane beta-catenin proteins and subsequent AJ dissolution.

  18. Localization of the rabies virus antigen in Merkel cells in the follicle-sinus complexes of muzzle skins of rabid dogs.

    PubMed

    Shimatsu, Taichi; Shinozaki, Harumi; Kimitsuki, Kazunori; Shiwa, Nozomi; Manalo, Daria L; Perez, Rodolfo C; Dilig, Joselito E; Yamada, Kentaro; Boonsriroj, Hassadin; Inoue, Satoshi; Park, Chun-Ho

    2016-11-01

    The direct fluorescent antibody test (dFAT) on fresh brain tissues is the gold standard for rabies virus antigen detection in dogs. However, this method is laborious and holds a high risk of virus exposure for the experimenter. Skin biopsies are useful for the diagnosis of humans and animals. In mammals, the tactile hair, known as the follicle-sinus complex (FSC), is a specialized touch organ that is abundant in the muzzle skin. Each tactile hair is equipped with more than 2,000 sensory nerve endings. Therefore, this organ is expected to serve as an alternative postmortem diagnostic material. However, the target cells and localization of rabies virus antigen in the FSCs remain to be defined. In the present study, muzzle skins were obtained from 60 rabid dogs diagnosed with rabies by dFAT at the Research Institute of Tropical Medicine in the Philippines. In all dogs, virus antigen was clearly detected in a part of the outer root sheath at the level of the ring sinus of the FSCs, and the majority of cells were positive for the Merkel cell (MC) markers cytokeratin 20 and CAM5.2. Our results suggest that MCs in the FSCs of the muzzle skin are a target for virus replication and could serve as a useful alternative specimen source for diagnosis of rabies.

  19. Concentration of heavy metals in hair and skin of silver and red foxes (Vulpes vulpes).

    PubMed

    Filistowicz, Andrzej; Dobrzański, Zbigniew; Przysiecki, Piotr; Nowicki, Sławomir; Filistowicz, Aneta

    2011-11-01

    The structure of hair and levels of main chemical elements (C, N, O, S, Cl, Ca, P, Al, Na) in the external layer of hair of silver and red foxes (Vulpes vulpes) in a non-industrialised, typically agricultural region of middle-west Poland was assessed using a scanning microscope. Additionally, analysis of the accumulation of certain heavy metals (Cr, Cu, Ni, Pb and Zn) in hair (washed) and skin (non-tanned) of those foxes was conducted. Heavy metal levels were determined using a spectrophotometric method (ICP-OES), and correlations between these levels in hair and skin were calculated. The microscopic external (morphological) and internal structures (histological) of the hair of farm and wild foxes were not differentiated; however, the hair of farm foxes (external layer) contained higher amounts of C, Na, Al and P. A significantly higher Pb content was noted in non-tanned skin of wild foxes in comparison to farm ones. In the case of farm foxes, a significantly higher Zn content in hair and Zn and Cu in skin was observed in comparison to wild ones. Positive significant correlations between Cr and Ni content (r = 0.622) and Zn and Cu (r = 0.721) in fox skin were noted. A similar relationship between Cr content in hair and Ni in skin (r = 0.643) and between Zn in hair and skin (r = 0.595) was also observed.

  20. Hair removal.

    PubMed

    Haedersdal, Merete; Haak, Christina S

    2011-01-01

    Hair removal with optical devices has become a popular mainstream treatment that today is considered the most efficient method for the reduction of unwanted hair. Photothermal destruction of hair follicles constitutes the fundamental concept of hair removal with red and near-infrared wavelengths suitable for targeting follicular and hair shaft melanin: normal mode ruby laser (694 nm), normal mode alexandrite laser (755 nm), pulsed diode lasers (800, 810 nm), long-pulse Nd:YAG laser (1,064 nm), and intense pulsed light (IPL) sources (590-1,200 nm). The ideal patient has thick dark terminal hair, white skin, and a normal hormonal status. Currently, no method of lifelong permanent hair eradication is available, and it is important that patients have realistic expectations. Substantial evidence has been found for short-term hair removal efficacy of up to 6 months after treatment with the available systems. Evidence has been found for long-term hair removal efficacy beyond 6 months after repetitive treatments with alexandrite, diode, and long-pulse Nd:YAG lasers, whereas the current long-term evidence is sparse for IPL devices. Treatment parameters must be adjusted to patient skin type and chromophore. Longer wavelengths and cooling are safer for patients with darker skin types. Hair removal with lasers and IPL sources are generally safe treatment procedures when performed by properly educated operators. However, safety issues must be addressed since burns and adverse events do occur. New treatment procedures are evolving. Consumer-based treatments with portable home devices are rapidly evolving, and presently include low-level diode lasers and IPL devices.

  1. Hypoxia Enhances Differentiation of Hair Follicle-Associated-Pluripotent (HAP) Stem Cells to Cardiac-Muscle Cells.

    PubMed

    Shirai, Kyoumi; Hamada, Yuko; Arakawa, Nobuko; Yamazaki, Aiko; Tohgi, Natsuko; Aki, Ryoichi; Mii, Sumiyuki; Hoffman, Robert M; Amoh, Yasuyuki

    2017-03-01

    We have previously demonstrated that the neural stem-cell marker nestin is expressed in hair-follicle stem cells located in the bulge area which are termed hair-follicle-associated pluripotent (HAP) stem cells. HAP stem cells from mouse and human could form spheres in culture, termed hair spheres, which are keratin 15-negative and nestin-positive and could differentiate to neurons, glia, keratinocytes, smooth muscle cells, and melanocytes in vitro. Subsequently, we demonstrated that nestin-expressing stem cells could effect nerve and spinal cord regeneration in mouse models. Recently, we demonstrated that HAP stem cells differentiated to beating cardiac muscle cells. We recently observed that isoproterenol directs HAP stem cells to differentiate to cardiac-muscle cells in large numbers in culture compared to HAP stem cells not supplemented with isoproterenol. The addition of activin A, bone morphogenetic protein 4, and basic fibroblast growth factor, along with isoproternal, induced the cardiac muscle cells to form tissue sheets of beating heart muscle cells. In the present study, we report that, under hypoxic conditions, HAP stem cells differentiated to troponin-positive cardiac-muscle cells at a higher rate that under normoxic conditions. Hypoxia did not influence the differentiation to other cell types. For future use of HAP stem cells for cardiac muscle regeneration, hypoxia should enhance the rate of differentiation thereby providing patients more opportunities to use their own HAP stem cells which are easily accessible, for this purpose. J. Cell. Biochem. 118: 554-558, 2017. © 2016 Wiley Periodicals, Inc.

  2. BMP Signaling and Its pSMAD1/5 Target Genes Differentially Regulate Hair Follicle Stem Cell Lineages

    PubMed Central

    Genander, Maria; Cook, Peter J.; Ramsköld, Daniel; Keyes, Brice E.; Mertz, Aaron F.; Sandberg, Rickard; Fuchs, Elaine

    2014-01-01

    Hair follicle stem cells (HFSCs) and their transit amplifying cell (TAC) progeny sense BMPs at defined stages of the hair cycle to control their proliferation and differentiation. Here, we exploit the distinct spatial and temporal localizations of these cells to selectively ablate BMP signaling in each compartment and examine its functional role. We find that BMP signaling is required for HFSC quiescence and to promote TAC differentiation along different lineages as the hair cycle progresses. We also combine in vivo genome-wide chromatin immunoprecipitation and deep-sequencing, transcriptional profiling, and loss-of-function genetics to define BMP-regulated genes. We show that some pSMAD1/5 targets, like Gata3, function specifically in TAC lineage-progression. Others, like Id1 and Id3, function in both HFSCs and TACs, but in distinct ways. Our study therefore illustrates the complex differential roles that a key signaling pathway can play in regulation of closely-related stem/progenitor cells within the context of their overall niche. PMID:25312496

  3. Feasibility of human hair follicle-derived mesenchymal stem cells/CultiSpher(®)-G constructs in regenerative medicine.

    PubMed

    Li, Pengdong; Liu, Feilin; Wu, Chunling; Jiang, Wenyue; Zhao, Guifang; Liu, Li; Bai, Tingting; Wang, Li; Jiang, Yixu; Guo, Lili; Qi, Xiaojuan; Kou, Junna; Fan, Ruirui; Hao, Deshun; Lan, Shaowei; Li, Yulin; Liu, Jin Yu

    2015-10-01

    The use of human mesenchymal stem cells (hMSCs) in cell therapies has increased the demand for strategies that allow efficient cell scale-up. Preliminary data on the three-dimensional (3D) spinner culture describing the potential use of microcarriers for hMSCs culture scale-up have been reported. We exploited a rich source of autologous stem cells (human hair follicle) and demonstrated the robust in vitro long-term expansion of human hair follicle-derived mesenchymal stem cells (hHF-MSCs) by using CultiSpher(®)-G microcarriers. We analyzed the feasibility of 3D culture by using hHF-MSCs/CultiSpher(®)-G microcarrier constructs for its potential applicability in regenerative medicine by comparatively analyzing the performance of hHF-MSCs adhered to the CultiSpher(®)-G microspheres in 3D spinner culture and those grown on the gelatin-coated plastic dishes (2D culture), using various assays. We showed that the hHF-MSCs seeded at various densities quickly adhered to and proliferated well on the microspheres, thus generating at least hundreds of millions of hHF-MSCs on 1 g of CultiSpher(®)-G within 12 days. This resulted in a cumulative cell expansion of greater than 26-fold. Notably, the maximum and average proliferation rates in 3D culture were significantly greater than that of the 2D culture. However, the hHF-MSCs from both the cultures retained surface marker and nestin expression, proliferation capacity and differentiation potentials toward adipocytes, osteoblasts and smooth muscle cells and showed no significant differences as evidenced by Edu incorporation, cell cycle, colony formation, apoptosis, biochemical quantification and qPCR assays.

  4. In vivo formation steps of the hard alpha-keratin intermediate filament along a hair follicle: evidence for structural polymorphism.

    PubMed

    Rafik, Mériem Er; Briki, Fatma; Burghammer, Manfred; Doucet, Jean

    2006-04-01

    Several aspects of the intermediate filaments' molecular architecture remain mysterious despite decades of study. The growth process and the final architecture may depend on the physical, chemical, and biochemical environment. Aiming at clarifying this issue, we have revisited the structure of the human hair follicle by means of X-ray microdiffraction. We conclude that the histology-based growth zones along the follicle are correlated to the fine architecture of the filaments deduced from X-ray microdiffraction. Our analysis reveals the existence of two major polymorph intermediate filament architectures. Just above the bulb, the filaments are characterized by a diameter of 100 Angstroms and a low-density core. The following zone upwards is characterized by the lateral aggregation of the filaments into a compact network of filaments, by a contraction of their diameter (to 75 Angstroms) and by the setting up of a long-range longitudinal ordering. In the upper zone, the small structural change associated with the tissue hardening likely concerns the terminal domains. The architecture of the intermediate filament in the upper zones could be specific to hard alpha-keratin whilst the other architecture found in the lower zone could be representative for intermediate filaments in a different environment.

  5. Profiling mRNA of the graying human hair follicle constitutes a promising state-of-the-art tool to assess its aging: an exemplary report.

    PubMed

    Peters, Eva M J; Liezmann, Christiane; Spatz, Katharina; Ungethüm, Ute; Kuban, Ralf-Jürgen; Daniltchenko, Maria; Kruse, Johannes; Imfeld, Dominik; Klapp, Burghard F; Campiche, Remo

    2013-05-01

    Determining hitherto uninvestigated and safe targets to halt the aging process is important in our aging society. Graying is a hallmark of the aging process and may be used to identify aging tissue for comparative analysis. Here we analyzed differential gene expressions between pigmented, gray, and white human scalp skin hair follicles (HFs) from identical donors. Forming intersections between five donors identified 194/192 downregulated and 186/177 upregulated genes in gray/white HFs. These included melanogenesis (tyrosinase; tyrosinase-related protein 1)- and melanosome structure (Melan-A; Pmel17)-associated genes and regulation of melanocyte relevant tyrosine kinases. Alongside these expected changes, regulated genes included nonmelanocyte-related genes associated with aging as well as nonaging-related genes associated with melanocytes. Intriguingly, among them, genes associated with energy metabolism (i.e., glutaminase) and axon guidance (plexin C1) were altered. These results were reflected by pathway analysis and exemplarily confirmed by PCR and immunohistochemical studies. Supplementing cultured HFs with glutamine or plexin C1 revealed biological relevance and pharmacointerventional potential of these microarray results in altering the HF aging process. Together, we present intriguing data obtained from intra-individual sample comparison that suggest the graying HF to be a valid aging model and a promising target for testing therapeutic interventions.

  6. 15-deoxy prostaglandin J2, the nonenzymatic metabolite of prostaglandin D2, induces apoptosis in keratinocytes of human hair follicles: a possible explanation for prostaglandin D2-mediated inhibition of hair growth.

    PubMed

    Joo, Hyun Woo; Kang, Yoo Ri; Kwack, Mi Hee; Sung, Young Kwan

    2016-07-01

    Recent studies have shown that prostaglandin D2 (PGD2) and its nonenzymatic metabolite, 15-deoxy-Δ(12,14)-prostaglandin J2 (15-dPGJ2), inhibit in vitro growth of explanted human hair follicles and inhibit hair growth in mice through the GPR44 (DP2). However, the underlying mechanism is still unclear. In this study, we first investigated the expression of DP2 in human hair follicles and in cultured follicular cells. We found that DP2 is strongly expressed in the outer root sheath (ORS) cells and weakly expressed in the dermal papilla (DP) cells. We observed slight growth stimulation when ORS and DP cells were treated with PGD2. We also observed slight growth stimulation when DP and ORS cells were treated with low concentrations (0.5 and 1 μM) of 15-dPGJ2. However, 5 μM 15-dPGJ2 inhibited the viability and caused apoptosis of both cell types. Exposure of cultured human hair follicles to 15-dPGJ2 resulted in significant apoptosis in follicular keratinocytes. Altogether, our data provide an evidence that 15-dPGJ2 promotes apoptosis in follicular keratinocytes and provide rationale for developing remedies for the prevention and treatment of hair loss based on DP2 antagonism.

  7. Laser assisted hair-removal.

    PubMed

    Choudhary, S; Elsaie, M L; Nouri, K

    2009-10-01

    A number of lasers and light devices are now available for the treatment of unwanted hair. The goal of laser hair removal is to damage stem cells in the bulge of the hair follicle by targeting melanin, the endogenous chromophore for laser and light devices utilized to remove hair. The competing chromophores in the skin and hair, oxyhemoglobin and water, have a decreased absorption between 690 nm and 1000 nm, thus making this an ideal range for laser and light sources. Laser hair removal is achieved through follicular unit destruction based on selective photothermolysis. The principle of selective photothermolysis predicts that the thermal injury will be restricted to a given target if there is sufficient selective absorption of light and the pulse duration is shorter than the thermal relaxation time of the target. This review will focus on the mechanisms of laser assisted hair removal and provide an update on the newer technologies emerging in the field of lasers assisted hair removal.

  8. Herbal Extracts Induce Dermal Papilla Cell Proliferation of Human Hair Follicles

    PubMed Central

    Rastegar, Hosein; Aghaei, Mahmoud; Barikbin, Behrooz; Ehsani, Amirohushang

    2015-01-01

    Background The number of people suffering from balding or hair thinning is increasing, despite the advances in various medical therapies. Therefore, it is highly important to develop new therapies to inhibit balding and increase hair proliferation. Objective We investigated the effects of herbal extracts commonly used for improving balding in traditional medicine to identify potential agents for hair proliferation. Methods The expression levels of 5α-reductase isoforms (type I and II) were analyzed using quantitative real-time reverse transcription polymerase chain reaction in the human follicular dermal papilla cells (DPCs). The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenylteterazolium bromide and bromodeoxyuridine tests were used to evaluate the cell proliferation effect of herbal extracts in DPCs. The expression levels of extracellular signal-regulated kinase (ERK), Akt, cyclin D1, cyclin-dependent kinase 4 (Cdk4), B-cell lymphoma (Bcl-2) and Bcl-2-associated X protein (Bax) were measured using western blot analysis. Results The 5α-reductase isoform mRNAs and proteins were detected in the cultured DPCs, and the expression level of 5α-R2 in DPCs in the presence of the herbal extracts was gradually decreased. Herbal extracts were found to significantly increase the proliferation of human DPCs at concentrations ranging from 1.5% to 4.5%. These results show that the herbal extracts tested affected the protein expressions of ERK, Akt, cyclin D1, Cdk4, Bcl-2, and Bax in DPCs. Conclusion These results suggest that herbal extracts exert positive effects on hair proliferation via ERK, Akt, cyclin D1, and Cdk4 signaling in DPCs; they also suggest that herbal extracts could be a great alternative therapy for increasing hair proliferation. PMID:26719634

  9. Aging changes in hair and nails

    MedlinePlus

    ... of aging. Hair color is due to a pigment called melanin , which hair follicles produce. Follicles are ... slows. Hair strands become smaller and have less pigment. So the thick, coarse hair of a young ...

  10. A Novel Mechanism for the Pathogenesis of Nonmelanoma Skin Cancer Resulting from Early Exposure to Ultraviolet Light

    DTIC Science & Technology

    2013-09-01

    is expressed on approximately 27% of CD49f+/CD34+ hair follicle stem cells and suggesting that these cells may have the capacity to follow an...the stem cells of the hair follicles because they not only serve as a reservoir of epidermal cells, they also possess remarkable regenerative potential...response to sunburn. We address the following question: Do hair follicle stem cells migrate from the skin following sunburn as a consequence of ultraviolet

  11. EZH1 and EZH2 cogovern histone H3K27 trimethylation and are essential for hair follicle homeostasis and wound repair

    PubMed Central

    Ezhkova, Elena; Lien, Wen-Hui; Stokes, Nicole; Pasolli, H. Amalia; Silva, Jose M.; Fuchs, Elaine

    2011-01-01

    Polycomb protein group (PcG)-dependent trimethylation on H3K27 (H3K27me3) regulates identity of embryonic stem cells (ESCs). How H3K27me3 governs adult SCs and tissue development is unclear. Here, we conditionally target H3K27 methyltransferases Ezh2 and Ezh1 to address their roles in mouse skin homeostasis. Postnatal phenotypes appear only in doubly targeted skin, where H3K27me3 is abolished, revealing functional redundancy in EZH1/2 proteins. Surprisingly, while Ezh1/2-null hair follicles (HFs) arrest morphogenesis and degenerate due to defective proliferation and increased apoptosis, epidermis hyperproliferates and survives engraftment. mRNA microarray studies reveal that, despite these striking phenotypic differences, similar genes are up-regulated in HF and epidermal Ezh1/2-null progenitors. Featured prominently are (1) PcG-controlled nonskin lineage genes, whose expression is still significantly lower than in native tissues, and (2) the PcG-regulated Ink4a/Inkb/Arf locus. Interestingly, when EZH1/2 are absent, even though Ink4a/Arf/Ink4b genes are fully activated in HF cells, they are only partially so in epidermal progenitors. Importantly, transduction of Ink4b/Ink4a/Arf shRNAs restores proliferation/survival of Ezh1/2-null HF progenitors in vitro, pointing toward the relevance of this locus to the observed HF phenotypes. Our findings reveal new insights into Polycomb-dependent tissue control, and provide a new twist to how different progenitors within one tissue respond to loss of H3K27me3. PMID:21317239

  12. Ingrown Hair

    MedlinePlus

    ... like lesions (pustules) Skin darkening (hyperpigmentation) Pain Itching Embedded hairs When to see a doctor An occasional ... inserting it under hair loops, to gently lift embedded hair tips. To help prevent ingrown hairs, avoid ...

  13. Androgens and hair growth.

    PubMed

    Randall, Valerie Anne

    2008-01-01

    Hair's importance in human communication means that abnormalities like excess hair in hirsutism or hair loss in alopecia cause psychological distress. Androgens are the main regulator of human hair follicles, changing small vellus follicles producing tiny, virtually invisible hairs into larger intermediate and terminal follicles making bigger, pigmented hairs. The response to androgens varies with the body site as it is specific to the hair follicle itself. Normally around puberty, androgens stimulate axillary and pubic hair in both sexes, plus the beard, etc. in men, while later they may also inhibit scalp hair growth causing androgenetic alopecia. Androgens act within the follicle to alter the mesenchyme-epithelial cell interactions, changing the length of time the hair is growing, the dermal papilla size and dermal papilla cell, keratinocyte and melanocyte activity. Greater understanding of the mechanisms of androgen action in follicles should improve therapies for poorly controlled hair disorders like hirsutism and alopecia.

  14. Bad Hair Day: Testosterone and Wnts

    PubMed Central

    Nelson, Amanda M.; Garza, Luis A.

    2016-01-01

    Androgens have an important role in normal skin physiology, as well as in the pathogenesis of many skin conditions, such as acne vulgaris, hirsutism, and androgenic alopecia. Kretzchumar et al. (2015) investigate the relationship between androgen receptor (AR) signaling and β-catenin/Wnt signaling pathways in murine hair follicles. PMID:26548488

  15. Bad Hair Day: Testosterone and Wnts.

    PubMed

    Nelson, Amanda M; Garza, Luis A

    2015-11-01

    Androgens have an important role in normal skin physiology, as well as in the pathogenesis of many skin conditions, such as acne vulgaris, hirsutism, and androgenic alopecia. Kretzchumar et al. (2015) investigate the relationship between androgen receptor (AR) signaling and β-catenin/Wnt signaling pathways in murine hair follicles.

  16. An Integrated Analysis of MicroRNA and mRNA Expression Profiles to Identify RNA Expression Signatures in Lambskin Hair Follicles in Hu Sheep

    PubMed Central

    Lv, Xiaoyang; Sun, Wei; Yin, Jinfeng; Ni, Rong; Su, Rui; Wang, Qingzeng; Gao, Wen; Bao, Jianjun; Yu, Jiarui; Wang, Lihong; Chen, Ling

    2016-01-01

    Wave patterns in lambskin hair follicles are an important factor determining the quality of sheep’s wool. Hair follicles in lambskin from Hu sheep, a breed unique to China, have 3 types of waves, designated as large, medium, and small. The quality of wool from small wave follicles is excellent, while the quality of large waves is considered poor. Because no molecular and biological studies on hair follicles of these sheep have been conducted to date, the molecular mechanisms underlying the formation of different wave patterns is currently unknown. The aim of this article was to screen the candidate microRNAs (miRNA) and genes for the development of hair follicles in Hu sheep. Two-day-old Hu lambs were selected from full-sib individuals that showed large, medium, and small waves. Integrated analysis of microRNA and mRNA expression profiles employed high-throughout sequencing technology. Approximately 13, 24, and 18 differentially expressed miRNAs were found between small and large waves, small and medium waves, and medium and large waves, respectively. A total of 54, 190, and 81 differentially expressed genes were found between small and large waves, small and medium waves, and medium and large waves, respectively, by RNA sequencing (RNA-seq) analysis. Differentially expressed genes were classified using gene ontology and pathway analyses. They were found to be mainly involved in cell differentiation, proliferation, apoptosis, growth, immune response, and ion transport, and were associated with MAPK and the Notch signaling pathway. Reverse transcription-polymerase chain reaction (RT-PCR) analyses of differentially-expressed miRNA and genes were consistent with sequencing results. Integrated analysis of miRNA and mRNA expression indicated that, compared to small waves, large waves included 4 downregulated miRNAs that had regulatory effects on 8 upregulated genes and 3 upregulated miRNAs, which in turn influenced 13 downregulated genes. Compared to small waves

  17. Nestin-expressing stem cells from the hair follicle can differentiate into motor neurons and reduce muscle atrophy after transplantation to injured nerves.

