Human hair growth ex vivo is correlated with in vivo hair growth: selective categorization of hair follicles for more reliable hair follicle organ culture

AbstractShikimic acid (SA) has recently been found to be a major component of plant stem cells. The exact effects of SA on human hair follicles (HFs) is unknown. The purpose of this study was to examine the effects of SA on hair growth. We investigated the effect of SA on an in vivo C57BL/6 mouse model. We examined the expression of mannose receptor (MR), which is a known receptor of SA, in human HFs and the effect of SA on human dermal papilla cells (hDPCs), outer root sheath cells (hORSCs), and on ex vivo human hair organ culture. SA significantly prolonged anagen hair growth in the in vivo mouse model. We confirmed expression of the MR in human HFs, and that SA increased the proliferation of hDPCs and hORSCs. It was found that SA enhanced hair shaft elongation in an ex vivo human hair organ culture. SA treatment of hDPCs led to increased c-myc, hepatocyte growth factor, keratinocyte growth factor and vascular endothelial growth factor levels and upregulation of p38 MAPK and cAMP response element-binding protein levels. Our results show that SA promotes hair growth and may serve as a new therapeutic agent in the treatment of alopecia.

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Increased Expression of Zyxin and Its Potential Function in Androgenetic Alopecia

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2020.582282 ◽

2021 ◽

Vol 8 ◽

Author(s):

Qingmei Liu ◽

Xiangguang Shi ◽

Yue Zhang ◽

Yan Huang ◽

Kai Yang ◽

...

Keyword(s):

Stem Cell ◽

Hair Follicle ◽

Hair Growth ◽

Ex Vivo ◽

Cell Activity ◽

Hair Follicles ◽

Androgenetic Alopecia ◽

Pcr Analysis

Androgenetic alopecia (AGA) is the most common progressive form of hair loss, occurring in more than half of men aged > 50 years. Hair follicle (HF) miniaturization is a feature of AGA, and dermal papillae (DP) play key roles in hair growth and regeneration by regulating follicular cell activity. Previous studies have revealed that adhesion signals are important factors in AGA development. Zyxin (ZYX) is an actin-interacting protein that is essential for cell adhesion and migration. The aim of this research was to investigate the expression and potential role of ZYX in AGA. Real-time polymerase chain reaction (RT-PCR) analysis revealed that ZYX expression was elevated in the affected frontal HF of individuals with AGA compared to unaffected occipital HF. Moreover, increased ZYX expression was also observed within DP using immunofluorescence staining. Our in vivo results revealed that ZYX knockout mice showed enhanced hair growth and anagen entry compared to wild-type mice. Reducing ZYX expression in ex vivo cultured HFs by siRNA resulted in the enhanced hair shaft production, delayed hair follicle catagen entry, increased the proliferation of dermal papilla cells (DPCs), and upregulated expression of stem cell-related proteins. These results were further validated in cultured DPCs in vitro. To further reveal the mechanism by which ZYX contributes to AGA, RNA-seq analysis was conducted to identify gene signatures upon ZYX siRNA treatment in cultured hair follicles. Multiple pathways, including focal adhesion and HIF-1 signaling pathways, were found to be involved. Collectively, we discovered the elevated expression of ZYX in the affected frontal hair follicles of AGA patients and revealed the effects of ZYX downregulation on in vivo mice, ex vivo hair follicles, and in vitro DPC. These findings suggest that ZYX plays important roles in the pathogenesis of AGA and stem cell properties of DPC and may potentially be used as a therapeutic target in AGA.

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Macrophage-Stimulating Protein Promotes Hair Growth Ex Vivo and Induces Anagen from Telogen Stage Hair Follicles In Vivo

Journal of Investigative Dermatology ◽

10.1111/j.0022-202x.2004.22712.x ◽

2004 ◽

Vol 123 (1) ◽

pp. 34-40 ◽

Cited By ~ 20

Author(s):

Kevin J. McElwee ◽

Andrea Huth ◽

Sabine Kissling ◽

Rolf Hoffmann

Keyword(s):

Hair Growth ◽

Ex Vivo ◽

Hair Follicles ◽

Macrophage Stimulating Protein

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Methods in hair research: how to objectively distinguish between anagen and catagen in human hair follicle organ culture

Experimental Dermatology ◽

10.1111/j.1600-0625.2009.00939.x ◽

2010 ◽

Vol 19 (3) ◽

pp. 305-312 ◽

Cited By ~ 84

Author(s):

Jennifer Elisabeth Kloepper ◽

Koji Sugawara ◽

Yusur Al-Nuaimi ◽

Erzsébet Gáspár ◽

Nina van Beek ◽

...

