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Objective: Dermal papilla cells (DPCs) play a pivotal role in hair follicle development and can modulate melanogenesis in melanocytes (MCs) through their microenvironment. Our previous studies have demonstrated that the levels of exosomal miR-222-3p derived from DPCs of white Rex rabbits are significantly higher than those of black Rex rabbits. However, the specific role and underlying molecular mechanisms of exosomal miR-222-3p in melanogenesis remain elusive. Methods: DPCs and MCs were isolated from hair follicles of Rex rabbits and identified using western blotting (WB) and immunofluorescent staining. Exosomes derived from DPCs (DPCs-exos) were characterized using nanoparticle tracking analysis, transmission electron microscopy, and WB. To investigate cell-cell crosstalk mediated by exosomes, MCs were co-cultured with CM-Dil-labeled DPCs-exos. The expression of miR-222-3p in skin tissue and exosomes was quantitatively assessed using quantitative real-time polymerase chain reaction. The transmission of DPCs-secreted exosomal miR-222-3p to MCs was demonstrated using Cy3-labeled miR-222-3p in conjunction with transwell assays. The impact of miR-222-3p on melanin synthesis was evaluated using the NaOH method, cell counting kit-8, and annexin V-fluorescein isothiocyanate/propidium iodide assays. Sex determining region Y-box 10 (SOX10), a potential target gene regulated by miR-222- 3p, was validated using a dual-luciferase reporter assay, site-specific mutation, and WB. Results: Increased levels of miR-222-3p were observed in the skin and DPCs-exos of white Rex rabbits compared to those of black Rex rabbits. Effective internalization of CM-Dillabeled DPCs-exos by MCs was observed. Furthermore, exosomal miR-222-3p derived from DPCs was transferred to MCs. Functionally, miR-222-3p significantly inhibited MCs proliferation, induced apoptosis and inhibited melanin synthesis. SOX10 was confirmed as a direct target of miR-222-3p in this regulatory cascade. Conclusion: The findings demonstrate that exosomal miR-222-3p, derived from DPCs, suppresses melanogenesis in MCs by targeting SOX10, thus unveiling a novel mechanism of exosome involvement in melanogenesis. [ABSTRACT FROM AUTHOR]

The hair follicle is a complex of mesenchymal and epithelial cells acquiring different properties and characteristics responsible for fulfilling its inductive and regenerative role. The epidermal and dermal crosstalk induces morphogenesis and maintains hair follicle cycling properties. The hair follicle is enriched with pluripotent stem cells, where dermal papilla (DP) cells and dermal sheath (DS) cells constitute the dermal compartment and the epithelial stem cells existing in the bulge region exert their regenerative role by mediating the epithelial–mesenchymal interaction (EMI). Many studies have developed and focused on various methods to optimize the EMI through in vivo and in vitro approaches for hair regeneration. The culturing of human hair mesenchymal cells resulted in the loss of trichogenicity and inductive properties of DP cells, limiting their potential application in de novo hair follicle generation in vivo. Epithelial stem cells derived from human hair follicles are challenging to isolate and culture, making it difficult to obtain enough cells for hair regeneration purposes. Mesenchymal stem cells and epithelial stem cells derived from human hair follicles lose their ability to form hair follicles during culture, limiting the study of hair follicle formation in vivo. Therefore, many attempts and methods have been developed to overcome these limitations. Here, we review the possible and necessary cell methods and techniques used for human hair follicle regeneration and the restoration of hair follicle cell inductivity in culture. [ABSTRACT FROM AUTHOR]

Background: Deer placenta extract (DPE), rich in bioactive macromolecules, promotes regenerative effects in both normal and damaged cells. However, effective delivery of these macromolecules through the skin remains a challenge. Objectives: To investigate the potential of DPE in regenerating hair cells and to develop a nanoniosome (NS) and microspicule (MS) formulation as a promising transfollicular delivery system. Methods: The bioactivity of DPE was assessed in human follicle dermal papilla (HFDP) cells, including cells damaged by chemotherapy. The NS-MS formulation was designed to deliver biomacromolecules from DPE into skin and hair follicles. Results: DPE at 2000 µg/mL exhibited no cytotoxicity and significantly enhanced proliferation in both normal and cisplatin-treated HFDP cells. The DPE-loaded NSs displayed nanovesicles with a uniform size distribution and a negative surface charge. When incorporated into the MS gel, NS-MS demonstrated a synergistic effect, significantly enhancing the transdermal and transfollicular delivery of macromolecular protein into the skin layers and hair follicles. Conclusions: DPE promoted hair cell proliferation and facilitated the recovery of hair cells damaged by chemotherapy, especially when formulated into the NS-MS system, which effectively delivered bioactive macromolecules to the target site. This suggests its potential role in promoting hair regrowth. [ABSTRACT FROM AUTHOR]

Dermal papilla cells (DPCs) regulate the hair cycle and play important roles in hair growth and regeneration. Alopecia is a pathology caused by a deregulation in the hair cycle phases. Currently, the use of physical therapies such as radiofrequency (RF) as an alternative to pharmacological treatment is increasing. Electrical stimulation by capacitive resistive electrical transfer (CRET) is one of these therapies. The objective of the present study was to analyze the effect of RF-CRET currents on DPCs. Cells were treated with subthermal 448 kHz CRET currents with two different types of signals: standard (CRET-STD) or modulated (CRET-MOD). Viability (XTT Assay), proliferation (Ki67 and ERK1/2), apoptosis (p53 and caspase 3), differentiation (β-catenin and α-SMA), and anagen markers (versican and PPARγ) were analyzed by immunofluorescence and immunoblot. CRET caused effects on the proliferation and survival of DPCs associated with increases in the expression of p-MAPK-ERK1/2, cyclin D1, and decreases in the expression of p53 and caspase 3. Also, CRET caused significant transient increases in the expression of β-catenin, involved in hair growth, and in the expression of anagen phase markers such as versican and PPARγ related to hair follicle maintenance. The present study highlights the ability of treatment with CRET therapy to cause molecular alterations in DPC involved in hair regeneration. [ABSTRACT FROM AUTHOR]

Abstract Background The use of mesenchymal stem cells (MSCs) is recognized as a promising strategy for the treatment of androgenetic alopecia (AGA). However, the underlying mechanism remains to be explored. Here, we evaluated the therapeutic effects and potential mechanisms of the use of human umbilical cord mesenchymal stem cells (hUCMSCs) in dihydrotestosterone (DHT)-induced AGA models in vivo and in vitro. Methods Intradermal transplantation of hUCMSCs was performed in AGA model mice and therapeutic effects were evaluated using histological and immunofluorescence staining. Transwell assays were used for co-culture of hUCMSCs and dermal papilla cells (DPCs), and communication was assessed using RT-qPCR, immunofluorescence, and apoptosis analysis. Interactions between DPCs and hair follicle stem cells (HFSCs) were investigated using RT-qPCR, EdU assays, and cell cycle analysis. Results Treatment of AGA mice with hUCMSCs promoted hair growth, HFs density, skin thickness, and anagen phase activation, while inhibiting DPCs apoptosis, and promoting HFSCs proliferation. In vitro, hUCMSCs activated Wnt/β-catenin signaling in DPCs via Wntless (Wls), while stimulating growth factor secretion and HFSCs proliferation. Blocking β-catenin degradation with MSAB increased DPCs apoptosis, reduced growth factor secretion, and retarded HFSCs proliferation. Conclusion hUCMSCs promoted hair regeneration in AGA model mice. This was found to be dependent on reducing DPCs apoptosis, thereby relieving the inhibitory effects of DPCs on the growth of HFSCs. The activation of the Wnt/β-catenin signaling pathway was shown to play a crucial role in the promotion of hair growth by hUCMSCs in AGA mice.