    PubMed

    Liu, Fang; Zhang, Chuansen; Hoffman, Robert M

    2014-02-01

    We have previously shown that nestin-expressing hair follicle stem cells from the mouse and human are multipotent and can differentiate into many cell types, including neurons and glial cells. The nestin-expressing hair follicle stem cells can effect nerve and spinal cord repair upon transplantation in mouse models. In the present study, nestin-expressing hair follicle stem cells expressing red fluorescent protein (RFP) were induced by retinoic acid and fetal bovine serum to differentiate and then transplanted together with Matrigel into the transected distal sciatic or tibial nerve stump of transgenic nude mice ubiquitously expressing green fluorescent protein (GFP). Control mice were transplanted with Matrigel only. The transplanted cells appeared neuron like, with large round nuclei and long extensions. Immunofluorescence staining showed that some of the transplanted cells in the distal nerve stump expressed the neuron marker Tuj1 as well as motor neuron markers Isl 1/2 and EN1. These transplanted cells contacted each other as well as host nerve fibers. Two weeks post-transplantation, nerve fibers in the distal sciatic nerve stump of the transplanted mice had greater expression of motor neuron markers and neurotrophic factor-3 than those in the Matrigel-only transplanted mice. Muscle fiber areas in the nestin-expressing stem cell plus Matrigel-transplanted animals were much bigger than that in the Matrigel-only transplanted animals after 4 weeks. The present results suggest that transplanted nestin-expressing hair follicle stem cells can differentiate into motor neurons and reduce muscle atrophy after sciatic nerve transection. This study demonstrates a new and accessible neuron source to reduce muscle atrophy after nerve injury.

  18. A robust hair segmentation and removal approach for clinical images of skin lesions.

    PubMed

    Huang, Adam; Kwan, Shun-Yuen; Chang, Wen-Yu; Liu, Min-Yin; Chi, Min-Hsiu; Chen, Gwo-Shing

    2013-01-01

    Artifacts such as hair are major obstacles to automatic segmentation of pigmented skin lesion images for computer-aided diagnosis systems. It is even more challenging to process clinical images taken by a regular digital camera, where the shadows of the skin texture may mimic hair-like curvilinear structures. In this study, we examined the popular DullRazor software with a dataset of 20 clinical images. The software, specifically designed for dermoscopic images, was unable to remove fine hairs or hairs in the shade. Alternatively, we proposed using conventional matched filters to enhance curvilinear structures. The more complicate hair intersection patterns, which were known to generate low matched filtering responses, were recovered by using region growing algorithms from nearby detected hair segments with linear discriminant analysis (LDA) based on a color similarity criterion. The preliminary results indicated the proposed method was able to remove more fine hairs and hairs in the shade, and lower false hair detection rate by 58% (from 0.438 to 0.183) as compared to the DullRazor's approach.

  19. FOXC1 maintains the hair follicle stem cell niche and governs stem cell quiescence to preserve long-term tissue-regenerating potential.

    PubMed

    Lay, Kenneth; Kume, Tsutomu; Fuchs, Elaine

    2016-03-15

    Adult tissue stem cells (SCs) reside in niches, which orchestrate SC behavior. SCs are typically used sparingly and exist in quiescence unless activated for tissue growth. Whether parsimonious SC use is essential to conserve long-term tissue-regenerating potential during normal homeostasis remains poorly understood. Here, we examine this issue by conditionally ablating a key transcription factor Forkhead box C1 (FOXC1) expressed in hair follicle SCs (HFSCs). FOXC1-deficient HFSCs spend less time in quiescence, leading to markedly shortened resting periods between hair cycles. The enhanced hair cycling accelerates HFSC expenditure, and impacts hair regeneration in aging mice. Interestingly, although FOXC1-deficient HFs can still form a new bulge that houses HFSCs for the next hair cycle, the older bulge is left unanchored. As the new hair emerges, the entire old bulge, including its reserve HFSCs and SC-inhibitory inner cell layer, is lost. We trace this mechanism first, to a marked increase in cell cycle-associated transcripts upon Foxc1 ablation, and second, to a downstream reduction in E-cadherin-mediated inter-SC adhesion. Finally, we show that when the old bulge is lost with each hair cycle, overall levels of SC-inhibitory factors are reduced, further lowering the threshold for HFSC activity. Taken together, our findings suggest that HFSCs have restricted potential in vivo, which they conserve by coupling quiescence to adhesion-mediated niche maintenance, thereby achieving long-term tissue homeostasis.

  20. FOXC1 maintains the hair follicle stem cell niche and governs stem cell quiescence to preserve long-term tissue-regenerating potential

    PubMed Central

    Lay, Kenneth; Kume, Tsutomu; Fuchs, Elaine

    2016-01-01

    Adult tissue stem cells (SCs) reside in niches, which orchestrate SC behavior. SCs are typically used sparingly and exist in quiescence unless activated for tissue growth. Whether parsimonious SC use is essential to conserve long-term tissue-regenerating potential during normal homeostasis remains poorly understood. Here, we examine this issue by conditionally ablating a key transcription factor Forkhead box C1 (FOXC1) expressed in hair follicle SCs (HFSCs). FOXC1-deficient HFSCs spend less time in quiescence, leading to markedly shortened resting periods between hair cycles. The enhanced hair cycling accelerates HFSC expenditure, and impacts hair regeneration in aging mice. Interestingly, although FOXC1-deficient HFs can still form a new bulge that houses HFSCs for the next hair cycle, the older bulge is left unanchored. As the new hair emerges, the entire old bulge, including its reserve HFSCs and SC-inhibitory inner cell layer, is lost. We trace this mechanism first, to a marked increase in cell cycle-associated transcripts upon Foxc1 ablation, and second, to a downstream reduction in E-cadherin–mediated inter-SC adhesion. Finally, we show that when the old bulge is lost with each hair cycle, overall levels of SC-inhibitory factors are reduced, further lowering the threshold for HFSC activity. Taken together, our findings suggest that HFSCs have restricted potential in vivo, which they conserve by coupling quiescence to adhesion-mediated niche maintenance, thereby achieving long-term tissue homeostasis. PMID:26912458

  1. Glutamatergic modulation of synaptic-like vesicle recycling in mechanosensory lanceolate nerve terminals of mammalian hair follicles.

    PubMed

    Banks, Robert W; Cahusac, Peter M B; Graca, Anna; Kain, Nakul; Shenton, Fiona; Singh, Paramjeet; Njå, Arild; Simon, Anna; Watson, Sonia; Slater, Clarke R; Bewick, Guy S

    2013-05-15

    Our aim in the present study was to determine whether a glutamatergic modulatory system involving synaptic-like vesicles (SLVs) is present in the lanceolate ending of the mouse and rat hair follicle and, if so, to assess its similarity to that of the rat muscle spindle annulospiral ending we have described previously. Both types of endings are formed by the peripheral sensory terminals of primary mechanosensory dorsal root ganglion cells, so the presence of such a system in the lanceolate ending would provide support for our hypothesis that it is a general property of fundamental importance to the regulation of the responsiveness of the broad class of primary mechanosensory endings. We show not only that an SLV-based system is present in lanceolate endings, but also that there are clear parallels between its operation in the two types of mechanosensory endings. In particular, we demonstrate that, as in the muscle spindle: (i) FM1-43 labels the sensory terminals of the lanceolate ending, rather than the closely associated accessory (glial) cells; (ii) the dye enters and leaves the terminals primarily by SLV recycling; (iii) the dye does not block the electrical response to mechanical stimulation, in contrast to its effect on the hair cell and dorsal root ganglion cells in culture; (iv) SLV recycling is Ca(2+) sensitive; and (v) the sensory terminals are enriched in glutamate. Thus, in the lanceolate sensory ending SLV recycling is itself regulated, at least in part, by glutamate acting through a phospholipase D-coupled metabotropic glutamate receptor.

  2. A Comparative Study of Melanin Content and Skin Morphology for Three Commonly Used Laboratory Swine (Sus scrofa domestica)

    DTIC Science & Technology

    2012-09-01

    Extensive fat deposits below subcutis Vasculization of hair follicles Seasonally regulated hair shedding Structure of the collagenous tissue...comparison (p-values) of skin thickness between breeds. Segments in gray indicate statistically different variances (F- test ) or means (t- test ...2004, Pg. 475). Note that keratinocytes produce keratin, the primary constituent for hair . Melanosomes enter the hair when it is being formed

  3. Skin surface lipids and skin and hair coat condition in dogs fed increased total fat diets containing polyunsaturated fatty acids.

    PubMed

    Kirby, N A; Hester, S L; Rees, C A; Kennis, R A; Zoran, D L; Bauer, J E

    2009-08-01

    It is generally believed that diets containing increased amounts of polyunsaturated fatty acids (PUFA) result in improved canine skin and hair coat (SHC). However, the extent to which dietary fat amount and type play a role remains to be systematically investigated. The objective of this study was to investigate the role of both increased dietary fat amount and type on SHC assessments of dogs. Improvements of SHC conditions were investigated after feeding three diets containing increased total dietary fat (i.e. 13% total fat) for 12 weeks in relation to a lower fat acclimation diet (i.e. 9% total fat). The higher fat diets varied in polyunsaturated and saturated fat types and amounts but total fat was kept constant. Skin and hair coat assessments were performed at selected intervals by a trained group of veterinarians and graduate students. In addition, hair lipids were fractionated by thin layer chromatography after extraction of plucked hair samples. Significant improvements were found in hair coat glossiness and softness in all dogs fed the higher fat diets in relation to the acclimation diet. Improvements as a result of fat type were also seen but only at 12 weeks. A parallel finding was a marked increase in hair cholesteryl ester content determined at the end of the study at which time SHC scores were significantly improved. Skin and hair coat condition improvements may thus be related to increased cholesteryl ester deposited on the hair shaft surface when high fat diets are fed. Whereas this finding is preliminary, hair lipid analysis may be a useful, non-invasive technique with which to help assess dietary effects on canine SHC.

  4. Human hair follicle and interfollicular keratinocyte reactivity to mouse HPV16-transformed cells: an in vitro study.

    PubMed

    Smetana, Karel; Dvoránková, Barbora; Lacina, Lukás; Cada, Zdenek; Vonka, Vladimír

    2008-07-01

    The role of stem cells in cancer formation and spreading has been established. As with normal tissue, the cancer stem cells need a special microenvironment to support their growth. This microenvironment may be represented by the tumor stroma. One of the possible ways of tumor stromal formation is the epithelial-mesenchymal transition of tumor epithelium. Following this mechanism, stromal cells must share the basic genetic alterations with the tumor cells. In an attempt to create a system capable of testing some aspects of the mesenchymal cell-keratinocyte interactions, we studied the effects of the fibroblastoid mouse TC-1 cells that were prepared by the introduction of human papillomavirus type 16 (HPV16) genes E6 and E7 to lung epithelial cells on the phenotype of normal human interfollicular and hair follicle keratinocytes. From this point of view, they may resemble stromal cells formed by the epithelial-mesenchymal transition of cells from HPV-induced squamous cell carcinoma. In contrast to 3T3 murine embryonic fibroblasts which were used as control cells, TC-1 cells influenced not only the size of the keratinocytes and the shape of their colonies, but also induced the expression of keratins 8 and 19 and vimentin. In conclusion, TC-1 cells exhibited a marked biological activity by influencing the behavior of the normal human follicular and intefollicular keratinocytes. This observation is compatible with the hypothesis that stromal cells play an important role in tumor progression and spreading.

  5. miR-128 regulates differentiation of hair follicle mesenchymal stem cells into smooth muscle cells by targeting SMAD2.

    PubMed

    Wang, Zhihao; Pang, Li; Zhao, Huiying; Song, Lei; Wang, Yuehui; Sun, Qi; Guo, Chunjie; Wang, Bin; Qin, Xiujiao; Pan, Aiqun

    2016-05-01

    Human hair follicle mesenchymal stem cells (hHFMSCs) are an important source of cardiovascular tissue engineering for their differentiation potential into smooth muscle cells (SMCs), yet the molecular pathways underlying such fate determination is unclear. MicroRNAs (miRNAs) are non-coding RNAs that play critical roles in cell differentiation. In present study, we found that miR-128 was remarkably decreased during the differentiation of hHFMSCs into SMCs induced by transforming growth factor-β1 (TGF-β1). Moreover, overexpression of miR-128 led to decreased expression of SMC cellular marker proteins, such as smooth muscle actin (SMA) and calponin, in TGF-β1-induced SMC differentiation. Further, we identified that miR-128 targeted the 3'-UTR of SMAD2 transcript for translational inhibition of SMAD2 protein, and knockdown of SMAD2 abrogated the promotional effect of antagomir-128 (miR-128 neutralizer) on SMC differentiation. These results suggest that miR-128 regulates the differentiation of hHFMSCs into SMCs via targeting SMAD2, a main transcription regulator in TGF-β signaling pathway involving SMC differentiation. The miR-128/SMAD2 axis could therefore be considered as a candidate target in tissue engineering and regenerative medicine for SMCs.

  6. Visualization of hair follicles using high-speed optical coherence tomography based on a Fourier domain mode locking laser

    NASA Astrophysics Data System (ADS)

    Tsai, M.-T.; Chang, F.-Y.

    2012-04-01

    In this study, a swept-source optical coherence tomography (SS-OCT) system with a Fourier domain mode locking (FDML) laser is proposed for a dermatology study. The homemade FDML laser is one kind of frequency-sweeping light source, which can provide output power of >20 mW and an output spectrum of 65 nm in bandwidth centered at 1300 nm, enabling imaging with an axial resolution of 12 μm in the OCT system. To eliminate the forward scans from the laser output and insert the delayed backward scans, a Mach-Zehnder configuration is implemented. Compared with conventional frequency-sweeping light sources, the FDML laser can achieve much higher scan rates, as high as ˜240 kHz, which can provide a three-dimensional imaging rate of 4 volumes/s. Furthermore, the proposed high-speed SS-OCT system can provide three-dimensional (3D) images with reduced motion artifacts. Finally, a high-speed SS-OCT system is used to visualize hair follicles, demonstrating the potential of this technology as a tool for noninvasive diagnosis of alopecia.

  7. A genome-wide association study identifies novel alleles associated with hair color and skin pigmentation.

    PubMed

    Han, Jiali; Kraft, Peter; Nan, Hongmei; Guo, Qun; Chen, Constance; Qureshi, Abrar; Hankinson, Susan E; Hu, Frank B; Duffy, David L; Zhao, Zhen Zhen; Martin, Nicholas G; Montgomery, Grant W; Hayward, Nicholas K; Thomas, Gilles; Hoover, Robert N; Chanock, Stephen; Hunter, David J

    2008-05-16

    We conducted a multi-stage genome-wide association study of natural hair color in more than 10,000 men and women of European ancestry from the United States and Australia. An initial analysis of 528,173 single nucleotide polymorphisms (SNPs) genotyped on 2,287 women identified IRF4 and SLC24A4 as loci highly associated with hair color, along with three other regions encompassing known pigmentation genes. We confirmed these associations in 7,028 individuals from three additional studies. Across these four studies, SLC24A4 rs12896399 and IRF4 rs12203592 showed strong associations with hair color, with p = 6.0x10(-62) and p = 7.46x10(-127), respectively. The IRF4 SNP was also associated with skin color (p = 6.2x10(-14)), eye color (p = 6.1x10(-13)), and skin tanning response to sunlight (p = 3.9x10(-89)). A multivariable analysis pooling data from the initial GWAS and an additional 1,440 individuals suggested that the association between rs12203592 and hair color was independent of rs1540771, a SNP between the IRF4 and EXOC2 genes previously found to be associated with hair color. After adjustment for rs12203592, the association between rs1540771 and hair color was not significant (p = 0.52). One variant in the MATP gene was associated with hair color. A variant in the HERC2 gene upstream of the OCA2 gene showed the strongest and independent association with hair color compared with other SNPs in this region, including three previously reported SNPs. The signals detected in a region around the MC1R gene were explained by MC1R red hair color alleles. Our results suggest that the IRF4 and SLC24A4 loci are associated with human hair color and skin pigmentation.

  8. Estrogenic and anti-estrogenic activity of off-the-shelf hair and skin care products

    PubMed Central

    Myers, Sharon L.; Yang, Chun Z.; Bittner, George D.; Witt, Kristine L.; Tice, Raymond R.; Baird, Donna D.

    2014-01-01

    Use of personal care products is widespread in the United States but tends to be greater among African Americans than whites. Of special concern is the possible hazard of absorption of chemicals with estrogenic activity (EA) or anti-EA (AEA) in these products. Such exposure may have adverse health effects, especially when it occurs during developmental windows (e.g., prepubertally) when estrogen levels are low. We assessed the ethanol extracts of eight commonly used hair and skin products popular among African Americans for EA and AEA using a cell proliferation assay with the estrogen sensitive MCF-7:WS8 cell line derived from a human breast cancer. Four of the eight personal care products tested (Oil Hair Lotion, Extra-dry Skin Lotion, Intensive Skin Lotion, Petroleum Jelly) demonstrated detectable EA, whereas three (Placenta Hair Conditioner, Tea-Tree Hair Conditioner, Cocoa Butter Skin Cream) exhibited AEA. Our data indicate that hair and skin care products can have EA or AEA, and suggest that laboratory studies are warranted to investigate the in vivo activity of such products under chronic exposure conditions as well as epidemiologic studies to investigate potential adverse health effects that might be associated with use of such products. PMID:24849798

  9. Nuclear aberrations in hair follicle cells of patients receiving cyclophosphamide. A possible in vivo assay for human exposure to genotoxic agents.

    PubMed

    Goldberg, M T; Tackaberry, L E; Hardy, M H; Noseworthy, J H

    1990-01-01

    The toxic effect of cyclophosphamide on the proliferative cell population of hair follicles plucked from the human scalp was examined by the in vivo nuclear aberration assay. Patients participating in an independent clinical trial received oral low dose cyclophosphamide, intravenous high dose cyclophosphamide or oral placebo treatment. The percent of cells with nuclear aberrations (indicating apoptosis, a special form of cell death) and the percent of mitotic cells, in the hair matrix, were calculated for each patient before treatment and at several time points following cyclophosphamide or placebo treatment. The mean percentages of nuclear aberrations in both the treated Low dose and High dose cyclophosphamide patients were significantly higher than those for the pre-treatment and Placebo patients. The nuclear aberrations in hair follicle cells increased from pre-treatment (and Placebo) to treated Low dose and finally to treated High dose patients. The average percentage for pre-treatment samples from all patients was 0.06 +/- 0.03 SE. For 1 week and 1 month samples from Low dose patients it was 0.35 +/- 0.08 SE, and for combined 2,3 and 4 day samples from High dose patients it was 1.08 +/- 0.12 SE. Cyclophosphamide also had a significant effect on mitosis. A decrease in mitotic activity was observed at 1 month following the initial low dose cyclophosphamide treatment and at 24 +/- 2 h following each of the first two high dose cyclophosphamide treatments. The observed increase in nuclear aberrations following low dose as well as high dose cyclophosphamide suggests that it is feasible to use the nuclear aberration assay for in vivo human genotoxicity testing, using proliferating hair follicle cells.

  10. Skin and hair on-a-chip: in vitro skin models versus ex vivo tissue maintenance with dynamic perfusion.

    PubMed

    Ataç, Beren; Wagner, Ilka; Horland, Reyk; Lauster, Roland; Marx, Uwe; Tonevitsky, Alexander G; Azar, Reza P; Lindner, Gerd

    2013-09-21

    Substantial progress has been achieved over the last few decades in the development of skin equivalents to model the skin as an organ. However, their static culture still limits the emulation of essential physiological properties crucial for toxicity testing and compound screening. Here, we describe a dynamically perfused chip-based bioreactor platform capable of applying variable mechanical shear stress and extending culture periods. This leads to improvements of culture conditions for integrated in vitro skin models, ex vivo skin organ cultures and biopsies of single hair follicular units.

  11. Stimulatory effect of Brazilian propolis on hair growth through proliferation of keratinocytes in mice.

    PubMed

    Miyata, Shota; Oda, Yozo; Matsuo, Chika; Kumura, Haruto; Kobayashi, Ken

    2014-12-10

    Propolis is a natural honeybee hive product with the potential for use in the treatment of dermatological conditions, such as cutaneous abrasions, burns, and acne. In this study, we investigated whether propolis stimulates hair growth in mice. Ethanol-extracted propolis, which contains various physiologically active substances such as caffeic acid and kaempferol, stimulated anagen induction in shaved back skin. Anagen induction occurred without any detectable abnormalities in the shape of the hair follicles (HFs), hair stem cells in the bulge, proliferating hair matrix keratinocytes in the hair bulb, or localization of versican in the dermal papilla. Propolis treatment also stimulated migration of hair matrix keratinocytes into the hair shaft in HFs during late anagen in the depilated back skin. Organotypic culture of skin containing anagen stage HFs revealed significant stimulation of hair matrix keratinocyte proliferation by propolis. Furthermore, propolis facilitated the proliferation of epidermal keratinocytes. These results indicate that propolis stimulates hair growth by inducing hair keratinocyte proliferation.

  12. Tooth, skin, hair and eye colour interrelationships in Greek young adults.

    PubMed

    Lagouvardos, Panagiotis E; Tsamali, Ioana; Papadopoulou, Christine; Polyzois, Gregory

    2013-01-01

    The purpose of this study was to investigate the possible interrelationships of teeth, skin, eye and hair colour. A portable colorimeter (Shade Eye NCC/Shofu) was used to record the colour in the CIELAB system of the upper right incisors in 150 dental school students, along with their skin colour at three different areas. Natural hair and eye colour was classified into several categories by a trained examiner (ICC 0.93-0.99). One-way ANOVA and correlation tests were used to statistically analyse the data. Skin was found to have significantly higher L*, b* but lower a* values than teeth (p < 0.05). A significant correlation (p < 0.05) of teeth to skin L* and a*colour coordinate was found, but not to b* coordinate (p > 0.05). Hair tones were not correlated to teeth L* or b*, but only to a*coordinate. Teeth and eye colour coordinates were not correlated (p > 0.05). Eye and hair tones were found to have the highest significant correlation (ρ = 0.369). In conclusion, teeth of this cohort were found to be lighter, less red and yellow than the skin. Teeth colour was not related to eye colour, but lighter teeth were found to be associated with lighter skins, and redder lateral incisors to lighter hair. Darker facial skins or yellower forehead areas were also associated with darker hair and vice versa. The clinical relevance of the study is that the investigated facial characteristics are inter-correlated weakly to moderately, and for this reason predicting the colour parameters of one facial characteristic by another would not be accurate, but helpful for a rough colour selection as associations show.

  13. Beta-papillomavirus DNA loads in hair follicles of immunocompetent people and organ transplant recipients.

    PubMed

    Weissenborn, Sönke; Neale, Rachel E; Waterboer, Tim; Abeni, Damiano; Bavinck, Jan Nico Bouwes; Green, Adele C; Harwood, Catherine A; Euvrard, Sylvie; Feltkamp, Mariet C W; de Koning, Maurits N C; Naldi, Luigi; Quint, Wim G V; Tessari, Gianpaolo; Proby, Charlotte M; Wieland, Ulrike; Pfister, Herbert

    2012-05-01

    There is increasing evidence of an association between human papillomaviruses (HPV) of the beta-genus (beta-PV) and the development of cutaneous squamous cell carcinoma (SCC). The viral DNA load may be an important determinant of pathogenicity, but there are currently no baseline epidemiological data relating to load in people without SCC. We investigated DNA-loads of eight beta-PV types previously associated with risk of SCC. We collected eyebrow hairs from immunocompetent people (ICP) and organ transplant recipients (OTR), determined load by quantitative PCR and obtained demographic, phenotypic, and sun exposure information. Viral loads for ICP from Australia (n = 241) and Italy (n = 223) and OTR from across Europe (n = 318) spanned seven orders of magnitude. The median loads for all types were below one viral DNA copy per 60 cells and were highest for HPV5, HPV8 and HPV20. None of the populations had consistently higher viral loads for all 8 types. However, a higher proportion of OTR were in the top deciles of viral load distributions for six of the eight beta-PV types examined. In a nested analysis of Italian OTR and ICP, this finding was significant for six beta-PV types and cumulative load. Increasing age was significantly associated with higher viral loads in Australia, and there was a weak trend for higher loads with the time elapsed since transplantation in the OTR. We observed a wide distribution of beta-PV loads with OTR significantly more likely to have the highest viral loads. Thus, viral loads may be an important contributor to the higher risk of SCC in OTR.

  14. Self-assembled polymeric nanocarriers for the targeted delivery of retinoic acid to the hair follicle

    NASA Astrophysics Data System (ADS)

    Lapteva, Maria; Möller, Michael; Gurny, Robert; Kalia, Yogeshvar N.

