Unraveling the secret life of the hair follicle: from fungi to innovative hair loss therapies

Dengue virus (DENV)-mediated hair loss is one of the post-dengue fatigue syndromes and its pathophysiology remains unknown. Whether long-term or persistent infection with DENV in the scalp results in hair loss is unclear. In this study, we cultured human dermal fibroblasts (WS1 cells) and primary human hair-follicle dermal papilla cells (HFDPCs) in the long term with DENV-2 infection. The production of virion, the expression of inflammatory and anti-virus genes, and their signaling transduction activity in the infected cells were analyzed. DENV-2 NS3 protein and DENV-2 5′ UTR RNA were detected in fibroblasts and HFDPCs that were subjected to long-term infection with DENV-2 for 33 days. A significant amount of DENV-2 virion was produced by both WS1 cells and HFDPCs in the first two days of acute infection. The virion was also detected in WS1 cells that were infected in the long term, but HFDPCs failed to produce DENV-2 after long-term culture. Type I and type III interferons, and inflammatory cytokines were highly expressed in the acute phase of DENV infection in HFPDC and WS1 cells. However, in the long-term cultured cells, modest levels of anti-viral protein genes were expressed and we observed reduced signaling activity, which was correlated with the level of virus production changes. Long-term infection of DENV-2 downregulated the expression of hair growth regulatory factors, such as Rip1, Wnt1, and Wnt4. This in vitro study shows that the long-term infection with DENV-2 in dermal fibroblasts and dermal papilla cells may be involved with the prolonged-DENV-infection-mediated hair loss of post-dengue fatigue syndrome. However, direct evidence for viral replication in the human hair of a dengue victim or animal infection model is required.

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Advances in Regenerative Stem Cell Therapy in Androgenic Alopecia and Hair Loss: Wnt Pathway, Growth-Factor, and Mesenchymal Stem Cell Signaling Impact Analysis on Cell Growth and Hair Follicle Development

Cells ◽

10.3390/cells8050466 ◽

2019 ◽

Vol 8 (5) ◽

pp. 466 ◽

Cited By ~ 46

Author(s):

Pietro Gentile ◽

Simone Garcovich

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Cell Growth ◽

Mesenchymal Stem Cell ◽

Hair Follicle ◽

Hair Loss ◽

Hair Growth ◽

Follicle Development ◽

Hair Regrowth ◽

Hair Follicle Development

The use of stem cells has been reported to improve hair regrowth in several therapeutic strategies, including reversing the pathological mechanisms, that contribute to hair loss, regeneration of hair follicles, or creating hair using the tissue-engineering approach. Although various promising stem cell approaches are progressing via pre-clinical models to clinical trials, intraoperative stem cell treatments with a one-step procedure offer a quicker result by incorporating an autologous cell source without manipulation, which may be injected by surgeons through a well-established clinical practice. Many authors have concentrated on adipose-derived stromal vascular cells due to their ability to separate into numerous cell genealogies, platelet-rich plasma for its ability to enhance cell multiplication and neo-angiogenesis, as well as human follicle mesenchymal stem cells. In this paper, the significant improvements in intraoperative stem cell approaches, from in vivo models to clinical investigations, are reviewed. The potential regenerative instruments and functions of various cell populaces in the hair regrowth process are discussed. The addition of Wnt signaling in dermal papilla cells is considered a key factor in stimulating hair growth. Mesenchymal stem cell-derived signaling and growth factors obtained by platelets influence hair growth through cellular proliferation to prolong the anagen phase (FGF-7), induce cell growth (ERK activation), stimulate hair follicle development (β-catenin), and suppress apoptotic cues (Bcl-2 release and Akt activation).

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Regenerative medicine and hair loss: how hair follicle culture has advanced our understanding of treatment options for androgenetic alopecia

Regenerative Medicine ◽

10.2217/rme.13.87 ◽

2014 ◽

Vol 9 (1) ◽

pp. 101-111 ◽

Cited By ~ 13

Author(s):

Claire A Higgins ◽

Angela M Christiano

Keyword(s):

Regenerative Medicine ◽

Hair Follicle ◽

Hair Loss ◽

Treatment Options ◽

Androgenetic Alopecia ◽

Follicle Culture

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Androgen tic alopecia (AGA) -New Approach

Bangladesh Journal of Dental Research & Education ◽

10.3329/bjdre.v5i2.24719 ◽

2015 ◽

Vol 5 (2) ◽

pp. 64-65

Author(s):

Md Ahsan Shafique

Keyword(s):

Hair Follicle ◽

Ethnic Groups ◽

Hair Loss ◽

Characteristic Pattern ◽

New Approach ◽

Dental Research ◽

Men 1 ◽

Significant Impairment ◽

Pattern Distribution ◽

Research And Education

Androgen tic alopecia is a no scarring progressive miniaturization of the hair follicle with a usual characteristic pattern distribution in genetically predisposed men 1. It is the most common hair loss disorder which causes significant impairment of life 2,3. The frequency and severity of male AGA increases with age in all ethnic groups 4.Bangladesh Journal of Dental Research and Education Vol.5(2) 2015: 64-65

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905 Dysfunction of hair follicle mesenchymal progenitors is associated with age-related hair loss

Journal of Investigative Dermatology ◽

10.1016/j.jid.2019.03.981 ◽

2019 ◽

Vol 139 (5) ◽

pp. S156

Author(s):

W. Shin ◽

N. Rosin ◽

H. Sparks ◽

S. Sinha ◽

W. Rahmani ◽

...