Objective To explore the protective role of DNA damage induced transcription factor 4 (DDIT4) in oxidative stress injury in dermal papilla cells and its underlying mechanisms. Methods Dermal papilla cells were exposed to UVA and H2O2 to establish cellular model of oxidative stress. CCK-8 assay was used to detect cell viability under different treatment conditions, and the production of intracellular reactive oxygen species (ROS) was detected using 2′, 7′-dichlorofluorescein diacetate (DCFH-DA). Autophagic vesicles were observed with electron microscopy. Western blotting was employed to measure the expression of DDIT4 and autophagy-related molecules, including microtubule-associated protein 1 light chain 3 (LC3), ubiquitin-binding protein (P62), mammalian target of rapamycin (mTOR), and p-mTOR. Results UVA and H2O2 resulted in more production of ROS (P < 0.05) and decreased viability of dermal papilla cells (P < 0.05). DDIT4 expression was increased in dermal papilla cells under oxidative stress (P < 0.05), and the antioxidant N-acetyl-L-cysteine (NAC) could effectively inhibit this effect (P < 0.05). After treatment with UVA or H2O2, cell autophagy was enhanced in dermal papilla cells, characterized by an increase in the number of autophagosomes and an increased LC3Ⅱ/Ⅰ ratio (P < 0.05), a decrease in P62 expression (P < 0.05), and 3-methyladenine (3-MA) blocking autophagy led to further reduced cell viability (P < 0.05) and increased intracellular ROS production (P < 0.05). Conversely, rapamycin (RAPA) increased autophagy level and improved the viability of dermal papilla cells under oxidative conditions (P < 0.05), and reduced the generation of intracellular ROS (P < 0.05). Additionally, down-regulation of DDIT4 weakened autophagy in dermal papilla cells under oxidative stress, reduced LC3Ⅱ/Ⅰ (P < 0.05), increased p-mTOR/mTOR and P62 (P < 0.05), inhibited cell viability (P < 0.05), and enhanced intracellular ROS production (P < 0.05). Conclusion DDIT4 may alleviate oxidative stress injury in dermal papilla cells through autophagy.

Abstract Background Hair follicles (HFs) are dynamic structures which are readily accessible within the skin that contain various pools of stem cells with broad regenerative potential, such as dermal papilla cells (DPCs), dermal sheath cells, and epithelial HF stem cells. DPCs act as signalling centres for HF regeneration. The current method for isolating human DPCs are inefficient. These methods struggle to obtain freshly isolated original DPCs and do not maintain the characteristics of DPCs effectively. Methods In this study, two simple but more efficient methods were explored. Force-triggered density gradient sedimentation (FDGS) and cocktail enzyme digestion treatment (CEDT) were used to isolate purified DP spheres from human HFs, obtaining purified freshly isolated original DPCs from DP spheres. The expression profiles of isolated DPCs were tested, and gene expression of DPC-specific markers were analyzed using immunofluorescence staining, RT-qPCR and western blot. Results The 10% Ficoll PM400 was determined as the optimal concentration for FDGS method. Primary DPCs, DSCs and HFSCs were isolated simultaneously using the FDGS and CEDT method. The expression profiles of fresh DPCs isolated using the FDGS and CEDT methods were similar to those of traditionally isolated DPCs. DP-specific markers were expressed at significantly higher levels in freshly isolated DPCs than in traditionally isolated DPCs. Conclusions Compared to traditional methods, the presented laboratory protocols were able to isolate fresh DPCs with high efficiency, thereby improving their research potential.

Background: The use of mesenchymal stem cells (MSCs) is recognized as a promising strategy for the treatment of androgenetic alopecia (AGA). However, the underlying mechanism remains to be explored. Here, we evaluated the therapeutic effects and potential mechanisms of the use of human umbilical cord mesenchymal stem cells (hUCMSCs) in dihydrotestosterone (DHT)-induced AGA models in vivo and in vitro. Methods: Intradermal transplantation of hUCMSCs was performed in AGA model mice and therapeutic effects were evaluated using histological and immunofluorescence staining. Transwell assays were used for co-culture of hUCMSCs and dermal papilla cells (DPCs), and communication was assessed using RT-qPCR, immunofluorescence, and apoptosis analysis. Interactions between DPCs and hair follicle stem cells (HFSCs) were investigated using RT-qPCR, EdU assays, and cell cycle analysis. Results: Treatment of AGA mice with hUCMSCs promoted hair growth, HFs density, skin thickness, and anagen phase activation, while inhibiting DPCs apoptosis, and promoting HFSCs proliferation. In vitro, hUCMSCs activated Wnt/β-catenin signaling in DPCs via Wntless (Wls), while stimulating growth factor secretion and HFSCs proliferation. Blocking β-catenin degradation with MSAB increased DPCs apoptosis, reduced growth factor secretion, and retarded HFSCs proliferation. Conclusion: hUCMSCs promoted hair regeneration in AGA model mice. This was found to be dependent on reducing DPCs apoptosis, thereby relieving the inhibitory effects of DPCs on the growth of HFSCs. The activation of the Wnt/β-catenin signaling pathway was shown to play a crucial role in the promotion of hair growth by hUCMSCs in AGA mice. [ABSTRACT FROM AUTHOR]

Background: Hair follicles (HFs) are dynamic structures which are readily accessible within the skin that contain various pools of stem cells with broad regenerative potential, such as dermal papilla cells (DPCs), dermal sheath cells, and epithelial HF stem cells. DPCs act as signalling centres for HF regeneration. The current method for isolating human DPCs are inefficient. These methods struggle to obtain freshly isolated original DPCs and do not maintain the characteristics of DPCs effectively. Methods: In this study, two simple but more efficient methods were explored. Force-triggered density gradient sedimentation (FDGS) and cocktail enzyme digestion treatment (CEDT) were used to isolate purified DP spheres from human HFs, obtaining purified freshly isolated original DPCs from DP spheres. The expression profiles of isolated DPCs were tested, and gene expression of DPC-specific markers were analyzed using immunofluorescence staining, RT-qPCR and western blot. Results: The 10% Ficoll PM400 was determined as the optimal concentration for FDGS method. Primary DPCs, DSCs and HFSCs were isolated simultaneously using the FDGS and CEDT method. The expression profiles of fresh DPCs isolated using the FDGS and CEDT methods were similar to those of traditionally isolated DPCs. DP-specific markers were expressed at significantly higher levels in freshly isolated DPCs than in traditionally isolated DPCs. Conclusions: Compared to traditional methods, the presented laboratory protocols were able to isolate fresh DPCs with high efficiency, thereby improving their research potential. [ABSTRACT FROM AUTHOR]

Objective We tried to investigate the effects of human umbilical cord mesenchymal stem cell exosomes （hUCMSC-Exos） on the proliferation of human dermal papilla cells （HDPCs） and the mechanism of hUCMSC-Exos promoting hair growth. Methods HDPCs were isolated using two-step enzymatic method and cultured in vitro. Human umbilical cord mesenchymal stem cells （hUC-MSCs） were cultured. Cell culture supernatant was collected, and exosomes were isolated and extracted using high-speed centrifugation. Electron microscopy, particle size, and surface marker identification were performed on them. Dihydrotestosterone （DHT） induces HDPCs and establishment of an androgenic alopecia cell model. Co-culture hUCMSC-Exos with HDPCs, cell proliferation experiment （EdU） was used to detect the relative activity of induced HDPCs. Real-time qPCR was used to detect the expression level of alkaline phosphatase （ALP）, and Western blot was used to detect β-catenin, Wnt10b, GSK-3β expression at the protein level. Results The obtained primary HDPCs, hUC-MSCs, and hUCMSC-Exos were all conformed to the characteristics of dermal papilla cells, mesenchymal stem cells, and exosomes. The number of EdU positive cells significantly increased, and exosomes could effectively promote the proliferation of HDPCs （P < 0.05）, enhance the vitality of HDPCs and alleviate the damage caused by DHT（P < 0.05）. Real-time qPCR showed that exosomes could enhance the expression level of ALP gene （P < 0.05） and hair follicle induction ability. Western Blot confirmation β-catenin, Wnt10b, GSK-3β were differences in expression at the protein level （P < 0.05）. Conclusions HUCMSC-Exos could promote DHT induced proliferation of HDPCs, enhance their hair follicle regeneration and repair ability, and its mechanism may be related to the activation of Wnt/β-catenin signaling pathway. [ABSTRACT FROM AUTHOR]