    2015-11-01

    Acne vulgaris is a highly prevalent dermatological disease of the pilosebaceous unit (PSU). An inability to target drug delivery to the PSU results in poor treatment efficacy and the incidence of local side-effects. Cutaneous application of nanoparticulate systems is reported to induce preferential accumulation in appendageal structures. The aim of this work was to prepare stable polymeric micelles containing retinoic acid (RA) using a biodegradable and biocompatible diblock methoxy-poly(ethylene glycol)-poly(hexylsubstituted lactic acid) copolymer (MPEG-dihexPLA) and to evaluate their ability to deliver RA to skin. An innovative punch biopsy sample preparation method was developed to selectively quantify follicular delivery; the amounts of RA present were compared to those in bulk skin, (i.e. without PSU), which served as the control. RA was successfully incorporated into micelle nanocarriers and protected from photoisomerization by inclusion of Quinoline Yellow. Incorporation into the spherical, homogeneous and nanometer-scale micelles (dn < 20 nm) increased the aqueous solubility of RA by >400-fold. Drug delivery experiments in vitro showed that micelles were able to deliver RA to porcine and human skins more efficiently than Retin-A® Micro (0.04%), a marketed gel containing RA loaded microspheres, (7.1 +/- 1.1% vs. 0.4 +/- 0.1% and 7.5 +/- 0.8% vs. 0.8 +/- 0.1% of the applied dose, respectively). In contrast to a non-colloidal RA solution, Effederm® (0.05%), both the RA loaded MPEG-dihexPLA polymeric micelles (0.005%) and Retin-A® Micro (0.04%) displayed selectivity for delivery to the PSU with 2-fold higher delivery to PSU containing samples than to control samples. Moreover, the micelle formulation outperformed Retin-A® Micro in terms of delivery efficiency to PSU presenting human skin (10.4 +/- 3.2% vs. 0.6 +/- 0.2%, respectively). The results indicate that the polymeric micelle formulation enabled an increased and targeted delivery of RA to the PSU

  15. Effect of oral intake of choline-stabilized orthosilicic acid on skin, nails and hair in women with photodamaged skin.

    PubMed

    Barel, A; Calomme, M; Timchenko, A; De Paepe, K; Paepe, K De; Demeester, N; Rogiers, V; Clarys, P; Vanden Berghe, D

    2005-10-01

    Chronic exposure of the skin to sunlight causes damage to the underlying connective tissue with a loss of elasticity and firmness. Silicon (Si) was suggested to have an important function in the formation and maintenance of connective tissue. Choline-stabilized orthosilicic acid ("ch-OSA") is a bioavailable form of silicon which was found to increase the hydroxyproline concentration in the dermis of animals. The effect of ch-OSA on skin, nails and hair was investigated in a randomized, double blind, placebo-controlled study. Fifty women with photodamaged facial skin were administered orally during 20 weeks, 10 mg Si/day in the form of ch-OSA pellets (n=25) or a placebo (n=25). Noninvasive methods were used to evaluate skin microrelief (forearm), hydration (forearm) and mechanical anisotropy (forehead). Volunteers evaluated on a virtual analog scale (VAS, "none=0, severe=3") brittleness of hair and nails. The serum Si concentration was significantly higher after a 20-week supplementation in subjects with ch-OSA compared to the placebo group. Skin roughness parameters increased in the placebo group (Rt:+8%; Rm: +11%; Rz: +6%) but decreased in the ch-OSA group (Rt: -16%; Rm: -19%; Rz: -8%). The change in roughness from baseline was significantly different between ch-OSA and placebo groups for Rt and Rm. The difference in longitudinal and lateral shear propagation time increased after 20 weeks in the placebo group but decreased in the ch-OSA group suggesting improvement in isotropy of the skin. VAS scores for nail and hair brittleness were significantly lower after 20 weeks in the ch-OSA group compared to baseline scores. Oral intake of ch-OSA during the 20 weeks results in a significant positive effect on skin surface and skin mechanical properties, and on brittleness of hair and nails.

  16. Acoustic absorption measurement of human hair and skin within the audible frequency range.

    PubMed

    Katz, B F

    2000-11-01

    Utilizing the two-microphone impedance tube method, the acoustic absorption of human skin and hair is measured in the frequency range 1-6 kHz. Various locations on a number of human subjects are measured to determine if the presence of bone or an air pocket affects the acoustic absorption of human skin. The absorption coefficient of human hair is also measured. Additional techniques are utilized to minimize errors due to sample mounting methods. Techniques are employed to minimize potential errors in sensor and sample locations. The results of these measurements are compared to relevant historical papers on similar investigations. Results for skin measurements compare well with previous work. Measured hair absorption data do not agree with previous work in the area but do coincide with expected trends, which previous works do not.

  17. iTRAQ-Based Quantitative Proteomic Comparison of Early- and Late-Passage Human Dermal Papilla Cell Secretome in Relation to Inducing Hair Follicle Regeneration

    PubMed Central

    Huang, Keng; Cai, Bo-Zhi; Zeng, Yang; Xu, Yan-Ming; Liu, Yang; Yuan, Yan-Ping; Lin, Chang-Min

    2016-01-01

    Alopecia is an exceedingly prevalent problem that lacks effective therapy. Recently, research has focused on early-passage dermal papilla cells (DPCs), which have hair inducing activity both in vivo and in vitro. Our previous study indicated that factors secreted from early-passage DPCs contribute to hair follicle (HF) regeneration. To identify which factors are responsible for HF regeneration and why late-passage DPCs lose this potential, we collected 48-h-culture medium (CM) from both of passage 3 and 9 DPCs, and subcutaneously injected the DPC-CM into NU/NU mice. Passage 3 DPC-CM induced HF regeneration, based on the emergence of a white hair coat, but passage 9 DPC-CM did not. In order to identify the key factors responsible for hair induction, CM from passage 3 and 9 DPCs was analyzed by iTRAQ-based quantitative proteomic technology. We identified 1360 proteins, of which 213 proteins were differentially expressed between CM from early-passage vs. late-passage DPCs, including SDF1, MMP3, biglycan and LTBP1. Further analysis indicated that the differentially-expressed proteins regulated the Wnt, TGF-β and BMP signaling pathways, which directly and indirectly participate in HF morphogenesis and regeneration. Subsequently, we selected 19 proteins for further verification by multiple reaction monitoring (MRM) between the two types of CM. These results indicate DPC-secreted proteins play important roles in HF regeneration, with SDF1, MMP3, biglycan, and LTBP1 being potential key inductive factors secreted by dermal papilla cells in the regeneration of hair follicles. PMID:27907131

  18. Induction of hair follicle dermal papilla cell properties in human induced pluripotent stem cell-derived multipotent LNGFR(+)THY-1(+) mesenchymal cells

    PubMed Central

    Veraitch, Ophelia; Mabuchi, Yo; Matsuzaki, Yumi; Sasaki, Takashi; Okuno, Hironobu; Tsukashima, Aki; Amagai, Masayuki; Okano, Hideyuki; Ohyama, Manabu

    2017-01-01

    The dermal papilla (DP) is a specialised mesenchymal component of the hair follicle (HF) that plays key roles in HF morphogenesis and regeneration. Current technical difficulties in preparing trichogenic human DP cells could be overcome by the use of highly proliferative and plastic human induced pluripotent stem cells (hiPSCs). In this study, hiPSCs were differentiated into induced mesenchymal cells (iMCs) with a bone marrow stromal cell phenotype. A highly proliferative and plastic LNGFR(+)THY-1(+) subset of iMCs was subsequently programmed using retinoic acid and DP cell activating culture medium to acquire DP properties. The resultant cells (induced DP-substituting cells [iDPSCs]) exhibited up-regulated DP markers, interacted with human keratinocytes to up-regulate HF related genes, and when co-grafted with human keratinocytes in vivo gave rise to fibre structures with a hair cuticle-like coat resembling the hair shaft, as confirmed by scanning electron microscope analysis. Furthermore, iDPSCs responded to the clinically used hair growth reagent, minoxidil sulfate, to up-regulate DP genes, further supporting that they were capable of, at least in part, reproducing DP properties. Thus, LNGFR(+)THY-1(+) iMCs may provide material for HF bioengineering and drug screening for hair diseases. PMID:28220862

  19. Double-stranded RNA induces inflammation via the NF-κB pathway and inflammasome activation in the outer root sheath cells of hair follicles

    PubMed Central

    Shin, Jung-Min; Choi, Dae-Kyoung; Sohn, Kyung-Cheol; Kim, Soo-Yeon; Min Ha, Jeong; Ho Lee, Young; Im, Myung; Seo, Young-Joon; Deok Kim, Chang; Lee, Jeung-Hoon; Lee, Young

    2017-01-01

    Alopecia areata (AA), a chronic, relapsing, hair-loss disorder, is considered to be a T cell-mediated autoimmune disease. It affects approximately 1.7% of the population, but its precise pathogenesis remains to be elucidated. Despite the recent attention focused on the roles of inflammasomes in the pathogenesis of autoinflammatory diseases, little is known about inflammasome activation in AA. Thus, in this study, we investigated the pattern of NLRP3 inflammasome activation in the outer root sheath (ORS) cells of hair follicles. We found that interleukin (IL)-1β and caspase-1 expression was increased in hair follicle remnants and inflammatory cells of AA tissue specimens. After stimulation of ORS cells with the double-stranded (ds)RNA mimic polyinosinic:polycytidylic acid (poly[I:C]), the activation of caspase-1 and secretion of IL-1β were enhanced. Moreover, NLRP3 knockdown decreased this poly(I:C)-induced IL-1β production. Finally, we found that high-mobility group box 1 (HMGB1) translocated from the nucleus to the cytosol and was secreted into the extracellular space by inflammasome activation. Taken together, these findings suggest that ORS cells are important immunocompetent cells that induce NLRP3 inflammasomes. In addition, dsRNA-induced IL-1β and HMGB1 secretion from ORS cells may contribute to clarifying the pathogenesis and therapeutic targets of AA. PMID:28266599

  20. Double-stranded RNA induces inflammation via the NF-κB pathway and inflammasome activation in the outer root sheath cells of hair follicles.

    PubMed

    Shin, Jung-Min; Choi, Dae-Kyoung; Sohn, Kyung-Cheol; Kim, Soo-Yeon; Min Ha, Jeong; Ho Lee, Young; Im, Myung; Seo, Young-Joon; Deok Kim, Chang; Lee, Jeung-Hoon; Lee, Young

    2017-03-07

    Alopecia areata (AA), a chronic, relapsing, hair-loss disorder, is considered to be a T cell-mediated autoimmune disease. It affects approximately 1.7% of the population, but its precise pathogenesis remains to be elucidated. Despite the recent attention focused on the roles of inflammasomes in the pathogenesis of autoinflammatory diseases, little is known about inflammasome activation in AA. Thus, in this study, we investigated the pattern of NLRP3 inflammasome activation in the outer root sheath (ORS) cells of hair follicles. We found that interleukin (IL)-1β and caspase-1 expression was increased in hair follicle remnants and inflammatory cells of AA tissue specimens. After stimulation of ORS cells with the double-stranded (ds)RNA mimic polyinosinic:polycytidylic acid (poly[I:C]), the activation of caspase-1 and secretion of IL-1β were enhanced. Moreover, NLRP3 knockdown decreased this poly(I:C)-induced IL-1β production. Finally, we found that high-mobility group box 1 (HMGB1) translocated from the nucleus to the cytosol and was secreted into the extracellular space by inflammasome activation. Taken together, these findings suggest that ORS cells are important immunocompetent cells that induce NLRP3 inflammasomes. In addition, dsRNA-induced IL-1β and HMGB1 secretion from ORS cells may contribute to clarifying the pathogenesis and therapeutic targets of AA.

  1. Scratching the surface of skin development

    PubMed Central

    Fuchs, Elaine

    2008-01-01

    The epidermis and its appendages develop from a single layer of multipotent embryonic progenitor keratinocytes. Embryonic stem cells receive cues from their environment that instruct them to commit to a particular differentiation programme and generate a stratified epidermis, hair follicles or sebaceous glands. Exciting recent developments have focused on how adult skin epithelia maintain populations of stem cells for use in the natural cycles of hair follicle regeneration and for re-epithelialization in response to wounding. PMID:17314969

  2. Hydroxyl radical mediates cisplatin-induced apoptosis in human hair follicle dermal papilla cells and keratinocytes through Bcl-2-dependent mechanism.

    PubMed

    Luanpitpong, Sudjit; Nimmannit, Ubonthip; Chanvorachote, Pithi; Leonard, Stephen S; Pongrakhananon, Varisa; Wang, Liying; Rojanasakul, Yon

    2011-08-01

    Induction of massive apoptosis of hair follicle cells by chemotherapy has been implicated in the pathogenesis of chemotherapy-induced alopecia (CIA), but the underlying mechanisms of regulation are not well understood. The present study investigated the apoptotic effect of cisplatin in human hair follicle dermal papilla cells and HaCaT keratinocytes, and determined the identity and role of specific reactive oxygen species (ROS) involved in the process. Treatment of the cells with cisplatin induced ROS generation and a parallel increase in caspase activation and apoptotic cell death. Inhibition of ROS generation by antioxidants inhibited the apoptotic effect of cisplatin, indicating the role of ROS in the process. Studies using specific ROS scavengers further showed that hydroxyl radical, but not hydrogen peroxide or superoxide anion, is the primary oxidative species responsible for the apoptotic effect of cisplatin. Electron spin resonance studies confirmed the formation of hydroxyl radicals induced by cisplatin. The mechanism by which hydroxyl radical mediates the apoptotic effect of cisplatin was shown to involve down-regulation of the anti-apoptotic protein Bcl-2 through ubiquitin-proteasomal degradation. Bcl-2 was also shown to have a negative regulatory role on hydroxyl radical. Together, our results indicate an essential role of hydroxyl radical in cisplatin-induced cell death of hair follicle cells through Bcl-2 regulation. Since CIA is a major side effect of cisplatin and many other chemotherapeutic agents with no known effective treatments, the knowledge gained from this study could be useful in the design of preventive treatment strategies for CIA through localized therapy without compromising the chemotherapy efficacy.

  3. Laser hair removal pearls.

    PubMed

    Tierney, Emily P; Goldberg, David J

    2008-03-01

    A number of lasers and light devices are now available for the treatment of unwanted hair. The goal of laser hair removal is to damage stem cells in the bulge of the follicle through the targeting of melanin, the endogenous chromophore for laser and light devices utilized to remove hair. The competing chromophores in the skin and hair, oxyhemoglobin and water, have a decreased absorption between 690 nm and 1000 nm, thus making this an ideal range for laser and light sources. Pearls of laser hair removal are presented in this review, focusing on four areas of recent development: 1 treatment of blond, white and gray hair; 2 paradoxical hypertrichosis; 3 laser hair removal in children; and 4 comparison of lasers and IPL. Laser and light-based technologies to remove hair represents one of the most exciting areas where discoveries by dermatologists have led to novel treatment approaches. It is likely that in the next decade, continued advancements in this field will bring us closer to the development of a more permanent and painless form of hair removal.

  4. 3-Deoxysappanchalcone Promotes Proliferation of Human Hair Follicle Dermal Papilla Cells and Hair Growth in C57BL/6 Mice by Modulating WNT/β-Catenin and STAT Signaling

    PubMed Central

    Kim, Young Eun; Choi, Hyung Chul; Lee, In-Chul; Yuk, Dong Yeon; Lee, Hyosung; Choi, Bu Young

    2016-01-01

    3-Deoxysappanchalcone (3-DSC) has been reported to possess anti-allergic, antiviral, anti-inflammatory and antioxidant activities. In the present study, we investigated the effects of 3-DSC on the proliferation of human hair follicle dermal papilla cells (HDPCs) and mouse hair growth in vivo. A real-time cell analyzer system, luciferase assay, Western blot and real-time polymerase chain reaction (PCR) were employed to measure the biochemical changes occurring in HDPCs in response to 3-DSC treatment. The effect of 3-DSC on hair growth in C57BL/6 mice was also examined. 3-DSC promoted the proliferation of HDPCs, similar to Tofacitinib, an inhibitor of janus-activated kinase (JAK). 3-DSC promoted phosphorylation of β-catenin and transcriptional activation of the T-cell factor. In addition, 3-DSC potentiated interleukin-6 (IL-6)-induced phosphorylation and subsequent transactivation of signal transducer and activator of transcription-3 (STAT3), thereby increasing the expression of cyclin-dependent kinase-4 (Cdk4), fibroblast growth factor (FGF) and vascular endothelial growth factor (VEGF). On the contrary, 3-DSC attenuated STAT6 mRNA expression and IL4-induced STAT6 phosphorylation in HDPCs. Finally, we observed that topical application of 3-DSC promoted the anagen phase of hair growth in C57BL/6 mice. 3-DSC stimulates hair growth possibly by inducing proliferation of follicular dermal papilla cells via modulation of WNT/β-catenin and STAT signaling. PMID:27795451

  5. Comparative Transcriptome Analysis of Raccoon Dog Skin to Determine Melanin Content in Hair and Melanin Distribution in Skin

    PubMed Central

    Du, Zhanyu; Huang, Kai; Zhao, Jiaping; Song, Xingchao; Xing, Xiumei; Wu, Qiong; Zhang, Linbo; Xu, Chao

    2017-01-01

    The raccoon dog (Nyctereutes procyonoides) is an important canid fur-bearing animal species worldwide. Chinese raccoon dogs that present a white mutation, especially those with a white coat. Exploring melanin biosynthesis in the hair and skin of raccoon dogs is important for understanding the survival and evolutionary mechanisms of them. In this study, we measured the content of melanin in the hair of two types of raccoon dog and generated stained slices of skin tissue. The results indicated that melanin biosynthesis occurs in the wild-type (W) and white-type (B) raccoon dog skin, although less melanin is produced in B skin. We then sequenced the skin transcriptomes of W and B, compared the similarities and differences in expressed genes. A comparison of the gene expression showed 60 up-regulated genes and 127 down-regulated genes in B skin. We analyzed the unigenes and pathways related to the melanogenesis pathway and found that TYR, TYRP1, MC1R, SLC24a5, SLC45a2 and OCA2 were significantly down-regulated in B skin and these results were verified via qRT-PCR. We surmised that the phenotypic characteristics of the white mutation might be caused by the reduced expression of these genes and this finding provides new insights for future experiments in raccoon dogs. PMID:28098220

  6. Melanocortin-1 receptor gene variants determine the risk of nonmelanoma skin cancer independently of fair skin and red hair.

    PubMed

    Bastiaens, M T; ter Huurne, J A; Kielich, C; Gruis, N A; Westendorp, R G; Vermeer, B J; Bavinck, J N

    2001-04-01

    Melanocortin-1 receptor (MC1R) gene variants are associated with fair skin and red hair and, independently of these, with cutaneous malignant melanoma. The association of MC1R gene variants with nonmelanoma skin cancer is largely unknown. A total of 838 subjects were included in the present study: 453 patients with nonmelanoma skin cancer and 385 subjects with no skin cancer. The coding sequence of the human MC1R gene was tested using single-stranded conformation polymorphism analysis followed by sequencing of unknown variants. Risk of skin cancer dependent on the various MC1R gene variants was estimated using the exposure odds ratio. We investigated whether subjects with MC1R variant alleles were at increased risk of developing nonmelanoma skin cancer and, if so, whether this increased risk was mediated by fair skin and red hair. A total of 27 MC1R gene variants were found. The number of carriers of one, two, or three MC1R gene variants was 379 (45.2%), 208 (24.8%), and 7 (0.9%), respectively. A strong association between MC1R gene variants and fair skin and red hair was established, especially the variants Arg151Cys and Arg160Trp (P < .0001). Carriers of two variant alleles were at increased risk for developing cutaneous squamous cell carcinoma (odds ratio 3.77; 95% confidence interval [CI] 2.11-6.78), nodular basal cell carcinoma (odds ratio 2.26; 95% CI 1.45-3.52), and superficial multifocal basal cell carcinoma (odds ratio 3.43; 95% CI 1.92-6.15), compared with carriers of two wild-type alleles. Carriers of one variant allele had half the risk. The highest relative risks of nonmelanoma skin cancer were found in carriers of the Asp84Glu, His260Pro, and Asp294His variant alleles, and the risk was only slightly lower for carriers of the Val60Leu, Val92Met, Arg142His, Arg151Cys, and Arg160Trp variant alleles. When subjects were stratified by skin type and hair color, analysis showed that these factors did not materially change the relative risks. These findings

  7. Hair Loss

    MedlinePlus

    ... over the scalp. This is a sign of ringworm. It may be accompanied by broken hair, redness, ... on the skin. Scalp infections. Infections, such as ringworm, can invade the hair and skin of your ...

  8. Hair Transplants

    MedlinePlus

    ... Stretch Marks Sun-damaged Skin Unwanted Hair Unwanted Tattoos Varicose Veins Vitiligo Wrinkles Treatments and Procedures Ambulatory ... Stretch Marks Sun-damaged Skin Unwanted Hair Unwanted Tattoos Varicose Veins Vitiligo Wrinkles Treatments and Procedures Ambulatory ...

  9. Minoxidil-containing dosage forms: skin retention and after-rinsing hair-growth promotion.

    PubMed

    Kim, Jin-Chul; Lee, Min-Ho; Rang, Moon-Jeong

    2003-01-01

    Three kinds of topical dosage forms of minoxidil (MXD), namely vesicles, double emulsions, and an inclusion complex with hydoxypropyl-beta-cyclodextrin (HP-beta-CD), were prepared. The skin retention of MXD in the preparations was evaluated in vitro using hairless mouse skins. After applying the preparations onto the skin and rinsing it, the amount of the drug left on the skin was determined using HPLC. Retention was the highest when the drug was encapsulated in cationic vesicles. Nonionic vehicle, the double emulsion, and HP-beta-CD left no significant amount of the drug after rinsing the skin. Thus, an ionic interaction between the cationic vehicle and negatively charged skin is likely responsible for the relatively high skin retention. In vivo hair growth-promotion effect of each dosage form was investigated, in which the sample application onto the clipped backs of female mice (C57BL6) and the subsequent rinsing of the backs were done once a day for 30 days. Only MXD in the cationic vesicles had hair growth promotion effect, possibly due to significant skin retention.

  10. In vivo regulation of murine hair growth: insights from grafting defined cell populations onto nude mice.

    PubMed

    Lichti, U; Weinberg, W C; Goodman, L; Ledbetter, S; Dooley, T; Morgan, D; Yuspa, S H

    1993-07-01

    The nude mouse graft model for testing the hair-forming ability of selected cell populations has considerable potential for providing insights into factors that are important for hair follicle development and proper hair formation. We have developed a minimal component system consisting of immature hair follicle buds from newborn pigmented C57BL/6 mice and adenovirus E1A-immortalized rat vibrissa dermal papilla cells. Hair follicle buds contribute to formation of hairless skin when grafted alone or with Swiss 3T3 cells, but produce densely haired skin when grafted with a fresh dermal cell preparation. The fresh dermal cell preparation represents the single cell fraction after hair follicles have been removed from a collagenase digest of newborn mouse dermis. It provides dermal papilla cells, fibroblasts, and possibly other important growth factor-producing cell types. Rat vibrissa dermal papilla cells supported dense hair growth at early passage in culture but progressively lost this potential during repeated passage in culture. Of 19 E1A-immortalized, clonally derived rat vibrissa dermal papilla cell lines, the four most positive clones supported hair growth to the extent of approximately 200 to 300 hairs per 1-2 cm2 graft area. The remaining clones were moderately positive (five clones), weakly positive (three clones), or negative (seven clones). Swiss 3T3 cells prevented contraction of the graft area but did not appear to affect the number of hairs in the graft site produced by dermal papilla cells plus hair follicle buds alone. The relatively low hair density (estimated 1-5% of normal) resulting from grafts of hair follicle buds with the most positive of the immortalized dermal papilla cell clones compared to fresh dermal cells suggests that optimal reconstitution of hair growth requires some function of dermal papilla cells partially lost during the immortalization process and possibly the contribution of other cell types present in the fresh dermal cell

  11. Effect of topical application of raspberry ketone on dermal production of insulin-like growth factor-I in mice and on hair growth and skin elasticity in humans.

