• Molecules and Cells
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• v.46 no.10
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• pp.573-578
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• 2023

The mammalian skin contains hair follicles, which are epidermal appendages that undergo periodic cycles and exhibit mini-organ features, such as discrete stem cell compartments and different cellular components. Wound-induced hair follicle neogenesis (WIHN) is the remarkable ability to regenerate hair follicles after large-scale wounding and occurs in several adult mammals. WIHN is comparable to embryonic hair follicle development in its processes. Researchers are beginning to identify the stem cells that, in response to wounding, develop into neogenic hair follicles, as well as to understand the functions of immune cells, mesenchymal cells, and several signaling pathways that are essential for this process. WIHN represents a promising therapeutic approach to the reprogramming of cellular states for promoting hair follicle regeneration and preventing scar formation. In the scope of this review, we investigate the contribution of several cell types and molecular mechanisms to WIHN.

• Applied Microscopy
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• v.27 no.3
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• pp.321-332
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• 1997

The dermal papilla is known to playa major role in influencing the form and dynamics of the hair follicle, which probably involves regulatory substances crossing the basal lamina. But little is known about the junctions between the dermal papilla and the surrounding epithelial cells of the hair bulb, or between the connective tissue and the epithelial cells on the outside of the hair follicle. This study was performed to identify the ultrastructural differences between dermoepidermal junction of the skin and connective tissue-epithelial junctions on the outside of the hair follicle and around the dermal papilla of normal anagen hair follicles in the human fetal scalp skin. Electron microscopic findings of dermoepidermal junction in scalp skin showed that basal lamina was very irregular and undulated, and it contained many attachment plaques of hemidesmosomes with sub-basal dense plates, tonofilaments, and anchoring filaments. Also invaginations of plasma membrane of basal keratinocytes were seen. There were clear differences both on the outside of the follicle and around the dermal papilla as compared with similar junction in the skin. In particular, neither hemidesmosomes nor tonofilaments, as seen in dermoepidermal junction, were observed in the dermal papilla. Also attachment plaque, sub-basal dense plate and anchoring filaments were not observed at the junction on the outside of the follicle and the dermal papilla. There were some differences between connective tissue-epithelial junctions on the outside of the hair follicle and around the dermal papilla, ie, smoothness of basal lamina and orthogonal arrangement of collagen fibers were seen in the outside of hair follicle, but not in the dermal papilla. These results indicate that the mechanical connection between the hair follicle and the connective tissue component is much weaker than that between the corresponding components in skin, and it reflects the dynamic processes during the anagen phase of the hair follicle compared to the relatively permanent state of the epidermis.

• BMB Reports
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• v.56 no.1
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• pp.2-9
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• 2023

Hair follicles in the skin undergo cyclic rounds of regeneration, degeneration, and rest throughout life. Stem cells residing in hair follicles play a pivotal role in maintaining tissue homeostasis and hair growth cycles. Research on hair follicle aging and age-related hair loss has demonstrated that a decline in hair follicle stem cell (HFSC) activity with aging can decrease the regeneration capacity of hair follicles. This review summarizes our understanding of how age-associated HFSC intrinsic and extrinsic mechanisms can induce HFSC aging and hair loss. In addition, we discuss approaches developed to attenuate ageassociated changes in HFSCs and their niches, thereby promoting hair regrowth.

• Journal of Ginseng Research
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• v.40 no.2
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• pp.169-175
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• 2016

Background: Chemotherapy-induced alopecia (CIA) is one of the most distressing side effects for patients undergoing chemotherapy. This study evaluated the protective effect of Korean Red Ginseng (KRG) on CIA in a well-established in vitro human hair follicle organ culture model as it occurs in vivo. Methods: We examined whether KRG can prevent premature hair follicle dystrophy in a human hair follicle organ culture model during treatment with a key cyclophosphamide metabolite, 4-hydroperoxycyclophosphamide (4-HC). Results: 4-HC inhibited human hair growth, induced premature catagen development, and inhibited proliferation and stimulated apoptosis of hair matrix keratinocytes. In addition, 4-HC increased p53 and Bax protein expression and decreased Bcl2 protein expression. Pretreatment with KRG protected against 4-HC-induced hair growth inhibition and premature catagen development. KRG also suppressed 4-HC-induced inhibition of matrix keratinocyte proliferation and stimulation of matrix keratinocyte apoptosis. Moreover, KRG restored 4-HC-induced p53 and Bax/Bcl2 expression. Conclusion: Overall, our results indicate that KRG may protect against 4-HC-induced premature catagen development through modulation of p53 and Bax/Bcl2 expression.