Background: The homologous proteins identified as cellular retinoic acid-binding proteins I and II (CRABP-I and CRABP-II) belong to a subset of intracellular proteins characterized by their robust affinity for retinoic acid, which plays an indispensable role in the development of hair follicle, including differentiation, proliferation, and apoptosis in keratinocytes. Previous research on Hu sheep hair follicles revealed the specific expression CRABP1 in dermal papilla cells (DPCs), suggesting that CRABP1 has a potential role in regulating the DPC population. Therefore, the main purpose of this study is to expose the performance of the CRABP1 genes in the development and proliferation of DPCs. Methods: Initially, overexpression and inhibition of CRABP1 in the DPCs were conducted through overexpression vector and siRNA. CCK-8, EDU, and RT-PCR cell cycle assays and immunostaining were performed to evaluate the proliferation and cell cycle of dermal papilla cells (DPCs). Although, the influence of CRABP1 upon β-catenin in dermal papilla cells (DPCs) was found using immunofluorescence labeling. Finally, RT-PCR was conducted to assess the impact of CRABP1 on the expression levels of CTNNB1, TCF4, and LEF1 in DPCs involved in the Wnt/βcatenin signaling pathway. Results: The results showed that CRABP1 overexpression promotes the growth rates of DPCs and significantly enhances the proportion of S-phase cells compared with the control group (p < 0.05). The results were the opposite when CRABP1 was a knockdown. In contrast, there was a significant decline in the mRNA expression levels of CTNNβ1, LEF1 (p < 0.05), and TCF4 (p < 0.01) by CRABP1 knockdown. Conclusions: This study found that CRABP1 influences the expression of important genes within the Wnt/β-catenin signaling pathway and promotes DPC proliferation. This investigation provides a theoretical framework to explain the mechanisms that control hair follicle morphogenesis and development. [ABSTRACT FROM AUTHOR]

With the escalating prevalence of hair loss, the demand for effective hair loss treatment has surged. This study evaluated the effects of hot water extract of Hydrangea serrata (Thunb.) Ser. leaf (WHS) on hair growth, employing cell cultures, mice, and human skin organoid models. Both WHS and hydrangenol were found to enhance 5α-reductase inhibitory activity. WHS and hydrangenol have been shown to stimulate dermal papilla cell (DPC) growth, potentially through factors like keratinocyte growth factor (KGF), fibroblast growth factor 10 (FGF10), and transforming growth factor-β1 (TGF-β1). They also elevated the expression levels of keratin genes (K31 and K85) and the ceramide synthase (CerS3) gene, crucial clinical indicators of hair health. Furthermore, they exhibited notable anti-inflammatory and anti-androgenic properties by reducing the levels of tumor necrosis factor-α (TNF-α) and androgen signaling molecules, including androgen receptor (AR) and dickkopf-1 (DKK-1) gene expression. Oral administration of WHS to C57BL/6 mice for 3 weeks confirmed its hair growth-promoting effects, improving hair growth parameters and gene expression without significant changes in hair weight. Additionally, in a human skin organoid model, WHS was found to stimulate hair formation and augment the expression of follicle markers. These findings position WHS as a promising nutraceutical for promoting hair health, as evidenced by its efficacy in both in vitro and in vivo models. [ABSTRACT FROM AUTHOR]

Botulinum toxin type A (BTXA) has the potential to treat androgenetic alopecia (AGA); however, its impact on the apoptosis of dermal papillary cells (DPCs) is not yet fully understood. Noncoding RNAs play a crucial role in AGA. In this study, we investigated the potential mechanism by which BTXA alleviates apoptosis induced by dihydrotestosterone (DHT) in DPCs. We assessed the mRNA levels of circ_0135062, miR-506-3p, and Bax using qRT–PCR. Binding interactions were analyzed using RNA pulldown and dual-luciferase assays. Cell viability was determined using a cell counting kit-8 assay, and cell apoptosis was assessed using flow cytometry, TUNEL assays, and western blotting. Our findings revealed that BTXA inhibited the apoptosis of DPCs treated with DHT. Moreover, circ_0135062 overexpression counteracted the protective effect of BTXA on DHT-treated DPCs. MiR-506-3p was found to interact with Bax and inhibit apoptosis in DPCs by suppressing Bax expression in response to DHT-induced damage. Furthermore, circ_0135062 acted as a sponge for miR-506-3p, thereby inhibiting the targeting of Bax expression by miR-506-3p. In conclusion, BTXA exhibited an antiapoptotic effect on DHT-induced DPC injury via the circ_0135062/miR-506-3p/Bax axis. Level of Evidence II This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266. [ABSTRACT FROM AUTHOR]

Abstract Piperine, an alkaloid compound in black pepper (Piper nigrum), has beneficial bioactivities. Specifically, piperine inhibits adipogenesis in 3T3-L1 cells by suppressing the transcriptional activity of PPARγ. Control of hair oiliness, which is related to adipogenic regulation, is important to prevent hair loss. Excessive sebum from the sebaceous gland (SG) can cause acne, folliculitis, or irritated skin by clogging pores. To investigate the in vivo function of piperine in SG, we used mice fed a high-fat diet (HFD). The HFD increased the size and Oil Red O (ORO) staining intensity of SG, which were significantly reduced by piperine. The HFD also upregulated the expression of sebocyte-associated genes, including PPARγ target genes, an effect reversed by piperine. In CD34/CD49f double-positive hair follicle bulge stem cells isolated from mouse vibrissae, piperine inhibited cellular adipogenesis, likely via transcriptional repression of related genes. Furthermore, piperine reduced the thickness of subcutaneous fat. In human dermal papilla cells, piperine inhibited cellular adipogenesis, as shown by the reduction in ORO staining and the downregulation of PPARγ target genes. In conclusion, piperine can be used to reduce hair greasiness by suppressing adipogenesis in hair stem cells.

Traidit Thianthanyakij,1,2,&ast; Yinghui Zhou,1,&ast; Mengyi Wu,3,&ast; Yuting Zhang,4 Jui-Ming Lin,1 Yan Huang,4 Yuou Sha,1 Jiayi Wang,1 Sirapath Peter Kong,2 Jinran Lin,1 Qingmei Liu,1 Wenyu Wu1,5,6 1Department of Dermatology, Huashan Hospital, Fudan University, Shanghai Institute of Dermatology, Shanghai, 200040, People’s Republic of China; 2Faculty of Medicine, Thammasat University (Rangsit Campus), Pathumthani, 12120, Thailand; 3Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, People’s Republic of China; 4State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, Shanghai, 200433, People’s Republic of China; 5Department of Dermatology, Jing’an District Central Hospital, Shanghai, 200040, People’s Republic of China; 6Academy for Engineering and Technology, Fudan University, Shanghai, 200433, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qingmei Liu; Wenyu Wu, Email liuqing.mei@163.com; wenyu_wu@fudan.edu.cnBackground: Existing research links oxidative stress and inflammation to hair loss. Salvianolic acid B (SAB) is known for its anti-oxidative, anti-inflammatory, and other beneficial pharmacological properties.Objective: To assess the efficacy of SAB in modulating hair growth.Methods: In vivo experiments were conducted using C57BL/6 mice to evaluate the effects of SAB on hair and skin parameters. The study involved ex vivo analysis of human hair follicles (HFs) for hair shaft length and hair growth cycle assessment. In vitro, human dermal papilla cells (hDPCs) were cultured with SAB, and their proliferation, protection against H2O2-induced oxidative damage, and gene/protein expression alterations were examined using various analytical techniques, including Real-Time Cell Analysis (RTCA), DCFH-DA Assay, RNA-seq, and KEGG pathway analysis.Results: SAB treatment in mice significantly improved hair growth and vascularization by day 21. In human HFs, SAB extended hair shaft length and delayed the transition to the catagen phase. SAB-treated hDPCs showed a notable decrease in the expression of oxidation-antioxidation-related genes and proteins, including reduced phosphorylation levels of ERK and p38.Conclusion: The study indicates that SAB promotes hDPC proliferation and offers protection against oxidative stress, highlighting its potential as a therapeutic agent for enhancing hair growth and treating hair loss.Keywords: salvianolic acid B, hair growth, hair cycle, hair follicle, dermal papilla cells