Keyword(s):

Hair Follicle ◽

Hair Loss ◽

Mesenchymal Progenitors ◽

Age Related

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Early Stages ofwe/we wal/walMouse Hair Morphogenesis: Light and Fluorescent Microscopy of the Whole-Mount Epidermis

BioMed Research International ◽

10.1155/2014/856978 ◽

2014 ◽

Vol 2014 ◽

pp. 1-6

Author(s):

Alexandra Rippa ◽

Olga Leonova ◽

Vladimir Popenko ◽

Andrey Vasiliev ◽

Vasily Terskikh ◽

...

Keyword(s):

Hair Follicle ◽

Hair Loss ◽

Early Stage ◽

Fluorescent Microscopy ◽

Adult Life ◽

Hair Follicles ◽

Whole Mount ◽

Interfollicular Epidermis ◽

Embryonic Morphogenesis ◽

Hair Morphogenesis

In adult skin, hair follicles cyclically self-renew in a manner that recapitulates embryonic hair follicle morphogenesis. The most common pathology of hair in adults is alopecia, which is hair loss to different extent. There are a number of murine models of alopecia including spontaneous mutations. In the present study, we worked with double homozygouswe/we wal/walmice which demonstrate symptoms closely resembling human alopecia. Using whole-mount preparations of epidermis of E18.5 embryos we show that hair follicle defects can be revealed as early as during embryonic morphogenesis in these mutants. The number of hair follicles was reduced almost 1.5-fold in mutant skin. The shape of the early stage small follicles was altered in mutant animals as compared to control ones. Additionally, follicles of mutant embryos were wider at the point of conjunction with interfollicular epidermis. We believe that the mutant mice studied represent a fascinating model to address the problem of hair loss. We demonstrated alterations in the morphogenesis of embryonic hair follicle inwe/we wal/waldouble homozygous mice developing alopecia postnatally. We suppose that incorrect morphogenesis of hair follicles during embryogenesis is closely related to alopecia in the adult life. Unveiling the mechanisms involved in altered embryogenesis may elucidate the pathogenesis of alopecia.

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What Can Complex Dietary Supplements Do for Hair Loss and How Can It Be Validly Measured—A Review

Applied Sciences ◽

10.3390/app10144996 ◽

2020 ◽

Vol 10 (14) ◽

pp. 4996

Author(s):

Nicole Braun ◽

Ulrike Heinrich

Keyword(s):

Hair Follicle ◽

Dietary Supplements ◽

Hair Loss ◽

Hair Growth ◽

Hair Cycle ◽

Active Growth ◽

Widespread Occurrence ◽

Non Invasive ◽

Anagen Phase

Hair plays a major role in perception within a society. It provides information about gender, age, health, and social status. It is therefore not surprising that those affected are exposed to great suffering due to the widespread occurrence of hair loss. As a result, the demand for new products to remedy this problem is not diminishing. Hair grows in cycles, and a hair follicle goes through several phases called the hair cycle. The active growth phase (anagen phase) lasts 2–6 years. In this state a hair follicle shows a growth of about 1 cm per month. In order to improve the existing hair status, hair should be kept in the active anagen phase as long as possible, or the transition to anagen should be stimulated. A number of reviews already describe the influence of individual active ingredients on hair growth. However, the following review describes existing studies of complex dietary supplements with their experimental weaknesses and strengths and their influence on hair loss. Also, for the determination of hair loss, it is important to use a valid method with high acceptance by the test persons. In this context, the TrichoScale® is a validated and non-invasive tool for quantifying hair loss/hair growth. Thus, it is an ideal measuring instrument to objectively quantify the effectiveness of a hair loss treatment.

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Androgenetic alopecia: new insights into the pathogenesis and mechanism of hair loss

F1000Research ◽

10.12688/f1000research.6401.1 ◽

2015 ◽

Vol 4 ◽

pp. 585 ◽

Cited By ~ 11

Author(s):

Rodney Sinclair ◽

Niloufar Torkamani ◽

Leslie Jones

Keyword(s):

Stem Cell ◽

Hair Follicle ◽

Hair Loss ◽

Cell Biology ◽

Active Role ◽

Androgenetic Alopecia ◽

Stem Cell Population ◽

Arrector Pili Muscle ◽

Biological Phenomena ◽

Organ Regeneration

The hair follicle is a complete mini-organ that lends itself as a model for investigation of a variety of complex biological phenomena, including stem cell biology, organ regeneration and cloning. The arrector pili muscle inserts into the hair follicle at the level of the bulge- the epithelial stem cell niche. The arrector pili muscle has been previously thought to be merely a bystander and not to have an active role in hair disease.Computer generated 3D reconstructions of the arrector pili muscle have helped explain why women with androgenetic alopecia (AGA) experience diffuse hair loss rather than the patterned baldness seen in men. Loss of attachment between the bulge stem cell population and the arrector pili muscle also explains why miniaturization is irreversible in AGA but not alopecia areata.A new model for the progression of AGA is presented.