    PubMed

    Harada, Naoaki; Okajima, Kenji; Narimatsu, Noriko; Kurihara, Hiroki; Nakagata, Naomi

    2008-08-01

    Sensory neurons release calcitonin gene-related peptide (CGRP) on activation. We recently reported that topical application of capsaicin increases facial skin elasticity and promotes hair growth by increasing dermal insulin-like growth factor-I (IGF-I) production through activation of sensory neurons in mice and humans. Raspberry ketone (RK), a major aromatic compound contained in red raspberries (Rubus idaeus), has a structure similar to that of capsaicin. Thus, it is possible that RK activates sensory neurons, thereby increasing skin elasticity and promoting hair growth by increasing dermal IGF-I production. In the present study, we examined this possibility in mice and humans. RK, at concentrations higher than 1 microM, significantly increased CGRP release from dorsal root ganglion neurons (DRG) isolated from wild-type (WT) mice and this increase was completely reversed by capsazepine, an inhibitor of vanilloid receptor-1 activation. Topical application of 0.01% RK increased dermal IGF-I levels at 30 min after application in WT mice, but not in CGRP-knockout mice. Topical application of 0.01% RK increased immunohistochemical expression of IGF-I at dermal papillae in hair follicles and promoted hair re-growth in WT mice at 4 weeks after the application. When applied topically to the scalp and facial skin, 0.01% RK promoted hair growth in 50.0% of humans with alopecia (n=10) at 5 months after application and increased cheek skin elasticity at 2 weeks after application in 5 females (p<0.04). These observations strongly suggest that RK might increase dermal IGF-I production through sensory neuron activation, thereby promoting hair growth and increasing skin elasticity.

  12. Comparative Transcriptome Analysis Reveals that a Ubiquitin-Mediated Proteolysis Pathway Is Important for Primary and Secondary Hair Follicle Development in Cashmere Goats

    PubMed Central

    Zheng, Zhu-qing; Fu, Shao-yin; Tarekegn, Getinet Mekuriaw; Bai, Xue; Bai, Yong-sheng; Li, Heng; Zhang, Wen-guang

    2016-01-01

    Background The fleece of cashmere goats contains two distinct populations of fibers, a short and fine non-medullated insulating cashmere fiber and a long and coarse medullated guard hair. The former is produced by secondary follicles (SFs) and the later by primary follicles (PFs). Evidence suggests that the induction of PFs and SFs may require different signaling pathways. The regulation of BMP2/4 signaling by noggin and Edar signaling via Downless genes are essential for the induction of SFs and PFs, respectively. However, these differently expressed genes of the signaling pathway cannot directly distinguish between the PFs and SFs. Results In this study, we selected RNA samples from 11 PFs and 7 SFs that included 145,525 exons. The pathway analysis of 4512 differentially expressed exons revealed that the most statistically significant metabolic pathway was related to the ubiquitin–mediated proteolysis pathway (UMPP) (P<3.32x 10−7). In addition, the 51 exons of the UMPP that were differentially expressed between the different types of hair follicle (HFs) were compared by cluster analysis. This resulted in the PFs and SFs being divided into two classes. The expression level of two selected exons was analyzed by qRT-PCR, and the results indicated that the expression patterns were consistent with the deep sequencing results obtained by RNA-Seq. Conclusions Based on the comparative transcriptome analysis of 18 HFs from cashmere goats, a large number of differentially expressed exons were identified using a high-throughput sequencing approach. This study suggests that UMPP activation is a prominent signaling pathway for distinguishing the PFs and SFs of cashmere goats. It is also a meaningful contribution to the theoretical basis of the biological study of the HFs of cashmere goats and other mammals. PMID:27695037

  13. An effective hair detection algorithm for dermoscopic melanoma images of skin lesions

    NASA Astrophysics Data System (ADS)

    Chakraborti, Damayanti; Kaur, Ravneet; Umbaugh, Scott; LeAnder, Robert

    2016-09-01

    Dermoscopic images are obtained using the method of skin surface microscopy. Pigmented skin lesions are evaluated in terms of texture features such as color and structure. Artifacts, such as hairs, bubbles, black frames, ruler-marks, etc., create obstacles that prevent accurate detection of skin lesions by both clinicians and computer-aided diagnosis. In this article, we propose a new algorithm for the automated detection of hairs, using an adaptive, Canny edge-detection method, followed by morphological filtering and an arithmetic addition operation. The algorithm was applied to 50 dermoscopic melanoma images. In order to ascertain this method's relative detection accuracy, it was compared to the Razmjooy hair-detection method [1], using segmentation error (SE), true detection rate (TDR) and false positioning rate (FPR). The new method produced 6.57% SE, 96.28% TDR and 3.47% FPR, compared to 15.751% SE, 86.29% TDR and 11.74% FPR produced by the Razmjooy method [1]. Because of the 7.27-9.99% improvement in those parameters, we conclude that the new algorithm produces much better results for detecting thick, thin, dark and light hairs. The new method proposed here, shows an appreciable difference in the rate of detecting bubbles, as well.

  14. Surface Tension Guided Hanging-Drop: Producing Controllable 3D Spheroid of High-Passaged Human Dermal Papilla Cells and Forming Inductive Microtissues for Hair-Follicle Regeneration.

    PubMed

    Lin, Bojie; Miao, Yong; Wang, Jin; Fan, Zhexiang; Du, Lijuan; Su, Yongsheng; Liu, Bingcheng; Hu, Zhiqi; Xing, Malcolm

    2016-03-09

    Human dermal papilla (DP) cells have been studied extensively when grown in the conventional monolayer. However, because of great deviation from the real in vivo three-dimensional (3D) environment, these two-dimensional (2D) grown cells tend to lose the hair-inducible capability during passaging. Hence, these 2D caused concerns have motivated the development of novel 3D culture techniques to produce cellular microtissues with suitable mimics. The hanging-drop approach is based on surface tension-based technique and the interaction between surface tension and gravity field that makes a convergence of liquid drops. This study used this technique in a converged drop to form cellular spheroids of dermal papilla cells. It leads to a controllable 3Dspheroid model for scalable fabrication of inductive DP microtissues. The optimal conditions for culturing high-passaged (P8) DP spheroids were determined first. Then, the morphological, histological and functional studies were performed. In addition, expressions of hair-inductive markers including alkaline phosphatase, α-smooth muscle actin and neural cell adhesion molecule were also analyzed by quantitative RT-PCR, immunostaining and immunoblotting. Finally, P8-DP microtissues were coimplanted with newborn mouse epidermal cells (EPCs) into nude mice. Our results indicated that the formation of 3D microtissues not only endowed P8-DP microtissues many similarities to primary DP, but also confer these microtissues an enhanced ability to induce hair-follicle (HF) neogenesis in vivo. This model provides a potential to elucidate the native biology of human DP, and also shows the promising for the controllable and scalable production of inductive DP cells applied in future follicle regeneration.

  15. Estrogens and aging skin

    PubMed Central

    Thornton, M. Julie

    2013-01-01

    Estrogen deficiency following menopause results in atrophic skin changes and acceleration of skin aging. Estrogens significantly modulate skin physiology, targeting keratinocytes, fibroblasts, melanocytes, hair follicles and sebaceous glands, and improve angiogenesis, wound healing and immune responses. Estrogen insufficiency decreases defense against oxidative stress; skin becomes thinner with less collagen, decreased elasticity, increased wrinkling, increased dryness and reduced vascularity. Its protective function becomes compromised and aging is associated with impaired wound healing, hair loss, pigmentary changes and skin cancer.   Skin aging can be significantly delayed by the administration of estrogen. This paper reviews estrogen effects on human skin and the mechanisms by which estrogens can alleviate the changes due to aging. The relevance of estrogen replacement, selective estrogen receptor modulators (SERMs) and phytoestrogens as therapies for diminishing skin aging is highlighted. Understanding estrogen signaling in skin will provide a basis for interventions in aging pathologies. PMID:24194966

  16. Hair follicles--an efficient storage and penetration pathway for topically applied substances. Summary of recent results obtained at the Center of Experimental and Applied Cutaneous Physiology, Charité -Universitätsmedizin Berlin, Germany.

    PubMed

    Lademann, J; Knorr, F; Richter, H; Blume-Peytavi, U; Vogt, A; Antoniou, C; Sterry, W; Patzelt, A

    2008-01-01

    In the past, it was assumed that the intercellular route was the only relevant penetration pathway for topically applied substances. Recent results on follicular penetration obtained at the Center for Experimental and Applied Cutaneous Physiology, Charité - Universitätsmedizin Berlin, Germany, emphasize that the hair follicles represent a highly relevant and efficient penetration pathway and reservoir for topically applied substances.

  17. Hair Growth Promotion Activity and Its Mechanism of Polygonum multiflorum

    PubMed Central

    Li, Yunfei; Han, Mingnuan; Lin, Pei; He, Yanran; Yu, Jie; Zhao, Ronghua

    2015-01-01

    Polygonum multiflorum Radix (PMR) has long history in hair growth promotion and hair coloring in clinical applications. However, several crucial problems in its clinic usage and mechanisms are still unsolved or lack scientific evidences. In this research, C57BL/6J mice were used to investigate hair growth promotion activity and possible mechanism of PMR and Polygonum multiflorum Radix Preparata (PMRP). Hair growth promotion activities were investigated by hair length, hair covered skin ratio, the number of follicles, and hair color. Regulation effects of several cytokines involved in the hair growth procedure were tested, such as fibroblast growth factor (FGF-7), Sonic Hedgehog (SHH), β-catenin, insulin-like growth factor-1 (IGF-1), and hepatocyte growth factor (HGF). Oral PMR groups had higher hair covered skin ratio (100 ± 0.00%) than oral PMRP groups (48%~88%). However, topical usage of PMRP had about 90% hair covered skin ratio. Both oral administration of PMR and topically given PMRP showed hair growth promotion activities. PMR was considered to be more suitable for oral administration, while PMRP showed greater effects in external use. The hair growth promotion effect of oral PMR was most probably mediated by the expression of FGF-7, while topical PMRP promoted hair growth by the stimulation of SHH expression. PMID:26294926

  18. Vitamin D3 analogs stimulate hair growth in nude mice.

    PubMed

    Vegesna, Vijaya; O'Kelly, James; Uskokovic, Milan; Said, Jonathan; Lemp, Nathan; Saitoh, Takayuki; Ikezoe, Takayuki; Binderup, Lise; Koeffler, H Phillip

    2002-11-01

    The active form of vitamin D3 can regulate epidermal keratinization by inducing terminal differentiation; and mice lacking the vitamin D receptor display defects leading to postnatal alopecia. These observations implicate the vitamin D3 pathway in regulation of hair growth. We tested the ability of 1,25 dihydroxyvitamin D3 and its synthetic analogs to stimulate hair growth in biege/nude/xid (BNX) nu/nu (nude) mice exhibiting congenital alopecia. Nude mice were treated with different vitamin D3 analogs at doses that we had previously found to be the highest dose without inducing toxicity (hypercalcemia). The mice were monitored for hair growth and were scored according to a defined scale. Skin samples were taken for histological observation of hair follicles and for extraction of RNA and protein. Vitamin D3 analogs dramatically stimulated the hair growth of nude mice, although parental 1,25 dihydroxyvitamin D3 had no effect. Hair growth occurred in a cyclical pattern, accompanied by formation of normal hair follicles and increased expression of certain keratins (Ha7, Ha8, and Hb3). Vitamin D3 analogs seem to act on keratinocytes to initiate hair follicle cycling and stimulate hair growth in mice that otherwise do not grow hair.

  19. Induction of Hair Growth by Insulin-Like Growth Factor-1 in 1,763 MHz Radiofrequency-Irradiated Hair Follicle Cells

    PubMed Central

    Jo, Seong Jin; Cho, A-Ri; Jeon, Soon-Ik; Choi, Hyung-Do; Kim, Kyu Han; Park, Gun-Sik; Pack, Jeong-Ki; Kwon, Oh Sang; Park, Woong-Yang

    2011-01-01

    Radiofrequency (RF) radiation does not transfer high energy to break the covalent bonds of macromolecules, but these low energy stimuli might be sufficient to induce molecular responses in a specific manner. We monitored the effect of 1,763 MHz RF radiation on cultured human dermal papilla cells (hDPCs) by evaluating changes in the expression of cytokines related to hair growth. The expression of insulin-like growth factor-1 (IGF-1) mRNA in hDPCs was significantly induced upon RF radiation at the specific absorption rate of 10 W/kg, which resulted in increased expression of B-cell chronic lymphocytic leukemia/lymphoma 2 (BCL-2) and cyclin D1 (CCND1) proteins and increased phosphorylation of MAPK1 protein. Exposure to 10 W/kg RF radiation 1 h per day for 7 days significantly enhanced hair shaft elongation in ex vivo hair organ cultures. In RF-exposed follicular matrix keratinocytes in the hair bulb, the expression of Ki-67 was increased, while the signal for terminal deoxynucleotidyl transferase dUTP nick end labeling was reduced. From these results, we suggest that 1,763 MHz RF exposure stimulates hair growth in vitro through the induction of IGF-1 in hDPCs. PMID:22164296

  20. Skin Dictionary

    MedlinePlus

    ... your skin, hair, and nails Skin dictionary Camp Discovery Good Skin Knowledge lesson plans and activities Video library Find a ... your skin, hair, and nails Skin dictionary Camp Discovery Good Skin Knowledge lesson plans and activities Video library Find a ...

  1. Use of silicon for skin and hair care: an approach of chemical forms available and efficacy*

    PubMed Central

    de Araújo, Lidiane Advincula; Addor, Flavia; Campos, Patrícia Maria Berardo Gonçalves Maia

    2016-01-01

    Silicon is the second most abundant element on Earth, and the third most abundant trace element in human body. It is present in water, plant and animal sources. On the skin, it is suggested that silicon is important for optimal collagen synthesis and activation of hydroxylating enzymes, improving skin strength and elasticity. Regarding hair benefits, it was suggested that a higher silicon content in the hair results in a lower rate of hair loss and increased brightness. For these beneficial effects, there is growing interest in scientific studies evaluating the efficacy and safety of using dietary supplements containing silicon. Its use aims at increasing blood levels of this element and improving the skin and its annexes appearance. There are different forms of silicon supplements available and the most important consideration to be made in order to select the best option is related to safety and bioavailability. Silicon supplements are widely used, though there is wide variation in silicon bioavailability, ranging from values below 1% up to values close to 50%, depending on the chemical form. Therefore, the aim of this study was to evaluate the scientific literature related to the different chemical forms of silicon supplements available and the limitations and recent progress in this field. According to reported studies, among the different chemical forms available, the orthosilicic acid (OSA) presents the higher bioavailability, whereas the others forms have absorption inversely proportional to the degree of polymerization. However, clinical studies evaluating safety and efficacy are still lacking. PMID:27438201

  2. In vivo Quantification of the Effects of Radiation and Presence of Hair Follicle Pores on the Proliferation of Fibroblasts in an Acellular Human Dermis in a Dorsal Skinfold Chamber: Relevance for Tissue Reconstruction following Neoadjuvant Therapy

    PubMed Central

    Maier, Patrick; Hohenberger, Peter; Roessner, Eric Dominic

    2015-01-01

    Introduction In neoadjuvant therapy, irradiation has a deleterious effect on neoangiogenesis. The aim of this study was to examine the post-implantation effects of neoadjuvant irradiation on the survival and proliferation of autologous cells seeded onto an acellular human dermis (hAD; Epiflex). Additionally, we examined the influence of dermal hair follicle pores on viability and proliferation. We used dorsal skinfold chambers implanted in rats and in-situ microscopy to quantify cell numbers over 9 days. Methods 24 rats received a skinfold chamber and were divided into 2 main groups; irradiated and unirradiated. In the irradiated groups 20Gy were applied epicutaneously at the dorsum. Epiflex pieces were cut to size 5x5mm such that each piece had either one or more visible hair follicle pores, or no such visible pores. Fibroblasts were transduced lentiviral with a fluorescent protein for cell tracking. Matrices were seeded statically with 2.5x104 fluorescent fibroblasts and implanted into the chambers. In each of the two main groups, half of the rats received Epiflex with hair follicle pores and half received Epiflex without pores. Scaffolds were examined in-situ at 0, 3, 6 and 9 days after transplantation. Visible cells on the surface were quantified using ImageJ. Results In all groups cell numbers were decreased on day 3. A treatment-dependent increase in cell numbers was observed at subsequent time points. Irradiation had an adverse effect on cell survival and proliferation. The number of cells detected in both irradiated and non-irradiated subjects was increased in those subjects that received transplants with hair follicle pores. Discussion This in-vivo study confirms that radiation negatively affects the survival and proliferation of fibroblasts seeded onto a human dermis transplant. The presence of hair follicle pores in the dermis transplants is shown to have a positive effect on cell survival and proliferation even in irradiated subjects. PMID:25955842

  3. Human white blood cells and hair follicles are good sources of mRNA for the pterin carbinolamine dehydratase/dimerization cofactor of HNF1 for mutation detection.

    PubMed

    Lei, X D; Kaufman, S

    1998-07-20

    Pterin carbinolamine dehydratase/dimerization cofactor of HNF1 (PCD/DCoH) is a protein that has a dual function. It is a pterin 4alpha-carbinolamine dehydratase that is involved in the regeneration of the cofactor tetrahydrobiopterin during the phenylalanine hydroxylase- catalyzed hydroxylation of phenylalanine. In addition, it is the dimerization cofactor of HNF1 that is able to activate the transcriptional activity of HNF1. Deficiencies in the gene for this dual functional protein result in hyperphenylalaninemia. Here we report for the first time that the PCD/DCoH mRNA is present in human white blood cells and hair follicles. Taking advantage of this finding, a sensitive, rapid and convenient method for screening mutations occurring in the coding region of this gene has been described.

  4. Hair growth in human split-thickness skin grafts transplanted onto nude rats: the role of cyclosporin.

    PubMed

    Gilhar, A; Etzioni, A; Krueger, G G

    1990-01-01

    To date, there have been no descriptions of hair growth following transplantation of human split-thickness skin grafts (HSTSG) to congenitally athymic (nude) mice or rats. Recently, we noted hair growth in HSTSG from scalp skin (HSTSG-SS) transplanted onto rats treated with ciclosporin (CS). By definition, HSTSG-SS of 0.4 mm had all the anagen hairs cut from the papillae. Two months after engraftment, there was histological evidence of the formation of new papillae. Density of hair correlated with thickness of HSTSG, i.e. there were more hairs/square centimeter in HSTSG-SS of 1 mm thickness than in those of 0.4 mm thickness. New hairs appeared on an average of 1 cm2/week in HSTSG-SS that were 1 mm thick; by 10 weeks, the mean density was 7.9 hairs/cm2. In the thinner grafts, the density was 3.5 hairs/cm2 (p less than 0.025). The rate of growth in the thicker grafts ranged from 0 to 0.25 mm/day, with an average of 0.1 mm/day. At 10 weeks after grafting, the hairs had a mean length of 4.4 mm in the thicker and 1.7 mm in the thinner grafts (p less than 0.001). The average diameter of the hair shafts was 0.05 mm at the various times tested. These observations identify a previously unrecognized process of hair growth and present an in vivo model to study human hair growth process, including the role of CS in hair growth.

  5. Plucked human hair shafts and biomolecular medical research.

    PubMed

    Schembri, Kevin; Scerri, Christian; Ayers, Duncan

    2013-10-31

    The hair follicle is a skin integument at the boundary between an organism and its immediate environment. The biological role of the human hair follicle has lost some of its ancestral importance. However, an indepth investigation of this miniorgan reveals hidden complexity with huge research potential. An essential consideration when dealing with human research is the awareness of potential harm and thus the absolute need not to harm--a rule aptly qualified by the Latin term "primum non nocere" (first do no harm). The plucked hair shaft offers such advantages. The use of stem cells found in hair follicles cells is gaining momentum in the field of regenerative medicine. Furthermore, current diagnostic and clinical applications of plucked hair follicles include their use as autologous and/or three-dimensional epidermal equivalents, together with their utilization as surrogate tissue in pharmacokinetic and pharmacodynamics studies. Consequently, the use of noninvasive diagnostic procedures on hair follicle shafts, posing as a surrogate molecular model for internal organs in the individual patient for a spectrum of human disease conditions, can possibly become a reality in the near future.

  6. Skin age testing criteria: characterization of human skin structures by 500 MHz MRI multiple contrast and image processing.

    PubMed

    Sharma, Rakesh

    2010-07-21

    Ex vivo magnetic resonance microimaging (MRM) image characteristics are reported in human skin samples in different age groups. Human excised skin samples were imaged using a custom coil placed inside a 500 MHz NMR imager for high-resolution microimaging. Skin MRI images were processed for characterization of different skin structures. Contiguous cross-sectional T1-weighted 3D spin echo MRI, T2-weighted 3D spin echo MRI and proton density images were compared with skin histopathology and NMR peaks. In all skin specimens, epidermis and dermis thickening and hair follicle size were measured using MRM. Optimized parameters TE and TR and multicontrast enhancement generated better MRI visibility of different skin components. Within high MR signal regions near to the custom coil, MRI images with short echo time were comparable with digitized histological sections for skin structures of the epidermis, dermis and hair follicles in 6 (67%) of the nine specimens. Skin % tissue composition, measurement of the epidermis, dermis, sebaceous gland and hair follicle size, and skin NMR peaks were signatures of skin type. The image processing determined the dimensionality of skin tissue components and skin typing. The ex vivo MRI images and histopathology of the skin may be used to measure the skin structure and skin NMR peaks with image processing may be a tool for determining skin typing and skin composition.

  7. Skin age testing criteria: characterization of human skin structures by 500 MHz MRI multiple contrast and image processing

    NASA Astrophysics Data System (ADS)

    Sharma, Rakesh

    2010-07-01

    Ex vivo magnetic resonance microimaging (MRM) image characteristics are reported in human skin samples in different age groups. Human excised skin samples were imaged using a custom coil placed inside a 500 MHz NMR imager for high-resolution microimaging. Skin MRI images were processed for characterization of different skin structures. Contiguous cross-sectional T1-weighted 3D spin echo MRI, T2-weighted 3D spin echo MRI and proton density images were compared with skin histopathology and NMR peaks. In all skin specimens, epidermis and dermis thickening and hair follicle size were measured using MRM. Optimized parameters TE and TR and multicontrast enhancement generated better MRI visibility of different skin components. Within high MR signal regions near to the custom coil, MRI images with short echo time were comparable with digitized histological sections for skin structures of the epidermis, dermis and hair follicles in 6 (67%) of the nine specimens. Skin % tissue composition, measurement of the epidermis, dermis, sebaceous gland and hair follicle size, and skin NMR peaks were signatures of skin type. The image processing determined the dimensionality of skin tissue components and skin typing. The ex vivo MRI images and histopathology of the skin may be used to measure the skin structure and skin NMR peaks with image processing may be a tool for determining skin typing and skin composition.

  8. Variations of scalp, pubic and axillary hair.

    PubMed

    Mistry, Sanchita; Chatterjee, Madhumati; Ghosh, Jyoti Ratan; Chakrabarti, Nirmal Kanti; Bandyopadhyay, Arup Ratan

    2012-01-01

    Hair examinations and comparisons conducted by forensic scientists often provide investigative and associative information. Apart from its length and its natural color, hair displays a morphologic diversity both macroscopically and microscopically. Pseudogenization of hair keratin gene inactivation highlights dramatic differences and is thought to be one of the strongest reasons for localization of hair in human. Therefore, humans have several different types of hair that can be classified depending on their body position and form. Size, angle of penetrance through the skin, embryological time of first appearance, and structural variations in the hair follicles are all taken into account when classifying hair types. However, the classification of differential types of hair quantitative traits in human is yet to be undertaken. An attempt has been made in the present study to understand the variation by using the histomorphological and quantitative variables of 540 hair strands (180 each scalp, axillary and pubic hair) of 18 adult Bengalee Hindu caste females. Apart from variation in histomorphological variables, quantitative variables regarding shaft and medulla diameter demonstrated variation in terms of being significantly higher (p < 0.05) in pubic hair compared to that of axillary and scalp hair. Therefore, the present study envisaged that variability in histomorphological and quantitative traits in different areas of human could be one of the important criteria for personal identification in forensic research.