Hair is an essential protective and health-maintaining covering for the body, especially the scalp. It is also important esthetically in modern society, where hair loss, whether caused by the severe scalp condition androgenic alopecia or other internal or external factors, has societal and psychological impacts. Preventing the apoptosis of human hair follicle cells, including hair follicle dermal papilla cells (HFDPCs) and human hair follicle keratinocytes (HHFKs), is crucial for hair production, alongside hair strengthening, which is essential in combatting hair loss. Given the structural importance of collagen peptides in the skin matrix and tissues surrounding hair follicles, we studied the function of AP collagen peptides (APCP) as a hair growth and quality improvement agent. APCP was found to stimulate the proliferation of hair follicle cells and counteract H2O2-induced apoptosis. It also significantly suppressed the expression of dickkopf-1 (DKK1) and bone morphogenetic protein 6 (BMP6), which induce hair cell apoptosis in the presence or absence of UVA/B irradiation. Moreover, APCP induced expression of the antioxidant enzymes, catalase and superoxide dismutase 1 (SOD1), while enhancing hair keratin expression in HHFKs. Mechanistically, APCP facilitated hair growth by elevating GAS6 expression and activating PKA and AKT/ERK signaling pathways. Notably, APCP increased levels of phosphor-β-catenin (Ser552/Ser675) as well as total β-catenin, as demonstrated by Western blotting and immunocytochemistry. Lastly, we showed that APCP increased expression of the hair cuticle type I keratins, keratin-32 and 42, in HHFKs. Overall, these findings propose APCP as a promising candidate for safeguarding hair follicle cells and mitigating hair loss by improving hair growth and quality. [ABSTRACT FROM AUTHOR]

Piperine, an alkaloid compound in black pepper (Piper nigrum), has beneficial bioactivities. Specifically, piperine inhibits adipogenesis in 3T3-L1 cells by suppressing the transcriptional activity of PPARγ. Control of hair oiliness, which is related to adipogenic regulation, is important to prevent hair loss. Excessive sebum from the sebaceous gland (SG) can cause acne, folliculitis, or irritated skin by clogging pores. To investigate the in vivo function of piperine in SG, we used mice fed a high-fat diet (HFD). The HFD increased the size and Oil Red O (ORO) staining intensity of SG, which were significantly reduced by piperine. The HFD also upregulated the expression of sebocyte-associated genes, including PPARγ target genes, an effect reversed by piperine. In CD34/CD49f double-positive hair follicle bulge stem cells isolated from mouse vibrissae, piperine inhibited cellular adipogenesis, likely via transcriptional repression of related genes. Furthermore, piperine reduced the thickness of subcutaneous fat. In human dermal papilla cells, piperine inhibited cellular adipogenesis, as shown by the reduction in ORO staining and the downregulation of PPARγ target genes. In conclusion, piperine can be used to reduce hair greasiness by suppressing adipogenesis in hair stem cells. [ABSTRACT FROM AUTHOR]

Background/Aim: Particular matter 2.5 (PM2.5) pollution is associated with senescence induction. Since the impact of PM2.5 on stem cell senescence and potential compounds capable of reversing this process are largely unknown, this study aimed to examine the senescence effects of PM2.5 on dermal papilla (DP) stem cells. Additionally, we explored the reversal of these effects using natural product-derived substances, such as resveratrol (Res) or Emblica fruits, soybean, and Thunbergia Laurifolia (EST) extract. Materials and Methods: Cell senescence was determined using the ß-Galactosidase (SA-ß-gal) assay. The senescence-associated secretory phenotype (SASP) was detected using real-time RT-PCR. For senescence markers, the mRNA and protein levels of p21 and p16 were measured using real-time RT-PCR and immunofluorescence analysis. Results: Subtoxic concentration of PM2.5 (50 µg/ml) induced senescence in DP cells. Resveratrol (50, 100 µM) and plant extracts (400, 800 µg/ml) reversed PM2.5-induced cell senescence. Treatment with Res or EST significantly decreased SA-ß-gal staining in PM2.5-treated cells. Furthermore, Res and EST decreased the mRNA levels of SASP, including IL1a, IL7, IL8, and CXCL1. DP cells exposed to PM2.5 exhibited an increase in p21 and p16 mRNA and protein levels, which could be reversed by the addition of Res or EST. Res and EST could reduce p21 and p16 in senescent cells approximately 3- and 2-fold, respectively, compared to untreated senescent cells. Conclusion: PM2.5 induced senescence in human DP stem cells. Res and EST extract potentially reverse the senescence phenotypes of such cells. [ABSTRACT FROM AUTHOR]

Background: Deer placenta extract (DPE), rich in bioactive macromolecules, promotes regenerative effects in both normal and damaged cells. However, effective delivery of these macromolecules through the skin remains a challenge. Objectives: To investigate the potential of DPE in regenerating hair cells and to develop a nanoniosome (NS) and microspicule (MS) formulation as a promising transfollicular delivery system. Methods: The bioactivity of DPE was assessed in human follicle dermal papilla (HFDP) cells, including cells damaged by chemotherapy. The NS-MS formulation was designed to deliver biomacromolecules from DPE into skin and hair follicles. Results: DPE at 2000 µg/mL exhibited no cytotoxicity and significantly enhanced proliferation in both normal and cisplatin-treated HFDP cells. The DPE-loaded NSs displayed nanovesicles with a uniform size distribution and a negative surface charge. When incorporated into the MS gel, NS-MS demonstrated a synergistic effect, significantly enhancing the transdermal and transfollicular delivery of macromolecular protein into the skin layers and hair follicles. Conclusions: DPE promoted hair cell proliferation and facilitated the recovery of hair cells damaged by chemotherapy, especially when formulated into the NS-MS system, which effectively delivered bioactive macromolecules to the target site. This suggests its potential role in promoting hair regrowth.

Dermal papilla cells (DPCs) regulate the hair cycle and play important roles in hair growth and regeneration. Alopecia is a pathology caused by a deregulation in the hair cycle phases. Currently, the use of physical therapies such as radiofrequency (RF) as an alternative to pharmacological treatment is increasing. Electrical stimulation by capacitive resistive electrical transfer (CRET) is one of these therapies. The objective of the present study was to analyze the effect of RF-CRET currents on DPCs. Cells were treated with subthermal 448 kHz CRET currents with two different types of signals: standard (CRET-STD) or modulated (CRET-MOD). Viability (XTT Assay), proliferation (Ki67 and ERK1/2), apoptosis (p53 and caspase 3), differentiation (β-catenin and α-SMA), and anagen markers (versican and PPARγ) were analyzed by immunofluorescence and immunoblot. CRET caused effects on the proliferation and survival of DPCs associated with increases in the expression of p-MAPK-ERK1/2, cyclin D1, and decreases in the expression of p53 and caspase 3. Also, CRET caused significant transient increases in the expression of β-catenin, involved in hair growth, and in the expression of anagen phase markers such as versican and PPARγ related to hair follicle maintenance. The present study highlights the ability of treatment with CRET therapy to cause molecular alterations in DPC involved in hair regeneration.