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Telogen Effluvium after SARS-CoV-2 Infection: A Series of Cases and Possible Pathogenetic Mechanisms

Skin Appendage Disorders ◽

10.1159/000517223 ◽

2021 ◽

pp. 1-5

Author(s):

Alfredo Rossi ◽

Francesca Magri ◽

Alvise Sernicola ◽

Simone Michelini ◽

Gemma Caro ◽

...

Keyword(s):

Hair Follicle ◽

Inflammatory Cytokines ◽

Clinical Evaluation ◽

Median Duration ◽

Hair Loss ◽

Case Presentation ◽

Cutaneous Involvement ◽

Pathogenetic Mechanisms ◽

Larger Sample ◽

Pro Inflammatory Cytokines

Introduction: Physicians have largely studied the cutaneous involvement of coronavirus disease 2019 (COVID-19), but only few reports have focused on telogen effluvium (TE) as a possible sequela of COVID-19. We assessed 14 cases of hair loss occurring after SARS-CoV-2 infection using trichoscopy and trichogram to investigate patterns related to COVID-19. Furthermore, we discussed possible mechanisms involved in COVID-19 TE. Case Presentation: Fourteen individuals were referred to our post-COVID-19 dermatology office complaining acute hair loss after SARS-CoV-2 infection. Clinical evaluation included pull test, trichoscopy, and trichogram. COVID-19 TE occurred after a median of 2 months (range 1–3 months) following SARS-CoV-2 infection. The median duration of hair loss was 5 months (range 1–6 months). Trichoscopy showed variable but typical TE patterns. Trichogram showed different telogen/anagen ratio depending on the interval between onset of hair loss and trichological visit. Discussion/Conclusion: Our cases showed TE between 1 and 3 months after the onset of SARS-CoV-2 infection, thus earlier than classic TE. Trichoscopic features and trichogram showed no variations from classic TE. Different pathogenetic mechanisms including pro-inflammatory cytokines and direct viral damage on the hair follicle can be hypothesized; further studies on a larger sample are needed to better understand this condition.

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Bioinformatics Approach to Investigate the Genes Manifesting Alopecia Areata

10.21203/rs.3.rs-31445/v1 ◽

2020 ◽

Author(s):

Shruti Kaushal ◽

Veena Puri

Keyword(s):

Hair Follicle ◽

Hair Loss ◽

Alopecia Areata ◽

Drug Targets ◽

Homo Sapiens ◽

Model Organism ◽

Autoimmune Disorder ◽

Future Drug ◽

Dual Analysis ◽

Novel Biomarkers

Abstract Background: Alopecia areata (AA) is a type of alopecia or hair loss, which is very common in human. It is classified as an autoimmune disorder, which has a variable course. It can be either relapsing or persistent type. The persistent type is seen in patients with extensive hair loss. AA affects young people most commonly with an age less than 20 years but can also concern adults. It makes up to 4% dermatology cases in China, around 2-3% in UK and USA and 0.7% in India. Patients with alopecia have social and economic suffering due to anxiety symptoms, avoidance behavior, and social anxiety disorder, making it a very important non lethal disease to study. Methods: In the present study, microarray datasets GDS5274 and GDS5272 of AA have been re-analyzed from mouse as well as human respectively. The simultaneous analysis of model organism and patient data has provided two pronged validation approach to delineate potential biomarkers of the disease. Out of 45101 genes of model organism (Mus musculus), and 54675 genes of patient (Homo sapiens), top 100 up regulated and down regulated genes were selected and further analyzed by DAVID and Enrichr tools for KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways, GO (gene ontology) (cellular component, molecular function and biological process). Results: Four genes viz. CXCL9, CXCL10, STAT1 and CCL5 were differentially regulated in both organisms, hence can be considered as plausibly contributing in triggering the AA. The network and pathway analysis by PathwayLinker2.0 revealed the partners of these crucial genes i.e. CCR1, CCR5, IGFBP7, VCAN, DPP4, CCR3, CXCR3 through which these genes might coordinate to manifest hair fall.Conclusions: The dual analysis approach has helped to generate plausible novel biomarkers of the disease for diagnostic and therapeutic approach. Stimulation of any of these biomarkers by various triggers can damage hair follicle. These genes can be targeted therapeutically to halt the hair follicle damage by inhibiting their expression hence, providing novel future drug targets for AA.

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