  9. Hair growth-promoting effect of Carthamus tinctorius floret extract.

    PubMed

    Junlatat, Jintana; Sripanidkulchai, Bungorn

    2014-07-01

    The florets of Carthamus tinctorius L. have traditionally been used for hair growth promotion. This study aimed to examine the potential of hydroxysafflor yellow A-rich C. tinctorius extract (CTE) on hair growth both in vitro and in vivo. The effect of CTE on cell proliferation and hair growth-associated gene expression in dermal papilla cells and keratinocytes (HaCaT) was determined. In addition, hair follicles from mouse neonates were isolated and cultured in media supplemented with CTE. Moreover, CTE was applied topically on the hair-shaved skin of female C57BL/6 mice, and the histological profile of the skin was investigated. C. tinctorius floret ethanolic extract promoted the proliferation of both dermal papilla cells and HaCaT and significantly stimulated hair growth-promoting genes, including vascular endothelial growth factor and keratinocyte growth factor. In contrast, CTE suppressed the expression of transforming growth factor-β1 that is the hair loss-related gene. Furthermore, CTE treatment resulted in a significant increase in the length of cultured hair follicles and stimulated the growth of hair with local effects in mice. The results provided the preclinical data to support the potential use of CTE as a hair growth-promoting agent.

  10. Hair Growth Promoting Potential of Phospholipids Purified from Porcine Lung Tissues

    PubMed Central

    Choi, Seong-Hyun; Moon, Jeong-Su; Jeon, Byung-Suk; Jeon, Yeon-Jeong; Yoon, Byung-Il; Lim, Chang-Jin

    2015-01-01

    BP201, porcine lung tissue-derived phospholipids, consists of phosphatidylcholine as a major phospholipid species. BP201 promoted hair growth after application onto the shaved backs of BALB/c and C3H mice. Its effect was enhanced when applied together with minoxidil (MNX) in C3H mice. When the tissue specimens prepared from the shaved skins of BP201-treated and control mice were microscopically examined, the total numbers of hair follicles in both anagen and telogen phases of BP201-treated mice were significantly higher than those of control mice. The numbers of hair follicles in the anagen phase of BP201-treated mice were also higher than those of control mice. In combination with MNX, BP201 further increased the total number of hair follicles, but did not alter the percentage of hair follicles in the anagenic phase. BP201 also increased the proliferation of human hair follicle dermal papilla cells. Collectively, BP201 possesses hair growth promoting potential, which would suggest its use singly or in combination for hair growth products. PMID:25767686

  11. Quantitative risk assessment for skin sensitisation: consideration of a simplified approach for hair dye ingredients.

    PubMed

    Goebel, Carsten; Diepgen, Thomas L; Krasteva, Maya; Schlatter, Harald; Nicolas, Jean-Francois; Blömeke, Brunhilde; Coenraads, Pieter Jan; Schnuch, Axel; Taylor, James S; Pungier, Jacquemine; Fautz, Rolf; Fuchs, Anne; Schuh, Werner; Gerberick, G Frank; Kimber, Ian

    2012-12-01

    With the availability of the local lymph node assay, and the ability to evaluate effectively the relative skin sensitizing potency of contact allergens, a model for quantitative-risk-assessment (QRA) has been developed. This QRA process comprises: (a) determination of a no-expected-sensitisation-induction-level (NESIL), (b) incorporation of sensitization-assessment-factors (SAFs) reflecting variations between subjects, product use patterns and matrices, and (c) estimation of consumer-exposure-level (CEL). Based on these elements an acceptable-exposure-level (AEL) can be calculated by dividing the NESIL of the product by individual SAFs. Finally, the AEL is compared with the CEL to judge about risks to human health. We propose a simplified approach to risk assessment of hair dye ingredients by making use of precise experimental product exposure data. This data set provides firmly established dose/unit area concentrations under relevant consumer use conditions referred to as the measured-exposure-level (MEL). For that reason a direct comparison is possible between the NESIL with the MEL as a proof-of-concept quantification of the risk of skin sensitization. This is illustrated here by reference to two specific hair dye ingredients p-phenylenediamine and resorcinol. Comparison of these robust and toxicologically relevant values is therefore considered an improvement versus a hazard-based classification of hair dye ingredients.

  12. Novel collagen sponge reinforced with polyglycolic acid fiber produces robust, normal hair in murine hair reconstitution model.

    PubMed

    Itoh, M; Hiraoka, Y; Kataoka, K; Huh, N H; Tabata, Y; Okochi, H

    2004-01-01

    The hair reconstitution assay is a useful system for studying cell-cell and epithelial-mesenchymal interaction. The current method consists of transplantation of both epidermal and dermal cells, using a silicone chamber placed on an athymic nude mouse. However, because of leakage and tilting of the grafted cells, the rate and area of hair growth vary depending on the chamber. We modified this method by using a collagen sponge as a scaffold and compared two types of collagen sponges, each having different tensile strengths. A conventional collagen sponge disturbed normal hair follicle formation; in contrast, a collagen sponge containing polyglycolic acid (PGA) fiber supported proper restructuring of skin and hair follicles. These data suggested the usefulness of PGA fiber-containing collagen sponges for hair reconstitution in research and clinical applications.

  13. In vitro investigation of the follicular penetration of porcine ear skin using a nanoparticle-emulsion containing the antiseptic polihexanide In vitro investigation of the follicular penetration of porcine ear skin

    NASA Astrophysics Data System (ADS)

    Ulmer, M.; Patzelt, A.; Vergou, T.; Lademann, J.; Richter, H.; Kramer, A.; Müller, G.; Sterry, W.; Lange-Asschenfeldt, B.

    2012-05-01

    Earlier investigations regarding the distribution of the bacterial flora on the human skin demonstrate that the hair follicle acts as a bacterial reservoir, providing a quick source for secondary recontamination. These findings highlight the importance of the hair follicle as a target for modern antiseptics. In the present study, we have assessed the follicular penetration of a curcumin-labeled particle-associated antiseptic into porcine skin by laser scanning microscopy. Therefore, the follicular penetration depth of the curcumin-labeled particle-associated antiseptic was compared to the follicular penetration depth of curcumin-labeled particles without antiseptic. The investigation was performed in vitro using porcine skin biopsies. By superposition of the images acquired in the transmission and the fluorescent modus, it was possible to visualize the distribution of the fluorescent dye inside the hair follicles. Quantitative and qualitative results showed that both dispersions penetrated efficiently into the hair follicles. The average penetration depth of the particles with attached antiseptic polihexanide was significantly higher than that of particles without the attached antiseptic. Also, whilst very little sample preparation was needed, laser scanning microscopy was found to be an efficient tool to visualize the skin relief and in particular the hair follicle shaft and localize fluorescent markers within the skin tissue and hair follicles.

  14. Disrupted hair follicle activity in cattle grazing endophyte-infected tall fescue in the summer insulates core body temperatures

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Ergot alkaloids produced by an endophyte (Neotyphodium coenophialum) that infects most plants of tall fescue (Lolium arundinaceum) causes cattle to have rough hair coats during the summer and persistent vascular constriction that impedes heat dissipation via blood flow to peripheral tissues. Experi...

  15. Hair loss

    MedlinePlus

    ... continual hair pulling or scalp rubbing Radiation therapy Tinea capitis (ringworm of the scalp) Tumor of the ovary or ... a plucked hair Skin biopsy If you have ringworm on the scalp, you may be prescribed an ...

  16. The in vivo melanocytotoxicity and depigmenting potency of N-2,4-acetoxyphenyl thioethyl acetamide in the skin and hair.

    PubMed

    Jimbow, M; Marusyk, H; Jimbow, K

    1995-10-01

    It has been shown previously that N-acetyl-4-S-cysteaminylphenol (N-Ac-4-S-CAP) is a tyrosinase substrate and a potent depigmenting agent of dark skin and black hair. The present study evaluated the depigmenting potency of an acetyl derivative of N-Ac-4-S-CAP, N-2,4-acetoxyphenyl thioethyl acetamide (NAP-TEA) in the skin and hair. We tested for (i) in vitro metabolites in the skin after topical application, and (ii) in vivo depigmenting potency in the skin and hair. We found that NAP-TEA was stable in water, but was converted to N-Ac-4-S-CAP after topical application to human skin. Therefore, although NAP-TEA was not a tyrosinase substrate, it could react with tyrosinase after being converted to N-Ac-4-S-CAP by O-deacetylation in vivo. NAP-TEA produced marked depigmentation of dark skin (Yucatan pig) after daily topical application. When given by intraperitoneal injection, it resulted in complete loss of hair colour (white) grown at the epilated site in adult C57 black mice after daily administration for 10 days, and incomplete loss of coat colour (silver grey) in newborn C57 black mice after a single administration. The depigmentation of the skin and hair was reversible. Split-dopa preparation and electron microscopy indicated that this depigmentation is primarily related to (i) a marked decrease in the number of functioning melanocytes and melanized melanosomes, (ii) a decrease in the number of melanosomes transferred to keratinocytes, and (iii) selective degeneration/inactivation of melanocytes, and deposition of melanin-like material in the Golgi cisternae, coated vesicles and melanosomes, where tyrosinase is reported to be located. We propose the NAP-TEA is converted in vivo to N-Ac-4-S-CAP which, via interaction with tyrosinase, causes reversible depigmentation of the skin and hair.

  17. Nanomechanical properties of human skin and introduction of a novel hair indenter.

    PubMed

    Álvarez-Asencio, Rubén; Wallqvist, Viveca; Kjellin, Mikael; Rutland, Mark W; Camacho, Alejandra; Nordgren, Niklas; Luengo, Gustavo S

    2016-02-01

    The mechanical resistance of the stratum corneum, the outermost layer of skin, to deformation has been evaluated at different length scales using Atomic Force Microscopy. Nanomechanical surface mapping was first conducted using a sharp silicon tip and revealed that Young׳s modulus of the stratum corneum varied over the surface with a mean value of about 0.4GPa. Force indentation measurements showed permanent deformation of the skin surface only at high applied loads (above 4µN). The latter effect was further demonstrated using nanomechanical imaging in which the obtained depth profiles clearly illustrate the effects of increased normal force on the elastic/plastic surface deformation. Force measurements utilizing the single hair fiber probe supported the nanoindentation results of the stratum corneum being highly elastic at the nanoscale, but revealed that the lateral scale of the deformation determines the effective elastic modulus.This result resolves the fact that the reported values in the literature vary greatly and will help to understand the biophysics of the interaction of razor cut hairs that curl back during growth and interact with the skin.

  18. New strategies for preoperative skin antisepsis.

    PubMed

    Ulmer, Miriam; Lademann, Juergen; Patzelt, Alexa; Knorr, Fanny; Kramer, Axel; Koburger, Torsten; Assadian, Ojan; Daeschlein, Georg; Lange-Asschenfeldt, Bernhard

    2014-01-01

    During the past decades, encouraging progress has been made in the prevention of surgical site infections (SSI). However, as SSI still occur today, strategic prevention measures such as standardized skin antisepsis must be implemented and rigorously promoted. Recent discoveries in skin physiology necessitate the development of novel antiseptic agents and procedures in order to ameliorate their efficacy. In particular, alternate target structures in the skin need to be taken into consideration for the development of the next generation of antiseptics. Recent investigations have shown that a high number of microorganisms are located within and in the close vicinity of the hair follicles. This suggests that these structures are an important reservoir of bacterial growth and activity in human skin. To date, it has not been fully elucidated to what extent conventional liquid antiseptics sufficiently target the hair follicle-related microbial population. Modern technologies such as tissue-tolerable plasma (TTP) have been tested for their potential antiseptic efficiency by reducing the bacterial load in the skin and in the hair follicles. First experiments using liposomes to deliver antiseptics into the hair follicles have been evaluated for their potential clinical application. The present review evaluates these two innovative methods for their efficacy and applicability in preoperative skin antiseptics.

  19. The failure behavior of the anchorage of hairs during slow extraction.

    PubMed

    Roersma, M E; Douven, L F; Lefki, K; Oomens, C W

    2001-03-01

    Treatment of excessive hair growth is an important issue in both dermatological and cosmetic practice. In contrast to treatments with medication, most physical methods are treatments that focus on the hair follicle. To obtain insight in the failure behavior of the anchorage of hairs, hairs were extracted (in vitro) from pig skin at a speed of 0.1mm/s, one at a time. The pulling force and tweezers displacement were recorded. The extracted hairs were classified with respect to the phase in the growing cycle: anagen (growing phase), telogen (resting phase) or other (catagen phase or unable to determine). The anagen hairs showed a different relation between the tweezers displacement and the pulling force than the telogen hairs. Moreover, the maximum force that could be applied before a hair was extracted proved to be lower for anagen hairs than for telogen hairs (0.36N, 1.8N, respectively). The extracted hair length, defined as the part of the hair that had been embedded in the skin which was extracted, was higher for anagen hairs than for telogen hairs (4.8mm, 3.0mm, respectively). Removing proximal skin tissue and the embedded parts of the anagen hair (root) resulted in a change of the extraction curves. The results indicate that two phenomena play a role in the anchorage of anagen hairs. We have proposed a model for the extraction of an anagen hair that has been based on these results: first the interface between hair and skin that is located around the inner root sheath (IRS) starts to fail, followed by failing of the hair itself in the region where the hair keratinizes.

  20. Trichotillomania (hair pulling disorder), skin picking disorder, and stereotypic movement disorder: toward DSM-V.

    PubMed

    Stein, Dan J; Grant, Jon E; Franklin, Martin E; Keuthen, Nancy; Lochner, Christine; Singer, Harvey S; Woods, Douglas W

    2010-06-01

    In DSM-IV-TR, trichotillomania (TTM) is classified as an impulse control disorder (not classified elsewhere), skin picking lacks its own diagnostic category (but might be diagnosed as an impulse control disorder not otherwise specified), and stereotypic movement disorder is classified as a disorder usually first diagnosed in infancy, childhood, or adolescence. ICD-10 classifies TTM as a habit and impulse disorder, and includes stereotyped movement disorders in a section on other behavioral and emotional disorders with onset usually occurring in childhood and adolescence. This article provides a focused review of nosological issues relevant to DSM-V, given recent empirical findings. This review presents a number of options and preliminary recommendations to be considered for DSM-V: (1) Although TTM fits optimally into a category of body-focused repetitive behavioral disorders, in a nosology comprised of relatively few major categories it fits best within a category of motoric obsessive-compulsive spectrum disorders, (2) available evidence does not support continuing to include (current) diagnostic criteria B and C for TTM in DSM-V, (3) the text for TTM should be updated to describe subtypes and forms of hair pulling, (4) there are persuasive reasons for referring to TTM as "hair pulling disorder (trichotillomania)," (5) diagnostic criteria for skin picking disorder should be included in DSM-V or in DSM-Vs Appendix of Criteria Sets Provided for Further Study, and (6) the diagnostic criteria for stereotypic movement disorder should be clarified and simplified, bringing them in line with those for hair pulling and skin picking disorder.

  1. The role of melanin as protector against free radicals in skin and its role as free radical indicator in hair.

    PubMed

    Herrling, Thomas; Jung, Katinka; Fuchs, Jürgen

    2008-05-01

    Throughout the body, melanin is a homogenous biological polymer containing a population of intrinsic, semiquinone-like radicals. Additional extrinsic free radicals are reversibly photo-generated by UV and visible light. Melanin photochemistry, particularly the formation and decay of extrinsic radicals, has been the subject of numerous electron spin resonance (ESR) spectroscopy studies. Several melanin monomers exist, and the predominant monomer in a melanin polymer depends on its location within an organism. In skin and hair, melanin differs in content of eumelanin or pheomelanin. Its bioradical character and its susceptibility to UV irradiation makes melanin an excellent indicator for UV-related processes in both skin and hair. The existence of melanin in skin is strongly correlated with the prevention against free radicals/ROS generated by UV radiation. Especially in the skin melanin (mainly eumelanin) ensures the only natural UV protection by eliminating the generated free radicals/ROS. Melanin in hair can be used as a free radical detector for evaluating the efficacy of hair care products. The aim of this study was to investigate the suitability of melanin as protector of skin against UV generated free radicals and as free radical indicator in hair.

  2. The role of melanin as protector against free radicals in skin and its role as free radical indicator in hair

    NASA Astrophysics Data System (ADS)

    Herrling, Thomas; Jung, Katinka; Fuchs, Jürgen

    2008-05-01

    Throughout the body, melanin is a homogenous biological polymer containing a population of intrinsic, semiquinone-like radicals. Additional extrinsic free radicals are reversibly photo-generated by UV and visible light. Melanin photochemistry, particularly the formation and decay of extrinsic radicals, has been the subject of numerous electron spin resonance (ESR) spectroscopy studies. Several melanin monomers exist, and the predominant monomer in a melanin polymer depends on its location within an organism. In skin and hair, melanin differs in content of eumelanin or pheomelanin. Its bioradical character and its susceptibility to UV irradiation makes melanin an excellent indicator for UV-related processes in both skin and hair. The existence of melanin in skin is strongly correlated with the prevention against free radicals/ROS generated by UV radiation. Especially in the skin melanin (mainly eumelanin) ensures the only natural UV protection by eliminating the generated free radicals/ROS. Melanin in hair can be used as a free radical detector for evaluating the efficacy of hair care products. The aim of this study was to investigate the suitability of melanin as protector of skin against UV generated free radicals and as free radical indicator in hair.

  3. Evaluation of pH of Bathing Soaps and Shampoos for Skin and Hair Care

    PubMed Central

    Tarun, Jose; Susan, Jose; Suria, Jacob; Susan, Veronica John; Criton, Sebastian

    2014-01-01

    Background: Normal healthy skin has potential of hydrogen (pH) range of 5.4-5.9 and a normal bacterial flora. Use of soap with high pH causes an increase in skin pH, which in turn causes an increase in dehydrative effect, irritability and alteration in bacterial flora. The majority of soaps and shampoos available in the market do not disclose their pH. Aims and Objectives: The aim of this study was to assess the pH of different brands of bathing soaps and shampoos available in the market. Materials and Methods: The samples of soaps and shampoos were collected from shops in the locality. The samples of different brands are coded before the analysis of the pH. Solution of each sample was made and pH was measured using pH meter. Results: Majority of the soaps have a pH within the range of 9-10. Majority of the shampoos have a pH within the range of 6-7. Conclusions: The soaps and shampoos commonly used by the population at large have a pH outside the range of normal skin and hair pH values. Therefore, it is hoped that before recommending soap to patient especially those who have sensitive and acne prone skin, due consideration is given to the pH factor and also that manufacturers will give a thought to pH of soaps and shampoos manufactured by them, so that their products will be more skin and hair friendly. PMID:25284846

  4. Short communication: Removal of hair from the mammary gland: Recovery of bacteria from teat skin and milk.

    PubMed

    Fox, L K

    2016-02-01

    It has been assumed that the presence of udder hair can interfere with safe milking practices and reduce the wholesomeness of milk relative to bacterial content. This study determined the effect of removal by singeing udder hair on the microflora of teat skin (total bacteria, coliform, and esculin-positive and esculin-negative streptococci) and milk (total bacteria, coliform, psychrotrophic, and thermoduric counts) as opposed to not singeing udder hair, using different pre-and postmilking disinfection (predip, postdip, or both) combinations. The 4 different pre-and postmilking disinfection combinations were predip and postdip, postdip only, predip only, and no predip and no postdip. Differences in bacterial numbers recovered from teat skin and milk in singed and not singed glands were not significantly affected by treatment. Findings of this trial do not support the concept that udder hair removal results in improved milk quality as measured by bacterial content.

  5. Genome-Wide Association Studies of Quantitatively Measured Skin, Hair, and Eye Pigmentation in Four European Populations

    PubMed Central

    Candille, Sophie I.; Absher, Devin M.; Beleza, Sandra; Bauchet, Marc; McEvoy, Brian; Garrison, Nanibaa’ A.; Li, Jun Z.; Myers, Richard M.; Barsh, Gregory S.; Tang, Hua; Shriver, Mark D.

    2012-01-01

    Pigmentation of the skin, hair, and eyes varies both within and between human populations. Identifying the genes and alleles underlying this variation has been the goal of many candidate gene and several genome-wide association studies (GWAS). Most GWAS for pigmentary traits to date have been based on subjective phenotypes using categorical scales. But skin, hair, and eye pigmentation vary continuously. Here, we seek to characterize quantitative variation in these traits objectively and accurately and to determine their genetic basis. Objective and quantitative measures of skin, hair, and eye color were made using reflectance or digital spectroscopy in Europeans from Ireland, Poland, Italy, and Portugal. A GWAS was conducted for the three quantitative pigmentation phenotypes in 176 women across 313,763 SNP loci, and replication of the most significant associations was attempted in a sample of 294 European men and women from the same countries. We find that the pigmentation phenotypes are highly stratified along axes of European genetic differentiation. The country of sampling explains approximately 35% of the variation in skin pigmentation, 31% of the variation in hair pigmentation, and 40% of the variation in eye pigmentation. All three quantitative phenotypes are correlated with each other. In our two-stage association study, we reproduce the association of rs1667394 at the OCA2/HERC2 locus with eye color but we do not identify new genetic determinants of skin and hair pigmentation supporting the lack of major genes affecting skin and hair color variation within Europe and suggesting that not only careful phenotyping but also larger cohorts are required to understand the genetic architecture of these complex quantitative traits. Interestingly, we also see that in each of these four populations, men are more lightly pigmented in the unexposed skin of the inner arm than women, a fact that is underappreciated and may vary across the world. PMID:23118974

  6. Genome-wide association studies of quantitatively measured skin, hair, and eye pigmentation in four European populations.

    PubMed

    Candille, Sophie I; Absher, Devin M; Beleza, Sandra; Bauchet, Marc; McEvoy, Brian; Garrison, Nanibaa' A; Li, Jun Z; Myers, Richard M; Barsh, Gregory S; Tang, Hua; Shriver, Mark D

    2012-01-01

    Pigmentation of the skin, hair, and eyes varies both within and between human populations. Identifying the genes and alleles underlying this variation has been the goal of many candidate gene and several genome-wide association studies (GWAS). Most GWAS for pigmentary traits to date have been based on subjective phenotypes using categorical scales. But skin, hair, and eye pigmentation vary continuously. Here, we seek to characterize quantitative variation in these traits objectively and accurately and to determine their genetic basis. Objective and quantitative measures of skin, hair, and eye color were made using reflectance or digital spectroscopy in Europeans from Ireland, Poland, Italy, and Portugal. A GWAS was conducted for the three quantitative pigmentation phenotypes in 176 women across 313,763 SNP loci, and replication of the most significant associations was attempted in a sample of 294 European men and women from the same countries. We find that the pigmentation phenotypes are highly stratified along axes of European genetic differentiation. The country of sampling explains approximately 35% of the variation in skin pigmentation, 31% of the variation in hair pigmentation, and 40% of the variation in eye pigmentation. All three quantitative phenotypes are correlated with each other. In our two-stage association study, we reproduce the association of rs1667394 at the OCA2/HERC2 locus with eye color but we do not identify new genetic determinants of skin and hair pigmentation supporting the lack of major genes affecting skin and hair color variation within Europe and suggesting that not only careful phenotyping but also larger cohorts are required to understand the genetic architecture of these complex quantitative traits. Interestingly, we also see that in each of these four populations, men are more lightly pigmented in the unexposed skin of the inner arm than women, a fact that is underappreciated and may vary across the world.

  7. Comparison of high-intensity ultraviolet and NB-UVB on the maturation of melanocytes derived from hair follicle neural crest stem cells.

    PubMed

    Dong, Dake; Chen, Shujun; Zhang, Xiaoli; Jin, Cheng; Zheng, Yuan; Yang, Lijia

    2014-09-01

    Both high-intensity ultraviolet and narrowband ultraviolet B (NB-UVB) are important therapeutic options for vitiligo management, but high-intensity ultraviolet is more effective than NB-UVB. However, the underlying mechanisms have not been well investigated. Herein, we compare the effects of high-intensity ultraviolet and NB-UVB on the pigmentation of melanocytes derived from hair follicle-derived neural crest stem cells (HF-NCSCs) in vitro and study the underlying mechanisms. The HF-NCSCs were isolated from mouse whisker follicles. After radiation with high-intensity ultraviolet and NB-UVB, respectively, the cell viability by the CCK-8 assay showed gradual inhibitory effects in a dose-dependent manner, which has no apparent difference between the two modalities. The mRNA for melanogenesis factors such as tyrosinase and tyrp1 of the differentiated melanocytes increased significantly with high-intensity ultraviolet compared to the same dose of NB-UVB exposure. Furthermore, the expression of Mc1r was significantly increased by high-intensity ultraviolet in contrast to NB-UVB at the dosage of 0.5 J. By and large, these data suggest that high-intensity ultraviolet exhibited greater efficiency on the maturation of the melanocyte lineage differentiated from HF-NCSCs compared to NB-UVB with the same dose, which was probably due to the stronger stimulatory action of Mc1r. This may provide new insights into the different efficacies of high-intensity ultraviolet and NB-UVB in the treatment of vitiligo repigmentation.