Suaeda glauca, a halophyte in the Amaranthaceae family, exhibits remarkable resilience to high salt and alkali stresses despite the absence of salt glands or vesicles in its leaves. While there is growing pharmacological interest in S. glauca, research on its secondary metabolites remains limited. In this study, chemical constituents of the aerial parts of S. glauca were identified using 1D- and 2D-NMR experiments, and its biological activity concerning hair loss was newly reported. Eight compounds, including alkaloids (1~3), flavonoids (4~6), and phenolics (7 and 8), were isolated. The compounds, except the flavonoids, were isolated for the first time from S. glauca. In the HPLC chromatogram, quercetin-3-O-β-d-glucoside, kaempferol-3-O-β-d-glucoside, and kaempferol were identified as major constituents in the extract of S. glauca. Additionally, the therapeutic potential of the extract of S. glauca and the isolated compounds 1~8 on the expressions of VEGF and IGF-1, as well as the regulation of Wnt/β-catenin signaling, were evaluated in human follicle dermal papilla cells (HFDPCs) and human umbilical vein endothelial cells (HUVECs). Among the eight compounds, compound 4 was the most potent in terms of increasing the expression of VEGF and IGF-1 and the regulation of Wnt/β-catenin. These findings suggest that S. glauca extract and its compounds are potential new candidates for preventing or treating hair loss. [ABSTRACT FROM AUTHOR]

Alopecia is a prevalent problem of cutaneous appendages and lacks effective therapy. Recently, researchers have been focusing on mesenchymal components of the hair follicle, i.e. dermal papilla cells, and we previously identified biglycan secreted by dermal papilla cells as the key factor responsible for hair follicle‐inducing ability. In this research, we hypothesized biglycan played an important role in hair follicle cycle and regeneration through regulating the Wnt signalling pathway. To characterize the hair follicle cycle and the expression pattern of biglycan, we observed hair follicle morphology in C57BL/6 mice on Days 0, 3, 5, 12 and 18 post‐depilation and found that biglycan is highly expressed at both mRNA and protein levels throughout anagen in HFs. To explore the role of biglycan during the phase transit process and regeneration, local injections were administered in C57BL/6 and nude mice. Results showed that local injection of biglycan in anagen HFs delayed catagen progression and involve activating the Wnt/β‐catenin signalling pathway. Furthermore, local injection of biglycan induced HF regeneration and up‐regulated expression of key Wnt factors in nude mice. In addition, cell analyses exhibited biglycan knockdown inactivated the Wnt signalling pathway in early‐passage dermal papilla cell, whereas biglycan overexpression or incubation activated the Wnt signalling pathway in late‐passage dermal papilla cells. These results indicate that biglycan plays a critical role in regulating HF cycle transit and regeneration in a paracrine and autocrine fashion by activating the Wnt/β‐catenin signalling pathway and could be a potential treatment target for hair loss diseases. [ABSTRACT FROM AUTHOR]

Dermal papilla cells (DPCs) undergo premature ageing in androgenetic alopecia and senescent alopecia. As critical components of hair follicle reconstruction, DPCs are also prone to senescence in vitro, resulting in a diminished hair follicle inductivity capacity. Dermal sheath cup cells (DSCCs), a specific subset of hair follicle mesenchymal stem cells, intimately linked to the function of DPCs. The primary objective of this research is to investigate the anti‐ageing effect of exosomes derived from DSCCs (ExoDSCCs) on DPCs. Exosomes were utilized to treat H2O2‐induced DPCs or long‐generation DPCs(P10). Our findings demonstrate that ExoDSCCs(P3) promote the proliferation, viability and migration of senescent DPCs while inhibiting cell apoptosis. The expression of senescence marker SA‐β‐Gal were significantly downregulated in senescent DPCs. When treated with ExoDSCCs(P3), expression of inducibility related markers alkaline phosphatase and Versican were significantly upregulated. Additionally, ExoDSCCs(P3) activated the Wnt/β‐catenin signalling in vitro. In patch assay, ExoDSCCs(P3) significantly promoted hair follicle reconstruction in senescent DPCs. In summary, our work highlights that ExoDSCCs(P3) may restore the biological functions and improve the hair follicle induction ability of senescent DPCs. Therefore, ExoDSCCs(P3) may represent a new strategy for intervening in the ageing process of DPCs, contributing to the prevention of senile alopecia. [ABSTRACT FROM AUTHOR]

Exosomes are lipid bilayer vesicles, 30–200 nm in diameter, that are produced by cells and play essential roles in cell–cell communication. Exosomes have been studied in several medical fields including dermatology. Hair loss, a major disorder that affects people and sometimes causes mental stress, urgently requires more effective treatment. Because the growth and cycling of hair follicles are governed by interactions between hair follicle stem cells (HFSCs) and dermal papilla cells (DPCs), a better understanding of the mechanisms responsible for hair growth and cycling through exosomes may provide new insights into novel treatments for hair loss. In this review, we focused on the comprehensive knowledge and recent studies on exosomes in the field of hair development and regeneration. We classified exosomes of several cellular origins for the treatment of hair loss. Exosomes and their components, such as microRNAs, are promising drugs for effective hair loss treatment. [ABSTRACT FROM AUTHOR]

Previous studies have shown that melatonin has a certain regulatory effect on the growth of sheep wool. However, the mechanism of melatonin action remains unknown. In the present study, we aimed to understand the role of exogenous melatonin in the dermal papilla cells of Hu sheep. To confirm the optimal melatonin treatment regimen for Hu sheep dermal papilla cells, we detected the cell viability by exposing them to different concentrations of melatonin and different treatment times. The results showed that cell viability was best when dermal papilla cells were treated with 1000 pg/ml of melatonin for 48 h. According to the results of qPCR, CCK-8, EDU, Western blot, and Flow cytometry analysis, we found that 1000 pg/ml melatonin promoted the proliferation and inhibited the apoptosis of dermal papilla cells compared with the exogenous melatonin blank group (control group). Furthermore, we also found that 1000 pg/ml of melatonin promoted the cell cycle progress of dermal papilla cells according to the results of qPCR and Flow cytometry analysis. Overall, our findings showed that melatonin plays an important role in the dermal papilla cells of Hu sheep. [ABSTRACT FROM AUTHOR]

Dermal papilla cells (DPCs) are the key dermal component of the hair follicle that directly regulates hair follicle development, growth and regeneration. Successfully isolated and cultured DPCs from Small-tail Han sheep could provide a good model for the study of hair follicle development mechanism in vitro. DPCs were isolated using enzyme digestion and dissecting microscope from Small-tail Han sheep. Adherent cells were identified by cell characteristics, particular gene expression, differentiation capability to adipocyte and osteoblast using specific differentiation mediums. Additionally, flow cytometry was used to detect the cell cycle of DPCs. Cells originating from the dermal papilla showed the morphological appearance of mesenchymal cells (fibroblast-like cells). Purified DPCs were positive for α-SMA (α smooth muscle actin) and vimentin; in addition to their strong proliferation abilities in vitro, these DPCs can be differentiated into adipocyte and osteoblasts lineage under appropriate culture condition. DPCs were successfully isolated and subcultured from Small-tail Han sheep, which exhibited progenitor cell features and multiple differentiation potency. It provides a material for studying the molecular mechanism of hair follicle development and hair cycle, which will promote wool production in the future. [ABSTRACT FROM AUTHOR]