Keyword(s):

Organ Culture ◽

Hair Follicle ◽

Human Hair ◽

Human Hair Follicle ◽

Hair Follicle Organ Culture

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Assessment of Hair Growth Treatment with the Consciousness Energy Healing Treated Williams Medium E Using Mouse Vibrissae Hair Follicle Organ Culture

Journal of Dermatologic Research And Therapy ◽

10.14302/issn.2471-2175.jdrt-18-2520 ◽

2019 ◽

Vol 1 (3) ◽

pp. 12-19

Author(s):

Mahendra Kumar Trivedi ◽

Snehasis Jana

Keyword(s):

Organ Culture ◽

Hair Follicle ◽

Test Item ◽

Hair Growth ◽

Sexual Communication ◽

Growth Promotion ◽

Growth Promoter ◽

Energy Healing ◽

Hair Follicle Organ Culture

Hair is playing an interesting part in human for social and sexual communication. Loss of hair follicle leads to various skin disorders. For this consequence, the present study has investigated the potential of the Biofield Energy Healing (The Trivedi Effect®) Treated test item (William’s Medium E) on the vibrissae hair follicle organ culture cells for the assessment of hair cell growth and development in vitro. The test item was divided into two parts. One part was defined as the untreated test item, where no Biofield Energy Treatment provided, while the other part was defined as the Biofield Energy Treated test item, which received the Biofield Energy Healing Treatment by renowned Biofield Energy Healer, Mahendra Kumar Trivedi. The study parameters like bulb thickness and formation of telogen were assessed using cell-based assay with the help of UTHSCSA Image tool version 3. The experimental results showed that the untreated test item group showed 20.9% and 28.2% increased bulb thickness on day 5 and 7, respectively compared to the day 1, while did not produce telogen follicles upto day 7. Besides, the percentage of telogen follicle was found as 43%, 57%, and 71% on day 3, 5, and 7, respectively of the Biofield Energy Treated test item group compared to the day 1. The overall results demonstrated that the Biofield Energy Treatment has the potential for hair growth promotion as evident via increased the formation of telogen. Therefore, the Biofield Energy Healing (The Trivedi Effect®) Treatment might be useful as a hair growth promoter for various treatment of skin injuries and skin-related disorders like necrotizing fasciitis, actinic keratosis, sebaceous cysts, diaper rash, decubitus ulcer etc.

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Limitations of human occipital scalp hair follicle organ culture for studying the effects of minoxidil as a hair growth enhancer

Experimental Dermatology ◽

10.1111/j.0906-6705.2004.00207.x ◽

2004 ◽

Vol 13 (10) ◽

pp. 635-642 ◽

Cited By ~ 24

Author(s):

Markus Magerl ◽

Ralf Paus ◽

Nilofer Farjo ◽

Sven Muller-Rover ◽

Eva M. J. Peters ◽

...

Keyword(s):

Organ Culture ◽

Hair Follicle ◽

Hair Growth ◽

Scalp Hair ◽

Hair Follicle Organ Culture

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Human hair growth in vitro

Journal of Cell Science ◽

10.1242/jcs.97.3.463 ◽

1990 ◽

Vol 97 (3) ◽

pp. 463-471

Author(s):

M.P. Philpott ◽

M.R. Green ◽

T. Kealey

Keyword(s):

Hair Follicle ◽

Human Hair ◽

Subcutaneous Fat ◽

Hair Shaft ◽

Hair Follicles ◽

Anagen Hair ◽

Scalpel Blade ◽

Thymidine Autoradiography

We report for the first time the successful maintenance and growth of human hair follicles in vitro. Human anagen hair follicles were isolated by microdissection from human scalp skin. Isolation of the hair follicles was achieved by cutting the follicle at the dermo-subcutaneous fat interface using a scalpel blade. Intact hair follicles were then removed from the fat using watchmakers' forceps. Isolated hair follicles maintained free-floating in supplemented Williams E medium in individual wells of 24-well multiwell plates showed a significant increase in length over 4 days. The increase in length was seen to be attributed to the production of a keratinised hair shaft, and was not associated with the loss of hair follicle morphology. [methyl-3H]thymidine autoradiography confirmed that in vitro the in vivo pattern of DNA synthesis was maintained; furthermore, [35S]methionine labelling of keratins showed that their patterns of synthesis did not change with maintenance. The importance of this model to hair follicle biology is further demonstrated by the observations that TGF-beta 1 has a negative growth-regulatory effect on hair follicles in vitro and that EGF mimics the in vivo depilatory effects that have been reported in sheep and mice.

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Sustained Human Hair Follicle Growth Ex Vivo in a Glycosaminoglycan Hydrogel Matrix

International Journal of Molecular Sciences ◽

10.3390/ijms20071741 ◽

2019 ◽

Vol 20 (7) ◽

pp. 1741 ◽

Cited By ~ 1

Author(s):

Sandra Fernández-Martos ◽

María Calvo-Sánchez ◽

Karla García-Alonso ◽

Begoña Castro ◽

Bita Hashtroody ◽

...

Keyword(s):

Hair Follicle ◽

Human Hair ◽

Wound Repair ◽

Ex Vivo ◽

Hair Follicles ◽

Stem Cell Markers ◽

Follicle Growth ◽

Human Hair Follicle ◽

Hydrogel Matrix ◽

Hair Follicle Growth

Glycosaminoglycans (GAGs) and associated proteoglycans have important functions in homeostatic maintenance and regenerative processes (e.g., wound repair) of the skin. However, little is known about the role of these molecules in the regulation of the hair follicle cycle. Here we report that growing human hair follicles ex vivo in a defined GAG hydrogel mimicking the dermal matrix strongly promotes sustained cell survival and maintenance of a highly proliferative phenotype in the hair bulb and suprabulbar regions. This significant effect is associated with the activation of WNT/β-catenin signaling targets (CCDN1, AXIN2) and with the expression of stem cell markers (CK15, CD34) and growth factors implicated in the telogen/anagen transition (TGFβ2, FGF10). As a whole, these results point to the dermal GAG matrix as an important component in the regulation of the human hair follicle growth cycle, and to GAG-based hydrogels as potentially relevant modulators of this process both in vitro and in vivo.

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