  8. Pharmacologic inhibition of JAK-STAT signaling promotes hair growth.

    PubMed

    Harel, Sivan; Higgins, Claire A; Cerise, Jane E; Dai, Zhenpeng; Chen, James C; Clynes, Raphael; Christiano, Angela M

    2015-10-01

    Several forms of hair loss in humans are characterized by the inability of hair follicles to enter the growth phase (anagen) of the hair cycle after being arrested in the resting phase (telogen). Current pharmacologic therapies have been largely unsuccessful in targeting pathways that can be selectively modulated to induce entry into anagen. We show that topical treatment of mouse and human skin with small-molecule inhibitors of the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway results in rapid onset of anagen and subsequent hair growth. We show that JAK inhibition regulates the activation of key hair follicle populations such as the hair germ and improves the inductivity of cultured human dermal papilla cells by controlling a molecular signature enriched in intact, fully inductive dermal papillae. Our findings open new avenues for exploration of JAK-STAT inhibition for promotion of hair growth and highlight the role of this pathway in regulating the activation of hair follicle stem cells.

  9. The mouse hairy ears mutation exhibits an extended growth (anagen) phase in hair follicles and altered Hoxc gene expression in the ears

    PubMed Central

    Mentzer, Sarah E.; Sundberg, John P.; Awgulewitsch, Alexander; Chao, Hanna HJ.; Carpenter, Donald A.; Zhang, Wei-Dong; Rinchik, Eugene M.; You, Yun

    2010-01-01

    The mouse In(15)2Rl (hairy ears, Eh) mutation is a paracentric inversion of the distal half of Chromosome 15 (Chr 15). Heterozygous Eh/+ mice display mis-shaped and hairy ears that have more and longer hair than the ears of their wild-type littermates. We mapped, cloned, and sequenced both inversion breakpoints. No protein-coding transcript was disrupted by either breakpoint. The proximal breakpoint is located between syntrophin basic 1 (Sntb1) and hyaluronan synthase 2 (Has2), and the distal breakpoint maps between homeobox C4 (Hoxc4) and single-strand selective monofunctional uracil DNA glycosylase (Smug1), near the middle and the telomere ends of Chr 15, respectively. The inversion spans ~47 Megabases (Mb). Our genetic analysis suggests that the hairy-ear phenotype is caused by the proximal breakpoint of the inversion-bearing Chr 15. Quantitative RNA analysis by RT-PCR for the genes flanking the breakpoint indicated no changes in expression levels except for some homeobox C (Hoxc) genes whose expression was elevated in developing and mature skin of the ears but not of other body regions. The increased hair length on the ears of Eh/+ mice was due to an extension of the anagen stage in the hair cycle, as determined by histological analysis. Our data indicate that the Eh phenotype arises from mis-expression of Hoxc genes. PMID:19037915

  10. Preparation and evaluation of a hair wax containing propolis and Eruca sativa seed oil for hair growth

    PubMed Central

    Shatalebi, Mohammad-Ali; Safaeian, Leila; Baradaran, Azar; Alamdarian, Mozhde

    2016-01-01

    Background: Hair growth as a key consumer objective has important role in the hair care products researches. This study was aimed to investigate the effect of a hair wax containing propolis, a resinous mixture produced by honeybees in Eruca sativa seed oil base on hair growth. Materials and Methods: The hair wax was designed and formulated compared with marketed brand hair wax and evaluated for pharmaceutical parameters including pH, homogeneity, consistency, spread ability, in vitro drug release, and stability. After selection of the best formulation containing 10% ethanolic extract of propolis and 10% E. sativa seed oil, the hair growth potential was evaluated by application of 1 g hair wax daily on 4 cm2 area of dorsal side of Wistar rats and compared with controls and standard medication (1 ml of 2% minoxidil). After 30 days treatment, the length and weight of hairs and percentage of hair follicles in different phases of growth in skin biopsies were assessed. Results: The selected hair wax formulation was stable and easy to wash. The formulation significantly increased hair length on 10th, 20th, and 30th day compared control group (5.8 ± 0.3 vs. 2.6 ± 0.4, 11.4 ± 0.6 vs. 5.8 ± 0.4, and 17.5 ± 0.5 vs. 12.7 ± 0.4 mm, respectively) and also the weight of newly grown hairs on 30th day (0.056 ± 0.006 vs. 0.043 ± 0.005). It improved hair follicles percentages in anagen phase without any sensitivity reaction. Conclusions: The results of this study suggest that the formulated hair wax containing of propolis and E. sativa seed oil could have significant effect on promoting hair growth. PMID:28028522

  11. Roles of GasderminA3 in catagen- telogen transition during hair cycling

    PubMed Central

    Bai, Xiufeng; Lei, Mingxing; Shi, Jiazhong; Yu, Yu; Qiu, Weiming; Lai, Xiangdong; Liu, Yingxin; Yang, Tian; Yang, Li; Widelitz, Randall Bruce; Chuong, Cheng-Ming; Lian, Xiaohua

    2015-01-01

    Hair follicles undergo cyclic behavior through regression (catagen), rest (telogen) and regeneration (anagen) during postnatal life. The hair cycle transition is strictly regulated by the autonomous and extrinsic molecular environment. However, whether there is a switch controlling catagen-telogen transition remains largely unknown. Here we show that hair follicles cycle from catagen to the next anagen without transitioning through a morphologically typical telogen after Gsdma3 mutation. This leaves an ESLS (epithelial strand-like structure) during the time period corresponding to telogen phase in WT mice. Molecularly, Wnt10b is upregulated in Gsdma3 mutant mice. Restoration of Gsdma3 expression in AE (alopecia and excoriation) mouse skin rescues hair follicle telogen entry and significantly decreases the Wnt10b-mediated Wnt/β-catenin signaling pathway. Overexpression of Wnt10b inhibits telogen entry by increasing epithelial strand cell proliferation. Subsequently, hair follicles with a Gsdma3 mutation enter the second anagen simultaneously as WT mice. Hair follicles cannot enter the second anagen with ectopic WT Gsdma3 overexpression. A luciferase reporter assay proves Gsdma3 directly suppresses Wnt signaling. Our findings suggest Gsdma3 plays an important role in catagen-telogen transition by balancing the Wnt signaling pathway, and that morphologically typical telogen is not essential for the initiation of a new hair cycle. PMID:25860385

  12. Vitamin D(3) synthesis in the entire skin surface of dairy cows despite hair coverage.

    PubMed

    Hymøller, L; Jensen, S K

    2010-05-01

    How hair-coated animals such as dairy cows synthesize endogenous vitamin D(3) during exposure to summer sunlight has been unclear since vitamin D(3) and its relation to sunlight was discovered. The fur of fur-bearing animals is thought to be comparable to clothing in humans, which prevents vitamin D(3) synthesis in the skin during exposure to sunlight. Different scenarios have been suggested but never tested in cows; for example, that vitamin D(3) is synthesized from sebum on the hair and ingested by cows during grooming or that body areas such as the udder and muzzle that have scant hair exclusively produce the vitamin. To test different scenarios, 16 Danish Holstein dairy cows were subjected to 4 degrees of coverage of their bodies with fabric that prevented vitamin D(3) synthesis in the covered skin areas. The treatments were horse blanket (cows fitted with horse blankets), udder cover (cows fitted with udder covers, horse blanket+udder cover (cows fitted with both horse blankets and udder covers), and natural (cows without any coverage fitted). The cows were let out to pasture daily between 1000 and 1500h for 4 wk in July and August 2009. Blood samples were collected 15 times during the study and analyzed for content of 25-hydroxyvitamin D(3) [25(OH)D(3)] indicative of the animals' vitamin D(3) status. Results showed that uncovered cows had a higher 25(OH)D(3) concentration in plasma after 28 d of access to sunlight compared with covered cows and that the plasma concentration of 25(OH)D(3) was strongly inversely correlated to the body surface area covered. These results are consistent with findings in humans, wherein the vitamin D(3) status of different individuals was inversely proportional to the amount of clothing worn during exposure to artificial sunlight. Hence, it appears that human clothing and cow hair are not comparable with respect to prevention of vitamin D(3) synthesis and that cows, like humans, synthesize vitamin D(3) evenly over their body

  13. Idiopathic hirsutism: excessive bodily and facial hair in women.

    PubMed

    Elghblawi, Ebtisam

    Hirsutism is the excessive and increased bodily and facial hair growth in women in locations where hair is normally minimal or absent. It refers to the growth of hair in a pattern normally occurring only in men, and therefore primarily raises psychological, cosmetic and social concerns. Idiopathic hirsutism (IH), where the cause of excessive hair growth is unknown, is considered to be the most common form of hirsutism. It is suspected that this type of hirsutism may be familial, as there is often a family history of the condition. Women with IH will generally have normal menses and normal levels of testosterone. There are many treatment modalities that fall into two broad groups: medical and mechanical treatment. An example of a medical treatment is when an agent is used, which interferes with the synthesis of androgen at the ovarian or adrenal level, or by inhibiting the effect of androgen at the receptor level. An example of a mechanical treatment is laser hair removal, where the hair follicle is destroyed; however, much depends on the on the skill of the treating practitioner, laser type, laser spot size, skin type, hair colour, and the stage at which the hair follicles were during their hair growth cycle, and the delivered wavelength. Laser offers the fastest method of hair loss. Other mechanical treatments include electrolysis, depilatory creams, plucking and waxing. This article presents a general overview of IH, including a definition, diagnostic measures, clinical manifestations, normal and abnormal physiology, and treatment options.

  14. Five-year incidence of age-related maculopathy in relation to iris, skin or hair colour, and skin sun sensitivity: the Blue Mountains Eye Study.

    PubMed

    Wang, Jie Jin; Jakobsen, Kirsten; Smith, Wayne; Mitchell, Paul

    2003-08-01

    This study aimed to assess longitudinal associations between iris,hair and skin colour, plus skin sensitivity to sun and the 5-year incidence of age-related maculopathy (ARM). Of 3654 baseline Blue Mountains Eye Study participants (aged 49+ years), 2335 survivors (75.1%) were re-examined after 5 years. Retinal photographs were graded using the Wisconsin ARM Grading System and incident ARM lesions confirmed using side-by-side grading.Iris/skin/hair colour was assessed and skin sensitivity questions were asked at baseline. After adjusting for age, sex and smoking, no significant associations were found between iris or hair colour and incident late or early ARM. Compared to persons with fair skin, those with very fair skin had an increased risk of developing geographical atrophy (odds ratio [OR] 3.5,95% confidence interval [CI] 1.2-10.4).However, persons with sun-related skin damage were less likely than those without to develop indistinct soft drusen (OR 0.6, 95% CI 0.4-0.9). Longitudinal data provide no support for the previously reported cross-sectional association between iris colour and ARM.

  15. Long-pulsed Nd:YAG laser-assisted hair removal in Fitzpatrick skin types IV-VI.

    PubMed

    Rao, Krishna; Sankar, Thangasamy K

    2011-09-01

    Unwanted hair is a common problem for which a variety of laser treatments is available. Laser treatment in dark-skinned individuals carries a higher risk of complications like hyperpigmentation and burn. The objective of this study was to evaluate efficacy and safety profile of laser-assisted hair removal in individuals with Fitzpatrick type IV-VI skin using long-pulsed Nd:YAG laser. Retrospective data was collected from 150 individuals with Fitzpatrick type IV-VI skin who underwent laser-assisted hair removal. This included area treated, fluence, number of treatments, and outcome. Data was also gathered on patient satisfaction and complications. The most common phototype was type IV (94%). The most frequently treated area was the face (84.7%) followed by the underarms and legs. Among the facial areas, the chin was the most frequently treated area followed by the upper lip and jaw line. The mean number of treatments was 8.9 (range 4-22). The maximum fluence averaged 26.8 Joules/cm(2) and was significantly higher for facial hair. Of the patients, 78.7% felt that their treatment was good or satisfactory. Mean hair reduction was 54.3%. Satisfaction from the treatment was significantly higher in individuals undergoing treatment of non-facial areas. Subsequent hair growth was slower and finer in 79.3% of the patients. There were no complications in 86% of the patients. All the complications were transient, with hyperpigmentation being the most frequent complication. Our results show that laser hair removal using the long-pulsed Nd:YAG laser is safe and effective in dark-skinned individuals with satisfactory results in most patients.

  16. Disruption of FGF5 in Cashmere Goats Using CRISPR/Cas9 Results in More Secondary Hair Follicles and Longer Fibers

    PubMed Central

    Zhu, Haijing; Niu, Yiyuan; Ma, Baohua; Yu, Honghao; Lei, Anmin; Yan, Hailong; Shen, Qiaoyan; Shi, Lei; Zhao, Xiaoe; Hua, Jinlian; Huang, Xingxu; Qu, Lei; Chen, Yulin

    2016-01-01

    Precision genetic engineering accelerates the genetic improvement of livestock for agriculture and biomedicine. We have recently reported our success in producing gene-modified goats using the CRISPR/Cas9 system through microinjection of Cas9 mRNA and sgRNAs targeting the MSTN and FGF5 genes in goat embryos. By investigating the influence of gene modification on the phenotypes of Cas9-mediated goats, we herein demonstrate that the utility of this approach involving the disruption of FGF5 results in increased number of second hair follicles and enhanced fiber length in Cas9-mediated goats, suggesting more cashmere will be produced. The effects of genome modifications were characterized using H&E and immunohistochemistry staining, quantitative PCR, and western blotting techniques. These results indicated that the gene modifications induced by the disruption of FGF5 had occurred at the morphological and genetic levels. We further show that the knockout alleles were likely capable of germline transmission, which is essential for goat population expansion. These results provide sufficient evidences of the merit of using the CRISPR/Cas9 approach for the generation of gene-modified goats displaying the corresponding mutant phenotypes. PMID:27755602

  17. Self-assembly of dermal papilla cells into inductive spheroidal microtissues on poly(ethylene-co-vinyl alcohol) membranes for hair follicle regeneration.

    PubMed

    Young, Tai-Horng; Lee, Chiao-Yun; Chiu, Hsien-Ching; Hsu, Chih-Jung; Lin, Sung-Jan

    2008-09-01

    Self-aggregation is key to hair follicle (HF) induction ability of dermal papilla (DP) cells and neogenesis of HF can be achieved by transplanting DP microtissues. However, there is currently lack of a suitable system that allows efficient production of DP microtissues and analysis of DP self-aggregation in vitro. We demonstrate that, at a higher seeding cell density, poly(ethylene-co-vinyl alcohol) (EVAL) membranes facilitate DP self-assembly into many compact spheroidal microtissues that are able to induce new HFs. This self-assembling process is associated with an enhanced cell movement and a declined cell-substrate adhesivity on EVAL. A compromised cell growth is also revealed on EVAL. On the contrary, a more adherent surface allows faster cell expansion but maintains DP cells in a flat morphology. Dynamically, cell migration, intercellular collision and intercellular adhesion contribute to DP microtissue formation on EVAL. Our results suggest that, for large-scale production of DP microtissues for HF regeneration, an adhesive surface is needed for quick cell expansion and a biomaterial with a lower adhesivity is required for self-aggregation. In addition, this system can be a model for investigation of DP self-aggregation in vitro.

  18. Effects of transient receptor potential (TRP) channel agonists and antagonists on slowly adapting type II mechanoreceptors in the rat sinus hair follicle.

    PubMed

    Cahusac, Peter M B

    2009-12-01

    The possible functional role of transient receptor potential (TRP) channels was investigated by testing various TRP agonists and antagonists in an isolated rat sinus hair follicle preparation. Extracellular recordings from slowly adapting type II mechanoreceptor units were made. The antagonist capsazepine depressed spontaneous and mechanically evoked activity, with an IC(50) of 82 microM. In one-third of units, capsazepine caused a selective depression of mechanically evoked firing, such that the existing spontaneous firing was interrupted by an absence of activity during the mechanical stimulus. The broad spectrum TRP blocker ruthenium red (30 microM) had inconsistent effects, although in some units a delayed onset (following wash) bursting and paroxysmal firing ensued. The agonist icilin (50-100 microM) had an excitatory effect on spontaneous firing, and (-)-menthol (200 microM) had inconsistent effects. Cinnamaldehyde (1-2 mM) depressed all types of activity equally, mechanically evoked and spontaneous. Camphor (0.5-2 mM) also depressed all types of activity, although it had a preferential effect on spontaneous activity. Capsaicin (1-10 microM) and allyl isothiocyanate (50-100 microM) had no clear effects. These results rule out any role for TRPA1 and TRPV1 channels in mechanotransduction processes of slowly adapting type II mechanoreceptors.

  19. Androgens modify Wnt agonists/antagonists expression balance in dermal papilla cells preventing hair follicle stem cell differentiation in androgenetic alopecia.

    PubMed

    Leirós, Gustavo José; Ceruti, Julieta María; Castellanos, María Lía; Kusinsky, Ana Gabriela; Balañá, María Eugenia

    2017-01-05

    In androgenetic alopecia, androgens impair dermal papilla-induced hair follicle stem cell (HFSC) differentiation inhibiting Wnt signaling. Wnt agonists/antagonists balance was analyzed after dihydrotestosterone (DHT) stimulation in androgen-sensitive dermal papilla cells (DPC) cultured as spheroids or monolayer. In both culture conditions, DHT stimulation downregulated Wnt5a and Wnt10b mRNA while the Wnt antagonist Dkk-1 was upregulated. Notably, tissue architecture of DPC-spheroids lowers Dkk-1 and enhances Wnt agonists' basal expression; probably contributing to DPC inductivity. The role of Wnt agonists/antagonists as mediators of androgen inhibition of DPC-induced HFSC differentiation was evaluated. Inductive DPC-conditioned medium supplemented with DKK-1 impaired HFSC differentiation mimicking androgens' action. This effect was associated with inactivation of Wnt/β-catenin pathway in differentiating HFSC by both DPC-conditioned media. Moreover, addition of WNT10b to DPC-medium conditioned with DHT, overcame androgen inhibition of HFSC differentiation. Our results identify DKK1 and WNT10b as paracrine factors which modulate the HFSC differentiation inhibition involved in androgen-driven balding.

  20. The role of biodegradable engineered random polycaprolactone nanofiber scaffolds seeded with nestin-positive hair follicle stem cells for tissue engineering

    PubMed Central

    Yari, Abazar; Teimourian, Shahram; Amidi, Fardin; Bakhtiyari, Mehrdad; Heidari, Fatemeh; Sajedi, Nayereh; Veijouye, Sanaz Joulai; Dodel, Masumeh; Nobakht, Maliheh

    2016-01-01

    Background: Tissue engineering is a new approach to reconstruction and/or regeneration of lost or damaged tissue. The purpose of this study was to fabricate the polycaprolactone (PCL) random nanofiber scaffold as well as evaluation of the cell viability, adhesion, and proliferation of rat nestin-positive hair follicle stem cells (HFSCs) in the graft material using electrospun PCL nanofiber scaffold in regeneration medicine. Materials and Methods: The bulge HFSCs was isolated from rat whiskers and cultivated in Dulbecco's modified Eagle's medium/F12. To evaluate the biological nature of the bulge stem cells, flow cytometry using nestin, CD34 and K15 antibodies was performed. Electrospinning was used for the production of PCL nanofiber scaffolds. Furthermore, scanning electron microscopy (SEM) for HFSCs attachment, infiltration, and morphology, 3-(4, 5-di-methylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay for cell viability and cytotoxicity, tensile strength of the scaffolds mesh, and histology analysis were used. Results: Flow cytometry showed that HFSCs were nestin and CD34 positive but K15 negative. The results of the MTT assay showed cell viability and cell proliferation of the HFSCs on PCL nanofiber scaffolds. SEM microscopy photographs indicated that HFSCs are attached and spread on PCL nanofiber scaffolds. Furthermore, tensile strength of the scaffolds mesh was measured. Conclusion: The results of this study revealed that modified PCL nanofiber scaffolds are suitable for HFSCs seeding, attachment, and proliferation. Furthermore, HFSCs are attached and proliferated on PCL nanofiber scaffolds. PMID:26962524

  1. Blockade of Androgen Markers Using a Novel Betasitosterol, Thioctic Acid and Carnitine-containing Compound in Prostate and Hair Follicle Cell-based Assays.

    PubMed

    Chen, Li; Wang, Jiaolong; Mouser, Glen; Li, Yan Chun; Marcovici, Geno

    2016-06-01

    Androgenetic alopecia (AGA) affects approximately 70% of men and 40% of women in an age-dependent manner and is partially mediated by androgen hormones. Benign prostatic hyperplasia (BPH) similarly affects 50% of the male population, rising by 10% each decade. Finasteride inhibits 5-alpha reductase (5AR) and is used to treat both disorders, despite offering limited clinical benefits accompanied by significant adverse side effects. Building on our previous work demonstrating the efficacy of naturally derived 5AR inhibitors (such as stigmasterol and beta sitosterol), we hypothesize that targeting 5AR as well as inflammatory pathways may yield improved efficacy in AGA and BPH. Here we address these dual pathomechanisms by examining the potency of a novel composition using in vitro assays of representative cell lines for AGA (hair follicle dermal papilla cells) and BPH (LNCaP prostate cells), respectively. Exposure of cells to the novel test composition down-regulated mRNA expression profiles characteristic of both disease processes, which outperformed finasteride. Changes in mRNA expression were corroborated at the protein level as assessed by western blotting. These studies provide proof of concept that novel, naturally derived compositions simultaneously targeting 5AR and inflammatory mediators may represent a rational approach to treating AGA and BPH. Copyright © 2016 John Wiley & Sons, Ltd.

  2. Molecular genetic and endocrine mechanisms of hair growth.

    PubMed

    Alonso, Laura C; Rosenfield, Robert L

    2003-01-01

    The prenatal morphogenesis of hair follicles depends upon a precisely regulated series of molecular genetic processes. Hormones and their receptors play prominent roles in modulating postnatal hair cycling, which recapitulates some aspects of morphogenesis. The responses to androgen are the most obvious of these. The postnatal androgen sensitivity of pilosebaceous units in different skin areas is programmed during prenatal development to permit clinical outcomes such as hirsutism and pattern baldness. Thyroid hormone, glucocorticoids, insulin-like growth factor-I, and prolactin have clinically significant effects on specific aspects of hair growth. The nuclear receptors vitamin D receptor and retinoid X receptor are essential for postnatal hair cycling. Other hormones have less clear effects on hair growth. Advances in research on the interaction of hormone target genes with the biological processes involved in hair morphogenesis and cycling can be expected to improve management of hirsutism and alopecia.

  3. Radiobiology of the skin: review of some effects on epidermis and hair

    SciTech Connect

    Malkinson, F.D.; Keane, J.T.

    1981-07-01

    Significant doses of ionizing radiation produce an acute skin reaction characterized by erythema, epilation, and dry or moist desquamation with or without erosions. These early acute changes are dose-dependent and reflect damage to the germinative cells of the epidermis and to the cutaneous vasculature. Studies in the pig, for example, have shown that the degenerative phase of cell loss (2-3 weeks) results from reproductive failure in germinative cells and a sharp reduction in the proliferation rate of basal cell ''survivors.'' D0 values for epidermal cells in different species generally range from 100-140 rads. Cell maturation and ascension rates in the suprabasilar layers are largely unaffected. A regenerative phase of cell replacement, characterized by sharply increased cell replication rates, occurs from the 3rd to 5th postradiation weeks. The postregenerative phase of hyperplasia reflects a temporary overshoot of cell density above control levels; a subsequent decrease in hyperplasia indicates feedback control of cellular proliferation. Postradiation changes in the highly proliferative anagen hair matrix cell populations result in hair dysplasia, slowed growth rates, impaired metabolic processes, and alopecia. Dosages of 700-800 rads or more induce some degree of permanent hair loss. G0 telogen matrix cells are 2-3 times more radioresistant than proliferating anagen matrix cells, but may ''store'' radiation damage for prolonged periods. Altered matrix cell uptake of amino acids, the incidence of dysplasia, and the degree of alopecia occurring after irradiation have all been used as quantitative biological end-points for the general study of cellular radiation effects, as well as studies on the enhancement of or protection against radiation damage provided by certain pharmacologic or physical agents.