Background: Androgenetic alopecia (AGA) is the most common cause of chronic progressive hair loss in men, and AGA has a severe negative impact on the quality of life and physical and mental health of patients. Methods: Four female C57BL/6 mice were isolated from DP cells in culture (≤4 generations) after stimulation of DPC proliferation by herbal concentrations obtained by the CCK‐8 method, and exosomes were isolated by differential centrifugation at low temperature. Testosterone propionate and topical hair removal treatments were used together to establish the C57BL/6 mouse AGA model, which was treated with LTF, 5% minoxidil, and LTF‐DPC‐EXO, respectively. ELISA was used to detect serum hormone levels, in vivo tracing was used to observe dynamic changes in exosomes, H&E staining showed changes in mouse hair follicle tissue, and (q) RT‐PCR and WB were used to detect dorsal skin VEGF, AKT1, and CASP3 expression in dorsal skin tissues. Results: Hair regeneration was significant in the LTF group, minoxidil group, and LTF‐DPC‐EXO group mice, and the hair growth was only seen in the local skin in the model group. The hormone T in all treatment groups was lower than that in the model group, and e2 was higher than that in the model group. (q) RT‐PCR and western blot showed that VEGF and AKT1 expressions were upregulated and Caspase3 expression was downregulated in the skin sections of mice in the treatment groups. Conclusion: DPC‐EXO obtained through LTF may activate AKT1 and VEGF in the PI3K/AKT signaling pathway to inhibit CASP3, thereby protecting DPC to restore the hair growth. [ABSTRACT FROM AUTHOR]

Alopecia is a common and distressing medical condition that has affected a majority of people worldwide, which leads to great effects on the quality of life and self-esteem. Numerous treatments had been used to cure alopecia, including hair growth stimulants, herbal products, and hair transplantation. However, these treatments have their side effects, such as hypertrichosis, edema, and even cardiovascular adverse effects, which lead to the urgent requirement to explore a new hair-follicle (HF) regeneration approach. Tissue engineering could be the potential way for HF regeneration by simulating the epithelial-mesenchymal interaction and cell-extracellular matrix interactions. This review summarized the potential cells that are used in tissue engineering, commonly used tissue engineering techniques, and most importantly, the biomaterials that have been applied for in vitro three-dimensional cell culture or in vivo co-transplantation in HF regeneration. The literature shows that advances in this field toward functional HF development have progressively increased. Although the clinical application of biomaterial co-transplantation for HF regeneration still faces various challenges, numerous studies have proved that this is a promising direction that could be achieved in the future.

To adapt to the extreme conditions of plateau environments, yaks have evolved thick hair, making them an ideal model for investigating the mechanisms involved in hair growth. We can gain valuable insights into how hair follicles develop and their cyclic growth in challenging environments by studying yaks. However, the lack of essential data on yak hair follicle histology and the absence of in vitro cell models for hair follicles serve as a limitation to such research objectives. In this study, we investigated the structure of skin tissue during different hair follicle cycles using the yak model. Additionally, we successfully established in vitro models of hair follicle-associated cells derived from yak skin, including dermal papilla cells (DPCs), preadipocytes, and fibroblasts. We optimized the microdissection technique for DPCs culture by simplifying the procedure and reducing the time required. Furthermore, we improved the methodology used to differentiate yak preadipocytes into mature adipocytes, thus increasing the differentiation efficiency. The introduction of yak as a natural model provides valuable research resources for exploring the mechanisms of hair growth and contributes to a deeper understanding of hair follicle biology and the development of regenerative medicine strategies.

Stem cells have demonstrated significant potential for tissue engineering and repair, anti-aging, and rejuvenation. Hair follicle stem cells can be found in the dermal papilla at the base of the follicle and the bulge region, and they have garnered increased attention because of their potential to regenerate hair as well as their application for tissue repair. In recent years, these cells have been shown to affect hair restoration and prevent hair loss. These stem cells are endowed with mesenchymal characteristics and exhibit self-renewal and can differentiate into diverse cell types. As research in this field continues, it is probable that insights regarding stem cell maintenance, as well as their self-renewal and differentiation abilities, will benefit the application of these cells. In addition, an in-depth discussion is required regarding the molecular basis of cellular signaling and the influence of nature-derived compounds in stimulating the stemness properties of dermal papilla stem cells. This review summarizes (i) the potential of the mesenchymal cells component of the hair follicle as a target for drug action; (ii) the molecular mechanism of dermal papilla stem cells for maintenance of their stem cell function; and (iii) the positive effects of the natural product compounds in stimulating stemness in dermal papilla stem cells. Together, these insights may help facilitate the development of novel effective hair loss prevention and treatment. [ABSTRACT FROM AUTHOR]

Dermal papilla cells (DPCs) cultured in vitro induce hair follicle formation. Using a hypoxic microenvironment to culture adipose mesenchymal stem cells (ADSCs) can promote hair follicle growth. However, the exact molecular mechanisms underlying this process remain unclear. In this study, ADSCs and DPCs from Arbas Cashmere goats were used. A hypoxic microenvironment promoted the proliferation of ADSCs and increased the pluripotency of ADSCs. The growth factors vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and platelet-derived growth factor (PDGF) were upregulated in ADSCs in the hypoxia-conditioned medium (Hypo-cm). Hypo-cm also enhanced the ability of DPCs to induce hair follicle formation. Inhibitors of the ERK1/2 signaling pathway caused the expressions of growth factors that increased in hypoxic microenvironments to decrease; moreover, hypoxia-inducible factor-1α (HIF-1α) increased the expression levels of VEGF, bFGF, and PDGF and inhibited the expression of bone morphogenic protein 7 (BMP7). In conclusion, these findings improve the theoretical basis for the development of gene therapy drugs for the treatment of alopecia areata and hair thinning. [ABSTRACT FROM AUTHOR]

Alopecia has gradually become a problem that puzzles an increasing number of people. Dermal papilla cells (DPCs) play an important role in hair follicle (HF) growth; thus, exploring the effective chemicals or natural extracts that can remediate the growth of DPCs is vital. Our results showed that Schizochytrium sp.-extracted lipids (SEL) significantly promoted proliferation (up to 1.13 times) and survival ratio (up to 2.45 times) under oxidative stress. The treatment with SEL can protect DPCs against oxidative stress damage, reducing the reactive oxygen species (ROS) level by 90.7%. The relative gene transcription and translation were thoroughly analyzed using RNA-Seq, RT-qPCR, and Western blot to explore the mechanism. Results showed that SEL significantly inhibited the ferroptosis pathway and promoted the expression of antioxidant genes (up to 1.55–3.52 times). The in vivo application of SEL improved hair growth, with the length of new hair increasing by 16.7% and the length of new HF increasing by 92.6%, and the period of telogen shortening increased by 40.0%. This study proposes a novel therapeutic option for alopecia, with the effect and regulation mechanism of SEL on DPC systematically clarified. [ABSTRACT FROM AUTHOR]

Hair fiber growth is determined by the spatiotemporally controlled proliferation, differentiation, and apoptosis of hair matrix cells (HMCs) inside the hair follicle (HF); however, dermal papilla cells (DPCs), the cell population surrounded by HMCs, manipulate the above processes via intercellular crosstalk with HMCs. Therefore, exploring how the mutual commutations between the cells are molecularly achieved is vital to understanding the mechanisms underlying hair growth. Here, based on our previous successes in cultivating HMCs and DPCs from cashmere goats, we combined a series of techniques, including in vitro cell coculture, transcriptome sequencing, and bioinformatic analysis, to uncover ligand-receptor pairs and signaling networks mediating intercellular crosstalk. Firstly, we found that direct cellular interaction significantly alters cell cycle distribution patterns and changes the gene expression profiles of both cells at the global level. Next, we constructed the networks of ligand-receptor pairs mediating intercellular autocrine or paracrine crosstalk between the cells. A few pairs, such as LEP-LEPR, IL6-EGFR, RSPO1-LRP6, and ADM-CALCRL, are found to have known or potential roles in hair growth by acting as bridges linking cells. Further, we inferred the signaling axis connecting the cells from transcriptomic data with the advantage of CCCExplorer. Certain pathways, including INHBA-ACVR2A/ACVR2B-ACVR1/ACVR1B-SMAD3, were predicted as the axis mediating the promotive effect of INHBA on hair growth via paracrine crosstalk between DPCs and HMCs. Finally, we verified that LEP-LEPR and IL1A-IL1R1 are pivotal ligand-receptor pairs involved in autocrine and paracrine communication of DPCs and HMCs to DPCs, respectively. Our study provides a comprehensive landscape of intercellular crosstalk between key cell types inside HF at the molecular level, which is helpful for an in-depth understanding of the mechanisms related to hair growth. [ABSTRACT FROM AUTHOR]