• Experimental and Molecular Medicine
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• v.50 no.12
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• pp.5.1-5.15
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• 2018

Targeting hair follicle regeneration has been investigated for the treatment of hair loss, and fundamental studies investigating stem cells and their niche have been described. However, knowledge of stem cell metabolism and the specific regulation of bioenergetics during the hair regeneration process is currently insufficient. Here, we report the hair regrowth-promoting effect of a newly synthesized novel small molecule, IM176OUT05 (IM), which activates stem cell metabolism. IM facilitated stemness induction and maintenance during an induced pluripotent stem cell generation process. IM treatment mildly inhibited mitochondrial oxidative phosphorylation and concurrently increased glycolysis, which accelerated stemness induction during the early phase of reprogramming. More importantly, the topical application of IM accelerated hair follicle regeneration by stimulating the progression of the hair follicle cycle to the anagen phase and increased the hair follicle number in mice. Furthermore, the stem cell population with a glycolytic metabotype appeared slightly earlier in the IM-treated mice. Stem cell and niche signaling involved in the hair regeneration process was also activated by the IM treatment during the early phase of hair follicle regeneration. Overall, these results show that the novel small molecule IM promotes tissue regeneration, specifically in hair regrowth, by restructuring the metabolic configuration of stem cells.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.49 no.1
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• pp.75-85
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• 2023

This study was conducted to assess the effect of heptapeptide, composed of seven amino acids, on the activation of human hair cells isolated from human hair follicles. We have confirmed that the heptapeptide could bind to Lgr5 from the results of surface plasmon resonance (SPR) analysis. Heptapeptide enhanced the proliferation of human hair follicle dermal papilla cells (HHFDPCs) in a dose dependent manner. It induced the protein level of nuclear β-catenin, and the expressions of β-catenin downstream target genes, including LEF1, Cyc-D1 and c-Myc, in HHFDPCs. Heptapeptide significantly induced the phosphorylation of Akt and ERK, and the mRNA expressions of growth factors, including hepatocyte growth factor (HGF), keratinocyte growth factor (KGF) and vascular endothelial growth factor (VEGF), in HHFDPCs. In addition, heptapeptide significantly increased mRNA expression levels of differentiation-related transcription factors of human hair germinal matrix cells (HHGMCs) and differentiation markers of human hair outer root sheath cells (HHORSCs). Additionally, we investigated the effect of heptapeptide on human hair follicle stem cells (HHFSCs) differentiation and found that the heptapeptide reduced the mRNA and protein levels of stem cell markers, while it increased those levels of differentiation markers. These results have indicated that the heptapeptide promotes proliferation or differentiation of various types of hair follicle constituent cells through the induction of Wnt/β-catenin signaling. From the results, we have suggested that the heptapeptide in this study could be applied as a new functional material for the improvement of hair growth and alopecia.

• Journal of Physiology & Pathology in Korean Medicine
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• v.25 no.4
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• pp.674-682
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• 2011

The present study was undertaken to investigate the effect of acupuncture & moxibustion therapy on the hair follicle growth of skin 5 days and 10 days by macroscopic, microscopic and immunohistochemical methods. The results were as follows : Macroscopic hair follicle growth of plum-blossom needle treated group and strong moxibustion treated group was more increase than that of control group. Microscopic hair follicle growth of plum-blossom needle treated group and strong moxibustion treated group was hair growing cycle, anagen phase VI and that of control group and weak moxibustion treated group was hair growing cycle, anagen phase IV. Immunohistochemical observations on the expression of various growth factors, enzyme and receptor in hair follicle cycle after local treatment of acupuncture & moxibustion therapy are as follows: Expression of fibroblast growth factor was more intense in epidermis in plum-blossom needle treated group, epidermis and secondary hair germ cells in strong moxibustion treated group than control group. Expression of epidermal growth factor was more intense in epidermis in all experimental groups, and secondary hair germ cells in moxibustion treated group than control group. Expression of c-kit receptor was more intense in epidermis, secondary hair germ cells, outer root sheath in all experimental groups than control group. Expression of protein kinase C-${\alpha}$ was more intense in epidermis, secondary hair germ cells, outer root sheath in all experimental groups than control group. Expression of vascular endothelial growth factor was more intense in epidermis, bulge, secondary hair germ cells, outer root sheath in plum-blossom needle treated group and strong moxibustion treated group than control group. We concluded that acupuncture & moxibustion therapy related to the expression of various growth factors, enzymes and receptor on the hair growth cycle for hair growth.