  4. Topical application of a protein kinase C inhibitor reduces skin and hair pigmentation.

    PubMed

    Park, Hee-Young; Lee, Jin; González, Salvador; Middelkamp-Hup, Maritza A; Kapasi, Sameer; Peterson, Shaun; Gilchrest, Barbara A

    2004-01-01

    To determine whether inhibition of PKC-beta activity decreases pigmentation, paired cultures of primary human melanocytes were first pretreated with bisindolylmaleimide (Bis), a selective PKC inhibitor, or vehicle alone for 30 min, and then treated with TPA for an additional 90 min to activate PKC in the presence of Bis. Bis blocked the expected induction of tyrosinase activity by activation of PKC. Addition of a peptide corresponding to amino acids 501-511 of tyrosinase containing its PKC-beta phosphorylation site, a presumptive PKC-beta pseudosubstrate, gave similar results. To determine whether Bis reduces pigmentation in vivo, the backs of four shaved and depilated pigmented guinea pigs were UV irradiated with a solar simulator for 2 wk excluding weekends. Compared to vehicle alone, Bis (300 microM), applied twice daily to paired sites for various periods encompassing the irradiation period, decreased tanning. Bis also, although less strikingly, reduced basal epidermal melanin when topically applied twice daily, 5 d per wk, for 3 wk to shaved and depilated unirradiated skin. Moreover, topical application of Bis (100 microM) once daily for 9 d to the freshly depilated backs of 8-wk-old mice markedly lightened the color of regrowing hair. These results demonstrate that inhibiting PKC activity in vivo selectively blocks tanning and reduces basal pigmentation in the epidermis and in anagen hair shafts.

  5. LGR5 expressing cells of hair follicle as potential targets for antibody mediated anti-cancer laser therapy

    NASA Astrophysics Data System (ADS)

    Popov, Boris V.

    2013-02-01

    Near infrared laser immunotherapy becomes now a new promising research field to cure the patients with cancers. One of the critical limitation in medical application of this treatment is availability of the specific markers for delivery of laser-sensitive nanoparticles. When coupled to antibodies to the cancer stem cells markers these nanoparticles may be delivered to the cancer tissue and mediate the laser induced thermolysis of the cancer stem cells that initiate and drive growth of cancer. This paper addresses the Lgr5 cell surface marker mediating the Wnt/β-catenin signal transduction as a potential target for anti-cancer laser immunotherapy of skin cancers.

  6. Body Hair

    MedlinePlus

    ... stop hair growth. The laser light can cause pain sometimes, but creams are used to numb the skin. If you use a lot of these creams, they can cause serious health problems, so talk to your doctor before having laser hair removal. Avoid sunlight when your skin is healing after laser removal. ...

  7. Beam shaping for cosmetic hair removal

    NASA Astrophysics Data System (ADS)

    Lizotte, Todd E.; Tuttle, Tracie

    2007-09-01

    Beam shaping has the potential to provide comfort to people who require or seek laser based cosmetic skin procedures. Of immediate interest is the procedure of aesthetic hair removal. Hair removal is performed using a variety of wavelengths from 480 to 1200 nm by means of filtered Xenon flash lamps (pulsed light) or 810 nm diode lasers. These wavelengths are considered the most efficient means available for hair removal applications, but current systems use simple reflector designs and plane filter windows to direct the light to the surface being exposed. Laser hair removal is achieved when these wavelengths at sufficient energy levels are applied to the epidermis. The laser energy is absorbed by the melanin (pigment) in the hair and hair follicle which in turn is transformed into heat. This heat creates the coagulation process, which causes the removal of the hair and prevents growth of new hair [1]. This paper outlines a technique of beam shaping that can be applied to a non-contact based hair removal system. Several features of the beam shaping technique including beam uniformity and heat dispersion across its operational treatment area will be analyzed. A beam shaper design and its fundamental testing will be discussed in detail.

  8. TGF-beta is specifically expressed in human dermal papilla cells and modulates hair folliculogenesis.

    PubMed

    Inoue, Keita; Aoi, Noriyuki; Yamauchi, Yuji; Sato, Takahiro; Suga, Hirotaka; Eto, Hitomi; Kato, Harunosuke; Tabata, Yasuhiko; Yoshimura, Kotaro

    2009-01-01

    Dermal papilla cells (DPCs) in the mammalian hair follicle have been shown to develop hair follicles through epithelial-mesenchymal interactions. A cell therapy to regenerate human hair is theoretically possible by expanding autologous human DPCs (hDPCs) and transplanting them into bald skin, though much remains to be overcome before clinical success. In this study, we compared gene signatures of hDPCs at different passages and human dermal fibroblasts, and found transforming growth factor (TGF)-beta(2) to be highly expressed in cultured hDPCs. Keratinocyte conditioned medium, which is known to help preserve the hair-inducing capacity of hDPCs, up-regulated TGF-beta(2) expression of hDPCs and also enhanced their alkaline phosphatase (ALP) activity, a known index for hair-inductive capacity. Through screening of components secreted from keratinocytes, the vitamin D(3) analogue was found to promote TGF-beta(2) expression and ALP activity of hDPCs. In animal hair folliculogenesis models using rat epidermis and expanded hDPCs, inhibition of TGF-beta(2) signalling at the ligand or receptor level significantly impaired hair folliculogenesis and maturation. These results suggest an important role for TGF-beta(2) in hair follicle morphogenesis and provide insights into the establishment of future cell therapies for hair regrowth by transplanting expanded DPCs.

  9. Ultra-structural hair alterations in Friedreich's ataxia: A scanning electron microscopic investigation.

    PubMed

    Turkmenoglu, F Pinar; Kasirga, U Baran; Celik, H Hamdi

    2015-08-01

    Friedreich's ataxia (FRDA) is an autosomal recessive inherited disorder involving progressive damage to the central and peripheral nervous systems and cardiomyopathy. FRDA is caused by the silencing of the FXN gene and reduced levels of the encoded protein, frataxin. Frataxin is a mitochondrial protein that functions primarily in iron-sulfur cluster synthesis. Skin disorders including hair abnormalities have previously been reported in patients with mitochondrial disorders. However, to our knowledge, ultra-structural hair alterations in FRDA were not demonstrated. The purpose of this study was to determine ultra-structural alterations in the hairs of FRDA patients as well as carriers. Hair specimen from four patients, who are in different stages of the disease, and two carriers were examined by scanning electron microscope. Thin and weak hair follicles with absence of homogeneities on the cuticular surface, local damages of the cuticular layer, cuticular fractures were detected in both carriers and patients, but these alterations were much more prominent in the hair follicles of patients. In addition, erosions on the surface of the cuticle and local deep cavities just under the cuticular level were observed only in patients. Indistinct cuticular pattern, pores on the cuticular surface, and presence of concavities on the hair follicle were also detected in patients in later stages of the disease. According to our results, progression of the disease increased the alterations on hair structure. We suggest that ultra-structural alterations observed in hair samples might be due to oxidative stress caused by deficient frataxin expression in mitochondria.

  10. Sterol Intermediates of Cholesterol Biosynthesis Inhibit Hair Growth and Trigger an Innate Immune Response in Cicatricial Alopecia

    PubMed Central

    Panicker, Sreejith P.; Ganguly, Taneeta; Consolo, Mary; Price, Vera; Mirmirani, Paradi; Honda, Kord; Karnik, Pratima

    2012-01-01

    Primary cicatricial alopecia (PCA) is a group of inflammatory hair disorders that cause scarring and permanent hair loss. Previous studies have implicated PPARγ, a transcription factor that integrates lipogenic and inflammatory signals, in the pathogenesis of PCA. However, it is unknown what triggers the inflammatory response in these disorders, whether the inflammation is a primary or secondary event in disease pathogenesis, and whether the inflammatory reaction reflects an autoimmune process. In this paper, we show that the cholesterol biosynthetic pathway is impaired in the skin and hair follicles of PCA patients. Treatment of hair follicle cells with BM15766, a cholesterol biosynthesis inhibitor, or 7-dehydrocholesterol (7-DHC), a sterol precursor, stimulates the expression of pro-inflammatory chemokine genes. Painting of mouse skin with 7-DHC or BM15766 inhibits hair growth, causes follicular plugging and induces the infiltration of inflammatory cells into the interfollicular dermis. Our results demonstrate that cholesterologenic changes within hair follicle cells trigger an innate immune response that is associated with the induction of toll-like receptor (TLR) and interferon (IFN) gene expression, and the recruitment of macrophages that surround the hair follicles and initiate their destruction. These findings reveal a previously unsuspected role for cholesterol precursors in PCA pathogenesis and identify a novel link between sterols and inflammation that may prove transformative in the diagnosis and treatment of these disorders. PMID:22685570

  11. Sterol intermediates of cholesterol biosynthesis inhibit hair growth and trigger an innate immune response in cicatricial alopecia.

    PubMed

    Panicker, Sreejith P; Ganguly, Taneeta; Consolo, Mary; Price, Vera; Mirmirani, Paradi; Honda, Kord; Karnik, Pratima

    2012-01-01

    Primary cicatricial alopecia (PCA) is a group of inflammatory hair disorders that cause scarring and permanent hair loss. Previous studies have implicated PPARγ, a transcription factor that integrates lipogenic and inflammatory signals, in the pathogenesis of PCA. However, it is unknown what triggers the inflammatory response in these disorders, whether the inflammation is a primary or secondary event in disease pathogenesis, and whether the inflammatory reaction reflects an autoimmune process. In this paper, we show that the cholesterol biosynthetic pathway is impaired in the skin and hair follicles of PCA patients. Treatment of hair follicle cells with BM15766, a cholesterol biosynthesis inhibitor, or 7-dehydrocholesterol (7-DHC), a sterol precursor, stimulates the expression of pro-inflammatory chemokine genes. Painting of mouse skin with 7-DHC or BM15766 inhibits hair growth, causes follicular plugging and induces the infiltration of inflammatory cells into the interfollicular dermis. Our results demonstrate that cholesterologenic changes within hair follicle cells trigger an innate immune response that is associated with the induction of toll-like receptor (TLR) and interferon (IFN) gene expression, and the recruitment of macrophages that surround the hair follicles and initiate their destruction. These findings reveal a previously unsuspected role for cholesterol precursors in PCA pathogenesis and identify a novel link between sterols and inflammation that may prove transformative in the diagnosis and treatment of these disorders.

  12. sPLA2 -IIA Overexpression in Mice Epidermis Depletes Hair Follicle Stem Cells and Induces Differentiation Mediated Through Enhanced JNK/c-Jun Activation.

    PubMed

    Sarate, Rahul M; Chovatiya, Gopal L; Ravi, Vagisha; Khade, Bharat; Gupta, Sanjay; Waghmare, Sanjeev K

    2016-09-01

    Secretory phospholipase A2 Group-IIA (sPLA2 -IIA) catalyzes the hydrolysis of the sn-2 position of glycerophospholipids to yield fatty acids and lysophospholipids. sPLA2 -IIA is deregulated in various cancers; however, its role in hair follicle stem cell (HFSC) regulation is obscure. Here we report a transgenic mice overexpressing sPLA2 -IIA (K14-sPLA2 -IIA) showed depletion of HFSC pool. This was accompanied with increased differentiation, loss of ortho-parakeratotic organization and enlargement of sebaceous gland, infundibulum and junctional zone. The colony forming efficiency of keratinocytes was significantly reduced. Microarray profiling of HFSCs revealed enhanced level of epithelial mitogens and transcription factors, c-Jun and FosB that may be involved in proliferation and differentiation. Moreover, K14-sPLA2 -IIA keratinocytes showed enhanced activation of EGFR and JNK1/2 that led to c-Jun activation, which co-related with enhanced differentiation. Further, depletion of stem cells in bulge is associated with high levels of chromatin silencing mark, H3K27me3 and low levels of an activator mark, H3K9ac suggestive of alteration in gene expression contributing toward stem cells differentiation. Our results, first time uncovered that overexpression of sPLA2 -IIA lead to depletion of HFSCs and differentiation associated with altered histone modification. Thus involvement of sPLA2 -IIA in stem cells regulation and disease pathogenesis suggest its prospective clinical implications. Stem Cells 2016;34:2407-2417.

  13. Dermoscopy for the pediatric dermatologist part I: dermoscopy of pediatric infectious and inflammatory skin lesions and hair disorders.

    PubMed

    Haliasos, Elena C; Kerner, Miryam; Jaimes-Lopez, Natalia; Rudnicka, Lidia; Zalaudek, Iris; Malvehy, Josep; Hofmann-Wellenhof, Rainer; Braun, Ralph P; Marghoob, Ashfaq A

    2013-01-01

    The dermoscope allows physicians to examine the macroscopic and microscopic primary morphology of skin lesions, identify subtle clinical clues, confirm naked-eye clinical diagnoses, and monitor treatment progress while posing little threat to the young patient. This review summarizes important dermoscopic structures seen in infectious and inflammatory skin conditions and hair disorders in children. Scabies, pediculosis, phthiriasis, molluscum contagiosum, tinea nigra, and verrucae are well characterized dermoscopically by delta-shaped structures, ovoid-shaped nits, the crab louse, red corona, brown strands or spicules, and multiple densely packed papilla with a central black dot surrounded by a whitish halo, respectively. These dermoscopic structures will be discussed, focusing on the dermoscopic morphologies and dermoscopic sensitivity for diagnosis and its utility in monitoring treatment progress. Dermoscopy has also been shown to significantly improve the clinician's diagnostic and monitoring accuracy of inflammatory skin lesions such as psoriasis, which is characterized dermoscopically by uniformly distributed dotted blood vessels, and lichen planus, which is characterized by whitish lines on a purple to reddish background. Dermoscopy of the hair and scalp (trichoscopy) facilitates the differential diagnosis of hair diseases in children, including alopecia areata, trichotillomania, and tinea capitis. It can also assist in the diagnosis of multiple genetic hair shaft disorders, such as monilethrix, trichorrhexis invaginata, trichorrhexis nodosa, pili torti, and pili annulati.

  14. The preventive effect of vitamin D3 on radiation-induced hair toxicity in a rat model.

    PubMed

    Baltalarli, Bahar; Bir, Ferda; Demirkan, Neşe; Abban, Gülçin

    2006-02-28

    Our aim is to investigate the protective effect of vitamin D3 especially from radiation-induced hair toxicity. A model of skin radiation injury was developed and a single fraction of 20 Gy Gamma irradiation was applied to the right dorsal skin of fourteen rats. All animals were randomly divided into 2 groups: Group I: irradiation alone (n = 7) and Group II: irradiation and 0.2 microg vitamin D3 given IM (n = 7). Fifty days after post-irradiation rats were sacrificed. The outcomes were evaluated on the basis of histopathological findings and immunohistochemical staining for Vitamin D receptor (VDR) in skin and hair follicles. The number of hair follicles in the radiation field for the group of animals irradiated without pretreatment was significantly lower than outside of the irradiated area (p = 0.016) as it is expected. Contrarily the number of hair follicles did not show significant difference in the pretreated group between the irradiated field and outside of the fields (p = 0,14). Skin of the vitamin D3 pretreated group demonstrated stronger immunoreactivity for VDR compared to irradiation alone group. These results indicate that administration of vitamin D3 may protect hair follicles from radiation toxicity. Further clinical trials should be conducted to prove the preventive effect of vitamin D3 as well as dosing and timing of the agent on radiation-induced alopecia.

  15. The additive effects of minoxidil and retinol on human hair growth in vitro.

    PubMed

    Yoo, Hyeon Gyeong; Chang, In-Young; Pyo, Hyun Keol; Kang, Yong Jung; Lee, Seung Ho; Kwon, Oh Sang; Cho, Kwang Hyun; Eun, Hee Chul; Kim, Kyu Han

    2007-01-01

    Minoxidil enhances hair growth by prolonging the anagen phase and induces new hair growth in androgenetic alopecia (AGA), whereas retinol significantly improves scalp skin condition and promotes hair growth. We investigated the combined effects of minoxidil and retinol on human hair growth in vitro and on cultured human dermal papilla cells (DPCs) and epidermal keratinocytes (HaCaT). The combination of minoxidil and retinol additively promoted hair growth in hair follicle organ cultures. In addition, minoxidil plus retinol more effectively elevated phosphorylated Erk, phosphorylated Akt levels, and the Bcl-2/Bax ratio than minoxidil alone in DPCs and HaCaT. We found that the significant hair shaft elongation demonstrated after minoxidil plus retinol treatment would depend on the dual kinetics associated with the activations of Erk- and Akt-dependent pathways and the prevention of apoptosis by increasing the Bcl-2/Bax ratio.

  16. Genetically induced cell death in bulge stem cells reveals their redundancy for hair and epidermal regeneration.

    PubMed

    Driskell, Iwona; Oeztuerk-Winder, Feride; Humphreys, Peter; Frye, Michaela

    2015-03-01

    Adult mammalian epidermis contains multiple stem cell populations in which quiescent and more proliferative stem and progenitor populations coexist. However, the precise interrelation of these populations in homeostasis remains unclear. Here, we blocked the contribution of quiescent keratin 19 (K19)-expressing bulge stem cells to hair follicle formation through genetic ablation of the essential histone methyltransferase Setd8 that is required for the maintenance of adult skin. Deletion of Setd8 eliminated the contribution of bulge cells to hair follicle regeneration through inhibition of cell division and induction of cell death, but the growth and morphology of hair follicles were unaffected. Furthermore, ablation of Setd8 in the hair follicle bulge blocked the contribution of K19-postive stem cells to wounded epidermis, but the wound healing process was unaltered. Our data indicate that quiescent bulge stem cells are dispensable for hair follicle regeneration and epidermal injury in the short term and support the hypothesis that quiescent and cycling stem cell populations are equipotent.

  17. Mechanistic study of decreased skin penetration using a combination of sonophoresis with sodium fluorescein-loaded PEGylated liposomes with d-limonene

    PubMed Central

    Rangsimawong, Worranan; Opanasopit, Praneet; Rojanarata, Theerasak; Ngawhirunpat, Tanasait

    2015-01-01

    The effect of low frequency sonophoresis (SN, 20 kHz) on the skin transport of sodium fluorescein (NaFI)-loaded liposomes was investigated. An in vitro skin penetration study in open and blocked hair follicles was performed, and confocal laser scanning microscopy and scanning electron microscopy were used to visualize the penetration pathways. The results showed that SN significantly increased the flux of NaFI solution, whereas it significantly decreased the flux of NaFI-loaded polyethylene glycol-coated (PEGylated) liposomes with D-limonene (PL-LI). SN did not significantly affect the flux of NaFI-loaded conventional liposomes and PEGylated liposomes. In the blocked follicles, the flux of NaFI-loaded PL-LI both with and without SN decreased, indicating that NaFI-loaded PL-LI penetrated the skin via the transfollicular pathway. A confocal laser scanning microscopy image showed that in the skin without SN, the fluorescence intensity of NaFI-loaded PL-LI was observed in the skin and along the length of hair inside the skin, whereas in the skin with applied SN, the fluorescence intensity was detected only on the top of hair outside the skin. From scanning electron microscopy images, SN dislocated the corneocytes and reduced the deposition of PL-LI around hair follicles. These results revealed that SN may partially plug hair follicle orifices and reduce percutaneous absorption through the follicular pathway. PMID:26719685

  18. Mechanistic study of decreased skin penetration using a combination of sonophoresis with sodium fluorescein-loaded PEGylated liposomes with d-limonene.

    PubMed

    Rangsimawong, Worranan; Opanasopit, Praneet; Rojanarata, Theerasak; Ngawhirunpat, Tanasait

    2015-01-01

    The effect of low frequency sonophoresis (SN, 20 kHz) on the skin transport of sodium fluorescein (NaFI)-loaded liposomes was investigated. An in vitro skin penetration study in open and blocked hair follicles was performed, and confocal laser scanning microscopy and scanning electron microscopy were used to visualize the penetration pathways. The results showed that SN significantly increased the flux of NaFI solution, whereas it significantly decreased the flux of NaFI-loaded polyethylene glycol-coated (PEGylated) liposomes with D-limonene (PL-LI). SN did not significantly affect the flux of NaFI-loaded conventional liposomes and PEGylated liposomes. In the blocked follicles, the flux of NaFI-loaded PL-LI both with and without SN decreased, indicating that NaFI-loaded PL-LI penetrated the skin via the transfollicular pathway. A confocal laser scanning microscopy image showed that in the skin without SN, the fluorescence intensity of NaFI-loaded PL-LI was observed in the skin and along the length of hair inside the skin, whereas in the skin with applied SN, the fluorescence intensity was detected only on the top of hair outside the skin. From scanning electron microscopy images, SN dislocated the corneocytes and reduced the deposition of PL-LI around hair follicles. These results revealed that SN may partially plug hair follicle orifices and reduce percutaneous absorption through the follicular pathway.

  19. Production of transgenic cashmere goat embryos expressing red fluorescent protein and containing IGF1 hair-follicle-cell specific expression cassette by somatic cell nuclear transfer.

    PubMed

    Guo, XuDong; Yang, DongShan; Ao, XuDong; Wu, Xia; Li, GuangPeng; Wang, LingLing; Bao, Ming-Tao; Xue, Lian; Bou, ShorGan

    2009-04-01

    In the present study, cashmere goat fetal fibroblasts were transfected with pCDsR-KI, a hair-follicle-cell specific expression vector for insulin-like growth factor 1 (IGF1) that contains two markers for selection (red fluorescent protein gene and neomycin resistant gene). The transgenic fibroblasts cell lines were obtained after G418 selection. Prior to the somatic cell nuclear transfer (SCNT), the maturation rate of caprine cumulus oocytes complexes (COCs) was optimized to an in vitro maturation time of 18 h. Parthenogenetic ooctyes were used as a model to investigate the effect of two activation methods, one with calcium ionophore IA23187 plus 6-DMAP and the other with ethanol plus 6-DMAP. The cleavage rates after 48 h were respectively 88.7% and 86.4%, with no significant difference (P>0.05). There was no significant difference between the cleavage rate and the blastocyst rate in two different media (SO-Faa and CR1aa; 86.3% vs 83.9%, P>0.05 and 23.1% vs 17.2%, P>0.05). The fusion rate of a 190 V/mm group (62.4%) was significantly higher than 130 V/mm (32.8%) and 200 V/mm (42.9%), groups (P>0.05). After transgenic somatic cell nuclear transfer (TSCNT) manipulation, 203 reconstructed embryos were obtained in which the cleavage rate after in vitro development (IVD) for 48 h was 79.3% (161/203). The blastocyst rate after IVD for 7 to 9 d was 15.3% (31/203). There were 17 embryos out of 31 strongly expressing red fluorescence. Two of the red fluorescent blastocysts were randomly selected to identify transgene by polymerase chain reaction. Both were positive. These results showed that: (i) RFP and Neo ( r ) genes were correctly expressed indicating that transgenic somatic cell lines and positive transgenic embryos were obtained; (ii) one more selection at the blastocyst stage was necessary although the donor cells were transgenic positive, because only partially transgenic embryos expressing red fluorescence were obtained; and (iii) through TSCNT manipulation and

  20. miR-18b inhibits TGF-β1-induced differentiation of hair follicle stem cells into smooth muscle cells by targeting SMAD2.