Cacumen Platycladi (CP) consists of the dried needles of Platycladus orientalis L.) Franco. It was clinically demonstrated that it effectively regenerates hair, but the underlying mechanism remains unknown. Thus, we employed shaved mice to verify the hair growth-promoting capability of the water extract of Cacumen Platycladi (WECP). The morphological and histological analyses revealed that WECP application could significantly promote hair growth and hair follicles (HFs) construction, in comparison to that of control group. Additionally, the skin thickness and hair bulb diameter were significantly increased by the application of WECP in a dose-dependent manner. Besides, the high dose of WECP also showed an effect similar to that of finasteride. In an in vitro assay, WECP stimulated dermal papilla cells (DPCs) proliferation and migration. Moreover, the upregulation of cyclins (cyclin D1, cyclin-dependent kinase 2 (CDK2), and cyclindependent kinase 4 (CDK4)) and downregulation of P21 in WECP-treated cell assays have been evaluated. We identified the ingredients of WECP using ultrahigh-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q/TOF-MS) and endeavored to predict their relevant molecular mechanisms by network analysis. We found that the Akt (serine/threonine protein kinase) signaling pathway might be a crucial target of WECP. It has been demonstrated that WECP treatment activated the phosphorylation of Akt and glycogen synthase kinase-3-beta (GSK3β), promoted β-Catenin and Wnt10b accumulation, and upregulated the expression of lymphoid enhancerbinding factor 1 (LEF1), vascular endothelial growth factor (VEGF), and insulin-like growth factor 1 (IGF1). We also found that WECP significantly altered the expression levels of apoptosis-related genes in mouse dorsal skin. The enhancement capability of WECP on DPCs proliferation and migration could be abrogated by the Akt-specific inhibitor MK-2206 2HCl. These results suggested that WECP might promote hair growth by modulating DPCs proliferation and migration through the regulation of the Akt/GSK3β/β-Catenin signaling pathway. [ABSTRACT FROM AUTHOR]

The skin is the largest organ of the human body, composed of a diverse range of cell types, non-cellular components, and an extracellular matrix. With aging, molecules that are part of the extracellular matrix undergo qualitative and quantitative changes and the effects, such as a loss of skin firmness or wrinkles, can be visible. The changes caused by the aging process do not only affect the surface of the skin, but also extend to skin appendages such as hair follicles. In the present study, the ability of marine-derived saccharides, L-fucose and chondroitin sulphate disaccharide, to support skin and hair health and minimize the effects of intrinsic and extrinsic aging was investigated. The potential of the tested samples to prevent adverse changes in the skin and hair through stimulation of natural processes, cellular proliferation, and production of extracellular matrix components collagen, elastin, or glycosaminoglycans was investigated. The tested compounds, L-fucose and chondroitin sulphate disaccharide, supported skin and hair health, especially in terms of anti-aging effects. The obtained results indicate that both ingredients support and promote the proliferation of dermal fibroblasts and dermal papilla cells, provide cells with a supply of sulphated disaccharide GAG building blocks, increase ECM molecule production (collagen and elastin) by HDFa, and support the growth phase of the hair cycle (anagen). [ABSTRACT FROM AUTHOR]

Heat stress (HS) negatively affects the development of hair follicles. The present study investigated the effect of vitamin A (VA) on the development of rabbit dermal papilla cells (DPCs) under HS and the underlying regulatory mechanisms. Addition of 0.4 mg/L VA to the culture medium significantly enhanced cell proliferation (P

Abstract Background Tissue engineering of hair follicles (HFs) has enormous potential for hair loss treatment. However, certain challenges remain, including weakening of the dermal papilla cell (DPC) viability, proliferation, and HF inducibility, as well as the associated inefficient and tedious preparation process required to generate extracellular matrix (ECM)-mimicking substrates for biomolecules or cells. Herein, we utilized gelatin methacryloyl (GelMA) and chitosan hydrogels to prepare scalable, monodispersed, and diameter-controllable interpenetrating network GelMA/chitosan-microcarriers (IGMs) loaded with platelet-rich plasma (PRP) and seeded with DPCs, on a high-throughput microfluidic chip. Results The ECM-mimicking hydrogels used for IGMs exhibited surface nano-topography and high porosity. Mass production of IGMs with distinct and precise diameters was achieved by adjusting the oil and aqueous phase flow rate ratio. Moreover, IGMs exhibited appropriate swelling and sustained growth factor release to facilitate a relatively long hair growth phase. DPCs seeded on PRP-loaded IGMs exhibited good viability (> 90%), adhesion, spreading, and proliferative properties (1.2-fold greater than control group). Importantly, PRP-loaded IGMs presented a higher hair inducibility of DPCs in vitro compared to the control and IGMs group (p

Hair follicle mesenchymal stem cells (HFMSCs) are slow cycling label retaining cells with self-regeneration ability, high proliferative potential, and multi-directional differentiation. HFMSCs can induce and promote the regeneration of the epidermis, hair follicles and sebaceous glands. HFMSCs have important advantages in regenerative medicine because of their abundance, wide availability, expansion in vitro, no genetic manipulation, no tumor formation and no ethical restriction. The synergy and antagonism between Wnt and other signaling pathways such as Shh, Notch and BMP signaling pathways play a crucial role in the regulation of stem cell homeostasis, epidermal development and hair follicle regeneration. The dysregulation of these pathways may result in hair loss diseases or skin tumors. This paper summarizes the classification and some specific biomarkers of HFMSCs, and discusses the induction of HFMSCs and the biomolecular pathways that affect hair regeneration, so as to shed light on the treatment strategies of hair diseases.

Alopecia, regardless of gender, exacerbates psychological stress in those affected. The rising prevalence of alopecia has fueled a research interest in preventing hair loss. This study investigates the potential of millet seed oil (MSO) in promoting the proliferation of hair follicle dermal papilla cells (HFDPC) and stimulating hair growth in animals with testosterone-dependent hair growth inhibition as part of a study on dietary treatments to improve hair growth. MSO-treated HFDPC significantly increased cell proliferation and phosphorylation of AKT, S6K1, and GSK3ß proteins. This induces ß-catenin, a downstream transcription factor, to translocate to the nucleus and increase the expression of factors related to cell growth. In a C57BL/6 mice model in which hair growth was inhibited by subcutaneous testosterone injection after shaving the dorsal skin, oral administration of MSO stimulated hair growth in the subject mice by increasing the size and number of hair follicles. These results suggest that MSO is a potent agent that may help prevent or treat androgenetic alopecia by promoting hair growth. [ABSTRACT FROM AUTHOR]

Fibroblast growth factor 9 (FGF9) is crucial for the growth and development of hair follicles (HFs); however, its role in sheep wool growth is unknown. Here, we clarified the role of FGF9 in HF growth in the small-tailed Han sheep by quantifying FGF9 expression in skin tissue sections collected at different periods. Moreover, we evaluated the effects of FGF9 protein supplementation on hair shaft growth in vitro and FGF9 knockdown on cultured dermal papilla cells (DPCs). The relationship between FGF9 and the Wnt/β-catenin signaling pathway was examined, and the underlying mechanisms of FGF9-mediated DPC proliferation were investigated. The results show that FGF9 expression varies throughout the HF cycle and participates in wool growth. The proliferation rate and cell cycle of FGF9-treated DPCs substantially increase compared to that of the control group, and the mRNA and protein expression of CTNNB1, a Wnt/β-catenin signaling pathway marker gene, is considerably lower than that in the control group. The opposite occurs in FGF9-knockdown DPCs. Moreover, other signaling pathways are enriched in the FGF9-treated group. In conclusion, FGF9 accelerates the proliferation and cell cycle of DPCs and may regulate HF growth and development through the Wnt/β-catenin signaling pathway. [ABSTRACT FROM AUTHOR]