• Journal of the Korean Society of Industry Convergence
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• v.17 no.3
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• pp.178-183
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• 2014

The objective of this study is to find out the effect of yeast on hair loss treatment and the role of hair follicle stem cell activator, which is important in hair growth. The authors have recently produced a substance, which has no disgusting odor, does not precipitates and does not easily corrupt, to use instead of yeast acquired from raw rice wine(Makgeolli). The substance is named Yeast Constituent Extract(YCE). In this research, the Produced YCE was applied on the hair loss area of 10 Androgenic alopecia patients, twice every day for 6 months, in order to test the effect of hair loss treatment and the role of stem cell activator. As a result, all of the patients showed a significant growth of hair after 3 months of test, and showed much more growing, thickening and strengthening of hair after 6 months. As a result of measuring the number of hair strings in the same scalp region of the patients after 6 months, it is found that the density of hair has increased, indicating that the hair loss treatment was effective. Also the hair follicle stem cell was isolated from the patients and the contents of growth factors (IGF, VEGF, FGF, HGF) derived from hair follicle stem cell were measured with ELISA. As result, the amount is found to be about 10 times greater than before the test. The hair follicle stem cell contains many growth factors that affect growth of hair, so it takes a highly important role in hair loss treatment. The YCE that the authors have produced was found to be effective in increasing the contents of growth factors that are derived from hair follicle stem cell. Thus it can be inferred that the YCE plays a role as a stem cell activator that activates the hair follicle stem cells. In conclusion, the YCE is considered to be highly effective for hair loss treatment and to have a role as a stem cell activator.

• Development and Reproduction
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• v.25 no.4
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• pp.279-291
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• 2021

Hair loss is one of the most common chronic diseases, with a detrimental effect on a patient's psychosocial life. Hair loss results from damage to the hair follicle (HF) and/or hair regeneration cycle. Various damaging factors, such as hereditary, inflammation, and aging, impair hair regeneration by inhibiting the activation of hair follicle stem cells (HFSCs) and dermal papilla cells (DPCs). Formyl peptide receptor 2 (FPR2) regulates the inflammatory response and the activity of various types of stem cells, and has recently been reported to have a protective effect on hair loss. Given that stem cell activity is the driving force for hair regeneration, we hypothesized that FPR2 influences hair regeneration by mediating HFSC activity. To prove this hypothesis, we investigated the role of FPR2 in hair regeneration using Fpr2 knockout (KO) mice. Fpr2 KO mice were found to have excessive hair loss and abnormal HF structures and skin layer construction compared to wild-type (WT) mice. The levels of Sonic hedgehog (Shh) and β-catenin, which promote HF regeneration, were significantly decreased, and the expression of bone morphogenetic protein (Bmp)2/4, an inhibitor of the anagen phase, was significantly increased in Fpr2 KO mice compared to WT mice. The proliferation of HFSCs and DPCs was significantly lower in Fpr2 KO mice than in WT mice. These findings demonstrate that FPR2 impacts signaling molecules that regulate HF regeneration, and is involved in the proliferation of HFSCs and DPCs, exerting a protective effect on hair loss.

• Korea Journal of Cosmetic Science
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• v.1 no.1
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• pp.11-18
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• 2019

Caffeine is widely used in cosmetics and hair care products. Although its efficacy in stimulating hair growth has been confirmed in recent studies, its mechanism of action remains unelucidated. The present study aimed to determine the effects of caffeine on hair growth, with a focus on intracellular hair follicle activity. Experiments included in vitro and ex vivo tests, and a clinical study. Caffeine enhanced the cellular activity and potassium channel opening. It also promoted human hair follicle elongation. Immunohistochemical staining showed that the Ki-67 signal was significantly higher in cells treated with caffeine. These efficacies of caffeine were comprehensively demonstrated in clinical results, wherein caffeine-containing shampoo improved hair density after 24 weeks of testing. Collectively, the results of this study demonstrated that caffeine promoted hair growth and inhibited the progression of hair loss by enhancing intracellular activity of hair follicles.