    PubMed

    Liu, Xuejuan; Song, Lei; Liu, Jinyu; Wang, Shichao; Tan, Xiaohua; Bai, Xiaoguang; Bai, Tingting; Wang, Yimei; Li, Meiying; Song, Yaolin; Li, Yulin

    2013-08-30

    Human hair follicle mesenchymal stem cells (hHF-MSCs) are capable of differentiating into smooth muscle cells (SMCs) in response to transforming growth factor-β (TGF-β), and thus can be used for cardiovascular tissue engineering and regenerative medicine. However, the precise molecular mechanisms underlying SMC conversion of hHF-MSCs are still undefined. MicroRNAs (miRNAs) are small noncoding RNAs that modulate gene expression post-transcriptionally by binding to the complementary sequences of targeted mRNAs. Accumulating evidence indicates that miRNAs are associated with SMC differentiation in vitro andin vivo. In this study, we revealed that miR-18b was significantly downregulated during TGF-β1-induced hHF-MSCs differentiation into SMC using miRNA array profiling and quantitative RT- PCR (qRT-PCR). Over-expression of miR-18b in hHF-MSCs led to remarkable downregulation of SMC-specific markers such as SMA and calponin proteins. On the contrary, inhibition of endogenous miR-18b by its antisense oligonucleotide antagomir-18b reversed the changes of SMA and calponin proteins. We also showed that SMAD2, a key transcription regulator in TGF-β signaling which was involved in SMC differentiation, is regulated by miR-18b. miR-18b could suppress the expression of SMAD2 protein by targeting the 3'UTR of SMAD2 gene without affecting its mRNA level in hHF-MSCs. Moreover, knockdown of SMAD2 by RNA interference could block the effect of inhibition of miR-18b on SMC differentiation, indicating that SMAD2 contributed to miR-18b mediated regulation of TGF-β-induced SMC differentiation. In conclusion, this study demonstrated that miR-18b regulated the TGF-β1-induced differentiation of hHF-MSCs into SMCs by targeting SMAD2 gene, and provided novel insights into the regulatory mechanisms of TGF-β-induced SMC differentiation.

  1. Non-competitive metabotropic glutamate 1 receptor antagonists block activity of slowly adapting type I mechanoreceptor units in the rat sinus hair follicle.

    PubMed

    Cahusac, P M B; Mavulati, S C

    2009-10-20

    Previous studies suggested that Group I metabotropic glutamate (mGlu) receptors play a role in mechanotransduction processes of slowly adapting type I mechanoreceptors. Using an isolated rat sinus hair follicle preparation we tested a range of compounds. Surprisingly, only non-competitive mGlu1 receptor antagonists produced profound and long-lasting depression of mechanically evoked firing. 6-Amino-N-cyclohexyl-N,3-dimethylthiazolo[3,2-alpha]benzimidazole-2-carboxamide hydrochloride (YM-298198) had an IC(50) of 8.7 muM (95% CI 5.7 to 13.2 microM), representing the most potent known blocker of type I mechanoreceptors. The derivative 6-amino-N-cyclohexyl-3-methylthiazolo[3,2-alpha]benzimidazole-2-carboxamide hydrochloride (desmethyl YM-298198) had a comparable potency. Another compound 7-(hydroxyimino)cyclopropa[b]chromen-1a-carboxylate ethyl ester (CPCCOEt) had a similar depressant effect, although it was less potent with an approximate IC(50) of 100 microM. Between three and seven times the concentration of CPCCOEt and YM-298198 respectively was required to produce similar depressions in slowly adapting type II units. No depression, and some weak excitatory effects, were observed using the following ligands: the competitive mGlu1 receptor antagonist alpha-amino-5-carboxy-3-methyl-2-thiopheneacetic acid (3-MATIDA) (300 microM), the phosphoserine phosphatase inhibitor dl-2-amino-3-phosphonopropionic acid (dl-AP3) (2 mM), non-competitive mGlu5 receptor antagonists 3-((2-methyl-1,3-thiazol-4-yl)ethynyl)pyridine; (S)-3,5-DHPG, (S)-3,5-dihydroxyphenylglycine (MTEP) (10 microM) and 2-methyl-6-(phenylethynyl)pyridine hydrochloride (MPEP) (100 microM), the mGlu1 receptor agonist (S)-3,5-dihydroxyphenylglycine ((S)-3,5-DHPG) (500 microM), and the mGlu5 receptor agonist (RS)-2-chloro-5-hydroxyphenylglycine (CHPG) (1 mM). The results suggest that the non-competitive mGlu1 receptor antagonists are not acting at conventional mGlu1 receptors but at other binding sites, possibly

  2. Insulin-like growth factor 1 and hair growth.

    PubMed

    Su, H Y; Hickford, J G; Bickerstaffe, R; Palmer, B R

    1999-11-01

    Insulin-like growth factor 1 (IGF-1) has been identified as an important growth factor in many biological systems.[1] It shares considerable structural homology with insulin and exerts insulin-like effects on food intake and glucose metabolism. Recently it has been suggested to play a role in regulating cellular proliferation and migration during the development of hair follicles. [2,3] To exert its biological effects, the IGF-1 is required to activate cells by binding to specific cell-surface receptors. The type I IGF receptor (IGF-1R) is the only IGF receptor to have IGF-mediated signaling functions.[1] In circulation, this growth factor mediates endocrine action of growth hormone (GH) on somatic growth and is bound to specific binding proteins (BPs). The latter control IGF transport, efflux from vascular compartments and association with cell surface receptors.[4] In tissues, IGF-1 is produced by mesenchymal type cells and acts in a paracrine and autocrine fashion by binding to the IGF-1R. This binding activates the receptor tyrosine kinase (RTK) that triggers the downstream responses and finally stimulates cell division.[5] IGF-1 may therefore be able to stimulate the proliferation of hair follicle cells through cellular signaling pathways of its receptors. Local infusion of IGF-1 into sheep has been reported to be capable of stimulating protein synthesis in the skin.[6] It may also increase the production of wool keratin. Recently, transgenic mice overexpressing IGF-1 in the skin have been shown to have earlier hair follicle development than controls.[7] In addition, this growth factor plays an important role in many cell types as a survival factor to prevent cell death.[8] This anti-apoptotic function of IGF-1 may be important to the development of follicle cells as follicles undergo a growth cycle where the regressive, catagen phase is apoptosis driven. In this review, the effects of IGF-1 on follicle cell proliferation and differentiation are discussed. In

  3. Scurvy, corkscrew hair (image)

    MedlinePlus

    Scurvy is a nutritional disease caused by deficiency of vitamin C. Pinpoint bleeding around hair follicles, and " ... this picture, can occur as a result of scurvy. Bleeding along the gums is common. This disease ...

  4. An ultraviolet-radiation-independent pathway to melanoma carcinogenesis in the red hair/fair skin background.

    PubMed

    Mitra, Devarati; Luo, Xi; Morgan, Ann; Wang, Jin; Hoang, Mai P; Lo, Jennifer; Guerrero, Candace R; Lennerz, Jochen K; Mihm, Martin C; Wargo, Jennifer A; Robinson, Kathleen C; Devi, Suprabha P; Vanover, Jillian C; D'Orazio, John A; McMahon, Martin; Bosenberg, Marcus W; Haigis, Kevin M; Haber, Daniel A; Wang, Yinsheng; Fisher, David E

    2012-11-15

    People with pale skin, red hair, freckles and an inability to tan--the 'red hair/fair skin' phenotype--are at highest risk of developing melanoma, compared to all other pigmentation types. Genetically, this phenotype is frequently the product of inactivating polymorphisms in the melanocortin 1 receptor (MC1R) gene. MC1R encodes a cyclic AMP-stimulating G-protein-coupled receptor that controls pigment production. Minimal receptor activity, as in red hair/fair skin polymorphisms, produces the red/yellow pheomelanin pigment, whereas increasing MC1R activity stimulates the production of black/brown eumelanin. Pheomelanin has weak shielding capacity against ultraviolet radiation relative to eumelanin, and has been shown to amplify ultraviolet-A-induced reactive oxygen species. Several observations, however, complicate the assumption that melanoma risk is completely ultraviolet-radiation-dependent. For example, unlike non-melanoma skin cancers, melanoma is not restricted to sun-exposed skin and ultraviolet radiation signature mutations are infrequently oncogenic drivers. Although linkage of melanoma risk to ultraviolet radiation exposure is beyond doubt, ultraviolet-radiation-independent events are likely to have a significant role. Here we introduce a conditional, melanocyte-targeted allele of the most common melanoma oncoprotein, BRAF(V600E), into mice carrying an inactivating mutation in the Mc1r gene (these mice have a phenotype analogous to red hair/fair skin humans). We observed a high incidence of invasive melanomas without providing additional gene aberrations or ultraviolet radiation exposure. To investigate the mechanism of ultraviolet-radiation-independent carcinogenesis, we introduced an albino allele, which ablates all pigment production on the Mc1r(e/e) background. Selective absence of pheomelanin synthesis was protective against melanoma development. In addition, normal Mc1r(e/e) mouse skin was found to have significantly greater oxidative DNA and lipid

  5. Cornu cervi pantotrichum Pharmacopuncture Solution Facilitate Hair Growth in C57BL/6 Mice

    PubMed Central

    Lee, Seon-Yong; Lee, Dong-Jin; Kwon, Kang; Lee, Chang-Hyun; Shin, Hyun Jong; Kim, Jai Eun; Ha, Ki-Tae; Jeong, Han-Sol

    2016-01-01

    Objectives: Cornu cervi pantotrichum (CCP) has been widely used in Korean and China, as an anti-fatigue, anti-aging, and tonic agent to enhance the functions of the reproductive and the immune systems. Because CCP has various growth factors that play important roles in the development of hair follicles, we examined whether CCP pharmacopuncture solution (CCPPS) was capable of promoting hair growth in an animal model. Methods: One day after hair depilation, CCPPS were topically applied to the dorsal skin of C57BL/6 mice once a day for 15 days. Hair growth activity was evaluated by using macro- and microscopic observations. Dorsal skin tissues were stained with hematoxylin and eosin. Expressions of bromodeoxyuridine (BrdU), proliferating cell nuclear antigen (PCNA), and fibroblast growth factor (FGF)-7 were examined by using immunohistochemical staining. A reverse transcription polymerase chain reaction (RT-PCR) analysis was also conducted to measure the messenger RNA (mRNA) expression of FGF-7. Results: CCPPS induced more active hair growth than normal saline. Histologic analysis showed enlargement of the dermal papilla, elongation of the hair shaft, and expansion of hair thickness in CCPPS treated mice, indicating that CCPPS effectively induced the development of anagen. CCPPS treatment markedly increased the expressions of BrdU and PCNA in the hair follicles of C57BL/6 mice. In addition, CCPPS up regulated the expression of FGF-7, which plays an important role in the development of hair follicles. Conclusion: These results reveal that CCPPS facilitates hair re-growth by proliferation of hair follicular cells and up-regulation of FGF-7 and suggest that CCPPS can potentially be applied as an alternative treatment for patients with alopecia. PMID:27386145

  6. Sensory innervation of the hairy skin (light- and electronmicroscopic study.

    PubMed

    Halata, Z

    1993-07-01

    The sense of touch develops early in phylogeny and is one of the most important senses for the survival of the animal. Touch organs of hairy skin in mammals include the so-called "Haarscheiben" (also Pinkus corpuscles) and all types of hair follicles with their nerve endings. The touch organs of the skin consist of a mechanical transducing component and the sensory component. The epithelium and its derivatives like hair follicles and sebaceous glands are the mechanical transducing component transmitting the mechanical forces like pressure or touch to the second component--the sensory nerve endings. In mammalian hairy skin all sinus and guard hairs and many vellus hairs are touch organs. The sinus hair is a typical example of a touch organ. All mammals except humans are equipped with these highly differentiated touch organs. The hair follicle is almost completely embedded in a blood sinus and equipped with more than 2,000 sensory nerve endings. All sinus and guard hairs are equipped with free nerve endings (nociceptors), Merkel nerve endings (slowly adapting [SA I] mechanoreceptor units-pressure detectors), palisades of lanceolate nerve endings (velocity detectors), and pilo-Ruffini corpuscles (tension receptors). In most of the sinus hairs lamellated corpuscles of Pacini type could be found (rapidly adapting receptors-acceleration detectors). Most vellus hairs are equipped with free and lanceolate nerve endings. Some of the vellus hairs of the upper portion of the body (head, upper extremity) are innervated by Merkel nerve endings. The presence of pilo-Ruffini nerve endings in vellus hairs is very unusual.

  7. Isoproterenol directs hair follicle-associated pluripotent (HAP) stem cells to differentiate in vitro to cardiac muscle cells which can be induced to form beating heart-muscle tissue sheets.

    PubMed

    Yamazaki, Aiko; Yashiro, Masateru; Mii, Sumiyuki; Aki, Ryoichi; Hamada, Yuko; Arakawa, Nobuko; Kawahara, Katsumasa; Hoffman, Robert M; Amoh, Yasuyuki

    2016-01-01

    Nestin-expressing hair-follicle-associated pluripotent (HAP) stem cells are located in the bulge area of the follicle. Previous studies have shown that HAP stem cells can differentiate to neurons, glia, keratinocytes, smooth muscle cells, and melanocytes in vitro. HAP stem cells effected nerve and spinal cord regeneration in mouse models. Recently, we demonstrated that HAP stem cells differentiated to beating cardiac muscle cells. The differentiation potential to cardiac muscle cells was greatest in the upper part of the follicle. The beat rate of the cardiac muscle cells was stimulated by isoproterenol. In the present study, we observed that isoproterenol directs HAP stem cells to differentiate to cardiac muscle cells in large numbers in culture compared to HAP stem cells not supplemented with isoproterenol. The addition of activin A, bone morphogenetic protein 4, and basic fibroblast growth factor, along with isoproternal, induced the cardiac muscle cells to form tissue sheets of beating heart muscle cells. These results demonstrate that HAP stem cells have great potential to form beating cardiac muscle cells in tissue sheets.

  8. Fibroblast heterogeneity: more than skin deep.

    PubMed

    Sorrell, J Michael; Caplan, Arnold I

    2004-02-15

    Dermal fibroblasts are a dynamic and diverse population of cells whose functions in skin in many respects remain unknown. Normal adult human skin contains at least three distinct subpopulations of fibroblasts, which occupy unique niches in the dermis. Fibroblasts from each of these niches exhibit distinctive differences when cultured separately. Specific differences in fibroblast physiology are evident in papillary dermal fibroblasts, which reside in the superficial dermis, and reticular fibroblasts, which reside in the deep dermis. Both of these subpopulations of fibroblasts differ from the fibroblasts that are associated with hair follicles. Fibroblasts engage in fibroblast-epidermal interactions during hair development and in interfollicular regions of skin. They also play an important role in cutaneous wound repair and an ever-increasing role in bioengineering of skin. Bioengineered skin currently performs important roles in providing (1) a basic understanding of skin biology, (2) a vehicle for testing topically applied products and (3) a resource for skin replacement.

  9. Hox in hair growth and development

    NASA Astrophysics Data System (ADS)

    Awgulewitsch, Alexander

    2003-05-01

    The evolutionarily conserved Hox gene family of transcriptional regulators has originally been known for specifying positional identities along the longitudinal body axis of bilateral metazoans, including mouse and man. It is believed that subsequent to this archaic role, subsets of Hox genes have been co-opted for patterning functions in phylogenetically more recent structures, such as limbs and epithelial appendages. Among these, the hair follicle is of particular interest, as it is the only organ undergoing cyclical phases of regression and regeneration during the entire life span of an organism. Furthermore, the hair follicle is increasingly capturing the attention of developmental geneticists, as this abundantly available miniature organ mimics key aspects of embryonic patterning and, in addition, presents a model for studying organ renewal. The first Hox gene shown to play a universal role in hair follicle development is Hoxc13, as both Hoxc13-deficient and overexpressing mice exhibit severe hair growth and patterning defects. Differential gene expression analyses in the skin of these mutants, as well as in vitro DNA binding studies performed with potential targets for HOXC13 transcriptional regulation in human hair, identified genes encoding hair-specific keratins and keratin-associated proteins (KAPs) as major groups of presumptive Hoxc13 downstream effectors in the control of hair growth. The Hoxc13 mutant might thus serve as a paradigm for studying hair-specific roles of Hoxc13 and other members of this gene family, whose distinct spatio-temporally restricted expression patterns during hair development and cycling suggest discrete functions in follicular patterning and hair cycle control. The main conclusion from a discussion of these potential roles vis-à-vis current expression data in mouse and man, and from the perspective of the results obtained with the Hoxc13 transgenic models, is that members of the Hox family are likely to fulfill essential roles

  10. A function for Rac1 in the terminal differentiation and pigmentation of hair.

    PubMed

    Behrendt, Kristina; Klatte, Jennifer; Pofahl, Ruth; Bloch, Wilhelm; Smyth, Neil; Tscharntke, Michael; Krieg, Thomas; Paus, Ralf; Niessen, Carien; Niemann, Catherin; Brakebusch, Cord; Haase, Ingo

    2012-02-15

    The small GTPase Rac1 is ubiquitously expressed in proliferating and differentiating layers of the epidermis and hair follicles. Previously, Rac1 was shown to regulate stem cell behaviour in these compartments. We have asked whether Rac1 has, in addition, a specific, stem-cell-independent function in the regulation of terminal hair follicle differentiation. To address this, we have expressed a constitutively active mutant of Rac1, L61Rac1, only in the basal epidermal layer and outer root sheath of mice possessing an epidermis-specific deletion of endogenous Rac1, which experience severe hair loss. The resulting 'rescue' mice exhibited a hair coat throughout their lives. Therefore, expression of Rac1 activity in the keratin-14-positive compartment of the skin is sufficient for the formation of hair follicles and hair in normal quantities. The quality of hair formed in rescue mice was, however, not normal. Rescue mice showed a grey, dull hair coat, whereas that of wild-type and L61Rac1-transgenic mice was black and shiny. Hair analysis in rescue mice revealed altered structures of the hair shaft and the cuticle and disturbed organization of medulla cells and pigment distribution. Disorganization of medulla cells correlates with the absence of cortical, keratin-filled spikes that normally protrude from the cortex into the medulla. The desmosomal cadherin Dsc2, which normally decorates these protrusions, was found to be reduced or absent in the hair of rescue mice. Our study demonstrates regulatory functions for Rac1 in the formation of hair structure and pigmentation and thereby identifies, for the first time, a role for Rac1 in terminal differentiation.

  11. Effect of ultraviolet radiation, smoking and nutrition on hair.

    PubMed

    Trüeb, Ralph M

    2015-01-01

    Similar to the rest of the skin, the hair is exposed to noxious environmental factors. While ultraviolet radiation (UVR) and smoking are well appreciated as major factors contributing to the extrinsic aging of the skin, their effects on the condition of hair have only lately attracted the attention of the medical community. Terrestrial solar UVR ranges from approximately 290 to 400 nm; UV-B (290-315 nm) reaches only the upper dermis, while the penetration of UV-A (315-400 nm) into the dermis increases with wavelength. The two most important chronic effects of UVR on the skin and bald scalp are photocarcinogenesis and solar elastosis; however, the effects of UVR on hair have largely been ignored. As a consequence of increased leisure time and a growing popularity of outdoor activities and holidays in the sun, the awareness of sun protection of the skin has become important and should also apply to the hair. Besides being the single-most preventable cause of significant cardiovascular and pulmonary morbidity and an important cause of death, the association of tobacco smoking with various adverse effects on the skin and hair has also been recognized. Increasing public awareness of the association between smoking and hair loss seems to offer a good opportunity for the prevention or cessation of smoking, since the appearance of hair plays an important role in the overall physical appearance and self-perception of people. Finally, the quantity and quality of hair are closely related to the nutritional state of an individual. Normal supply, uptake, and transport of proteins, calories, trace elements, and vitamins are of fundamental importance in tissues with high biosynthetic activity, such as the hair follicle. In instances of protein and calorie malnutrition as well as essential amino acid, trace element, and vitamin deficiencies, hair growth and pigmentation may be impaired. Ultimately, important commercial interest lies in the question of whether increasing the

  12. Histology and Ultrastructure of Transitional Changes in Skin Morphology in the Juvenile and Adult Four-Striped Mouse (Rhabdomys pumilio)

    PubMed Central

    Stewart, Eranée; Ajao, Moyosore Salihu

    2013-01-01

    The four-striped mouse has a grey to brown coloured coat with four characteristic dark stripes interspersed with three lighter stripes running along its back. The histological differences in the skin of the juvenile and adult mouse were investigated by Haematoxylin and Eosin and Masson Trichrome staining, while melanocytes in the skin were studied through melanin-specific Ferro-ferricyanide staining. The ultrastructure of the juvenile skin, hair follicles, and melanocytes was also explored. In both the juvenile and adult four-striped mouse, pigment-containing cells were observed in the dermis and were homogeneously dispersed throughout this layer. Apart from these cells, the histology of the skin of the adult four-striped mouse was similar to normal mammalian skin. In the juvenile four-striped mouse, abundant hair follicles of varying sizes were observed in the dermis and hypodermis, while hair follicles of similar size were only present in the dermis of adult four-striped mouse. Ultrastructural analysis of juvenile hair follicles revealed that the arrangement and differentiation of cellular layers were typical of a mammal. This study therefore provides unique transition pattern in the four-striped mouse skin morphology different from the textbook description of the normal mammalian skin. PMID:24288469

  13. Histology and ultrastructure of transitional changes in skin morphology in the juvenile and adult four-striped mouse (Rhabdomys pumilio).

    PubMed

    Stewart, Eranée; Ajao, Moyosore Salihu; Ihunwo, Amadi Ogonda

    2013-01-01

    The four-striped mouse has a grey to brown coloured coat with four characteristic dark stripes interspersed with three lighter stripes running along its back. The histological differences in the skin of the juvenile and adult mouse were investigated by Haematoxylin and Eosin and Masson Trichrome staining, while melanocytes in the skin were studied through melanin-specific Ferro-ferricyanide staining. The ultrastructure of the juvenile skin, hair follicles, and melanocytes was also explored. In both the juvenile and adult four-striped mouse, pigment-containing cells were observed in the dermis and were homogeneously dispersed throughout this layer. Apart from these cells, the histology of the skin of the adult four-striped mouse was similar to normal mammalian skin. In the juvenile four-striped mouse, abundant hair follicles of varying sizes were observed in the dermis and hypodermis, while hair follicles of similar size were only present in the dermis of adult four-striped mouse. Ultrastructural analysis of juvenile hair follicles revealed that the arrangement and differentiation of cellular layers were typical of a mammal. This study therefore provides unique transition pattern in the four-striped mouse skin morphology different from the textbook description of the normal mammalian skin.

  14. Regenerative hair waves in aging mice and extra-follicular modulators Follistatin, Dkk1 and Sfrp4

    PubMed Central

    Chen, Chih-Chiang; Murray, Philip J.; Jiang, Ting Xin; Plikus, Maksim V; Chang, Yun-Ting; Lee, Oscar K.; Widelitz, Randall B.; Chuong, Cheng Ming

    2014-01-01

    Hair cycling is modulated by factors both intrinsic and extrinsic to hair follicles. Cycling defects lead to conditions such as aging associated alopecia. Recently we demonstrated that mouse skin exhibits regenerative hair waves, reflecting a coordinated regenerative behavior in follicle populations. Here, we use this model to explore the regenerative behavior of aging mouse skin. Old mice (>18 months) tracked over several months show that with progressing age hair waves slow down, wave propagation becomes restricted, and hair cycle domains fragment into smaller domains. Transplanting aged donor mouse skin to a young host can restore donor cycling within a 3mm range of the interface, suggesting that changes are due to extra-cellular factors. Therefore, hair stem cells in aged skin can be re-activated. Molecular studies show that extra-follicular modulators Bmp2, Dkk1, and Sfrp4 increase in early anagen. Further, we identify follistatin as an extra-follicular modulator which is highly expressed in late telogen and early anagen. Indeed follistatin induces hair wave propagation and its level decreases in aging mice. We present an excitable medium model to simulate the cycling behavior in aging mice and illustrate how the inter-organ macro-environment can regulate the aging process by integrating both “activator” and “inhibitor” signals. PMID:24618599

  15. Erythroid Differentiation Regulator 1 as a Novel Biomarker for Hair Loss Disorders

    PubMed Central

    Woo, Yu Ri; Hwang, Sewon; Jeong, Seo Won; Cho, Dae Ho; Park, Hyun Jeong

    2017-01-01

    Erythroid differentiation regulator 1 (Erdr1) is known to be involved in the inflammatory process via regulating the immune system in many cutaneous disorders, such as psoriasis and rosacea. However, the role of Erdr1 in various hair loss disorders remains unclear. The aim of this study was to investigate the putative role of Erdr1 in alopecias. Skin samples from 21 patient