Objective: Hair loss is caused by various factors. Impacts of these factors are often overlapped and intensified. Currently, mitigation of hair loss is being studied by proliferating dermal papilla cells (DPCs) and inhibiting deleterious factors such as dihydrotestosterone (DHT) and oxidative stress on hair growth. Camellia japonica (C. japonica) fruit shell is a discarded part. Its biological activity remains to be elucidated. In this study, we investigated the capacity of C. japonica fruit shell extract (CJFSE) for hair loss mitigation. Methods: MTT assay, spheroid culture and quantitative RT‐PCR were performed to observe the proliferative effect of CJFSE on hair follicle dermal papilla cells (HFDPCs). Effects of CJFSE on DHT‐induced hair loss were confirmed by Dkk‐1 ELISA, β‐galactosidase (β‐gal) and 5α‐reductase activity assay. In addition, effects of CJFSE on oxidative stress were confirmed through DPPH and ROS production assays. Results: CJFSE increased the proliferation and spheroid size of HFDPCs. Expression levels of VEGF‐A, Wnt‐1, c‐Myc and Cyclin D1 were upregulated by CJFSE. CJFSE also suppressed 5α‐reductase activity and DHT‐induced decrease in cell proliferation, Dkk‐1 secretion and β‐gal activity. Moreover, CJFSE showed DPPH scavenging activity and ameliorated hydrogen peroxide‐induced ROS production and β‐gal activity. Finally, gallic acid and protocatechuic acid were observed in CJFSE through HPLC analysis. Conclusion: CJFSE has the potential to alleviate hair loss by promoting hair cell growth and suppressing effects of DHT and oxidative stress on hair. [ABSTRACT FROM AUTHOR]

Androgenic alopecia (AGA) is the most common type of hair loss, where local high concentrations of dihydrotestosterone (DHT) in the scalp cause progressive shrinkage of the hair follicles, eventually contributing to hair loss. Due to the limitations of existing methods to treat AGA, the use of multi-origin mesenchymal stromal cell-derived exosomes has been proposed. However, the functions and mechanisms of action of exosomes secreted by adipose mesenchymal stromal cells (ADSCs-Exos) in AGA are still unclear. Using Cell Counting Kit-8 (CCK8) analysis, immunofluorescence staining, scratch assays, and Western blotting, it was found that ADSC-Exos contributed to the proliferation, migration, and differentiation of dermal papilla cells (DPCs) and up-regulated the expression of cyclin, β-catenin, versican, and BMP2. ADSC-Exos also mitigated the inhibitory effects of DHT on DPCs and down-regulated transforming growth factor-beta1 (TGF-β1) and its downstream genes. Moreover, high-throughput miRNA sequencing and bioinformatics analysis identified 225 genes that were co-expressed in ADSC-Exos; of these, miR-122-5p was highly enriched and was found by luciferase assays to target SMAD3. ADSC-Exos carrying miR-122-5p antagonized DHT inhibition of hair follicles, up-regulated the expression of β-catenin and versican in vivo and in vitro, restored hair bulb size and dermal thickness, and promoted the normal growth of hair follicles. So, ADSC-Exos enhanced the regeneration of hair follicles in AGA through the action of miR-122-5p and the inhibition of the TGF-β/SMAD3 axis. These results suggest a novel treatment option for the treatment of AGA. [ABSTRACT FROM AUTHOR]

Dermal papilla cells (DPCs) are a rich source of nutrients and secrete multiple growth factors that can affect hair growth. As oxidative stress leads to hair loss in humans, it is considered to be one of the factors that can impair the function of DPCs. Herb-derived phytochemicals exhibit potent antioxidant activities; therefore, this study investigated whether a set of essential oils (lavender, lemongrass, rosemary, and chamomile oils) promote the hair-growth activity of DPCs. Intracellular reactive oxygen species (ROS) increased markedly in ultraviolet B-irradiated DPCs (50 mJ/cm2) and were efficiently blocked by essential oils. Essential oils upregulated the mRNA and protein levels of phase II enzymes (detoxifying and antioxidant), including heme oxygenase-1, NAD(P)H quinone oxidoreductase-1, and glutathione S-transferase pi. They also upregulated and activated nuclear factor E2-related factor 2, an essential transcription factor for phase II enzymes. Regarding biomarkers for hair growth, essential oils significantly increased vascular endothelial cell growth factor and insulin-like growth factor-1 mRNA levels. In conclusion, phytochemicals in essential oils enhance hair growth through ROS-scavenging activity in DPCs. [ABSTRACT FROM AUTHOR]

Abstract Background Cashmere goats are a heterogeneous hairy mammal. The fineness of cashmere can affect its economic value. Therefore, in this study, we used transcriptome sequencing techniques to analyze the gene expression profiles of the skin tissues of cashmere goats with different cashmere fineness. The selected candidate genes were functionally verified with the secondary hair follicle hair papillary cells of cashmere goats. Results We identified 479 DEGs, of which 238 mRNAs were up-regulated in the fine velvet group and 241 mRNA were down-regulated. Based on functional annotation and protein interaction network analysis, we found some genes that may affect the fineness of cashmere, including SOX18, SOX4, WNT5A, IGFBP4, KAP8, KRT36, and FA2H. Using qRT-PCR, Western blot, CCK-8 cell viability detection, EDU cell proliferation detection, and flow cytometry, we found that overexpression of the FA2H gene could promote the proliferation of secondary hair follicle DPCs in cashmere goats. At the same time, we proved that FA2H could regulate the expression levels of the FGF5 and BMP2 genes in DPCs. Conclusion The results of this study provide a useful reference for the genetics and breeding of Jiangnan cashmere goats and goat genome annotation, and provide an experimental basis for improving cashmere quality of the cashmere goat.

Introduction: Regenerative medicine is a promising approach for hair loss; however, its primary challenge is the inductivity of human dermal papilla cells (DPCs), which rapidly lose hair growth-inducing properties in 2D culture. Despite extensive research efforts to construct DPCs, current 3D microenvironments fabricated to restore hair inductivity remain insufficient. Objectives: Here, we aimed to fabricate ECM-enriched controllable vascularized dermal papilla (DP) spheroids that highly mimic in vivo DPCs microenvironments to restore their hair inductivity. Methods: We employed layer-by-layer (LbL) self-assembly using gelatin and alginate to construct nanoscale biomimetic ECM for DPCs, with Ca2+ as a cross-linking agent to create controllable DP spheroids. DPCs were also co-cultured with human umbilical vein endothelial cells to construct vascularized DP spheroids. Immunofluorescence staining and angiography was used to detect angiogenesis in vitro and in vivo. RNA sequencing and in vivo implantation were employed to investigate DPCs signature. Results: LbL technology enabled DPCs to aggregate into controllable DP spheroids of size and cell numbers similar to those of primary DP. Vascularization prevented hypoxia-induced necrosis and functioned in association with host vessels post-transplantation. Compared with traditional 3D culture, nanoscale ECM and vascularization were found to restore the transcriptional signature of DPCs and triple hair induction efficiency following engraftment. Conclusion: Our novel biomimetic developmental tissue engineering strategy is a crucial step toward the recovery of human DPC hair inductivity, which would enable the rapid clinical application of large-scale hair regeneration platforms.