Search Results (30)

Androgenetic alopecia (AGA) is a common progressive hair loss disorder driven by elevated dihydrotestosterone (DHT) levels, leading to follicular miniaturization. This study investigated sulforaphane-rich broccoli sprout extract (BSE) as a potential oral therapy for AGA. BSE exhibited dose-dependent proliferative and migratory effects on keratinocytes, dermal fibroblasts, and dermal papilla cells, showing greater in vitro activity than sulforaphane (SFN) and minoxidil under the tested conditions, while maintaining low cytotoxicity. In a testosterone-induced AGA mouse model, oral BSE significantly accelerated hair regrowth, with 20 mg/kg achieving 99% recovery by day 15, alongside increased follicle length, density, and hair weight. Mechanistically, BSE upregulated hepatic and dermal DHT-metabolizing enzymes (Akr1c21, Dhrs9) and activated Wnt/β-catenin signaling in the skin, suggesting dual actions via androgen metabolism modulation and follicular regeneration. Pharmacokinetic analysis revealed prolonged SFN plasma exposure following BSE administration, and in silico docking showed strong binding affinities of key BSE constituents to Akr1c2 and β-catenin. No systemic toxicity was observed in liver histology. These findings indicate that BSE may serve as a safe, effective, and multitargeted natural therapy for AGA. Further clinical studies are needed to validate its efficacy in human populations. Full article

Small extracellular vesicles (sEVs) derived from mesenchymal stem cells have emerged as promising therapeutic agents in regenerative dermatology. This study evaluated the safety and efficacy of Bio-Pulsed avian mesenchymal stem cell-derived sEVs (AMSC-sEVs), topically applied for hair follicle stimulation and skin rejuvenation. Two prospective, single-arm clinical trials were conducted: one involving 30 participants using a hair ampoule over 60 days, and the other involving 30 participants applying a facial essence for 28 days. Objective measurements demonstrated significant improvements in the anagen/telogen hair ratio, reduced shedding, increased collagen density, and reduced wrinkle depth and pigmentation. Small RNA sequencing and qPCR profiling confirmed that Bio-Pulsed AMSC-sEVs were enriched with regenerative microRNAs, such as miR-21-5p and miR-199a-5p, associated with anti-inflammatory and anti-aging effects. No adverse events were reported. These findings suggest that Bio-Pulsed AMSC-sEVs may offer a safe, non-invasive, and cell-free approach to enhance skin and hair regeneration in human subjects. Full article

Hair loss is often associated with oxidative stress and mitochondrial dysfunction in human follicle dermal papilla cells (HFDPCs), resulting in impaired cellular function and follicle degeneration. Thus, many studies have been conducted on natural plants aimed at inhibiting hair loss. This study investigated the therapeutic potential of exosomes derived from the rhizomes of Iris germanica L. (Iris-exosomes) in HFDPCs damaged by dihydrotestosterone (DHT). Iris-exosomes significantly reduced reactive oxygen species (ROS) levels, restoring mitochondrial membrane potential and ATP production, thereby mitigating oxidative stress and improving mitochondrial function. These effects occurred alongside enhanced cellular processes critical for hair follicle regeneration, including increased cell migration, alkaline phosphatase (ALP) activity, and three-dimensional (3D) spheroid formation, which replicates the follicle-like microenvironment and promotes inductive potential. Furthermore, Iris-exosomes stimulated the Wnt/β-catenin signaling pathway by enhancing glycogen synthase kinase-3β (GSK-3β), AKT, and extracellular signal-regulated kinase (ERK), leading to β-catenin stabilization and nuclear translocation, thereby supporting the expression of genes essential for hair growth. Taken together, these findings suggest that Iris-exosomes can be promising ingredients for alleviating hair loss. Full article

Abnormalities in epidermal keratinocyte proliferation are a characteristic feature of a range of dermatological conditions. These include hyperproliferative states in psoriasis and dermatitis as well as hypoproliferative states in chronic wounds. This emphasises the importance of investigating the proliferation kinetics under conditions of healthy skin and identifying the key regulators of epidermal homeostasis, maintenance, and recovery following wound healing. Animal models contribute to our understanding of human epidermal self-renewal. Human skin xenografting overcomes the ethical limitations of studying human skin during regeneration. The application of this approach has allowed for the identification of a single population of stem cells and both slowly and rapidly cycling progenitors within the epidermal basal layer and the mapping of their location in relation to rete ridges and hair follicles. Furthermore, we have traced the dynamics of the proliferation pattern reorganization that occurs during epidermal regeneration, underlining the role of YAP activity in epidermal relief formation. Full article

Wound-induced hair-follicle neogenesis (WIHN) is the phenomenon of regenerating new hair follicles from wounds in mammals. The WIHN involves both developmental and adult wound-healing processes. Moreover, the WIHN is regulated by a variety of factors, particularly multiple molecular signaling pathways produced in several types of cells. Here, the role of multiple signaling in different types of cells in WIHN is comprehensively described. Furthermore, the lack of dermal γδ T cells in the human scalp has hindered the clinical application of WIHN, but the development of drugs such as Wnt signaling activators is increasing the effectiveness of WIHN in humans. Overall, understanding the underlying mechanisms that regulate WIHN may help treat skin diseases, including alopecia. Full article

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. Full article

Introduction: Mesenchymal stem cells (MSCs) have been introduced as a promising treatment for diabetic wounds. The effects of stem cell therapy are thought to be caused by bioactive molecules secreted by stem cells. Stem cell-based gene therapies can target bioactive molecules. Therefore, treatment using conditioned medium (CM) derived from genetically engineered stem cells has been proposed as an alternative option for diabetic ulcer care. Methods: MSCs derived from human umbilical cords were obtained and engineered to overexpress the angiogenin-1 gene (MSCs^Ang1) through plasmid transfection. This study extracted conditioned medium from MSCs (MSC-CM) or MSCs^Ang1(MSC^Ang1-CM) for wound treatment applications. Via in vitro experiments, the proangiogenic effects of MSC^Ang1-CM were assessed via the migration and tube formation of human umbilical vein endothelial cells (HUVECs). Furthermore, the efficacy of MSC^Ang1-CM in promoting wound healing, re-epithelialization, hair follicle, and angiogenesis was evaluated via a diabetic mouse skin defect model. Results: In vitro assays demonstrated that MSC^Ang1-CM significantly enhanced HUVECs’ functions, including migration and tube formation. In vivo assays revealed that MSC^Ang1-CM exhibited notable advancements in healing speed, re-epithelialization, hair follicle, and angiogenesis. Conclusion: These results indicate that MSC^Ang1-CM can promote wound healing in diabetic mice and make the vascular structure in regenerated tissues more stable without inducing tissue fibrosis, providing a new therapeutic strategy for treating diabetic skin wounds. This provides a valuable theoretical basis for further research on regenerative medicine and cell therapy. Full article

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. Full article

Prostaglandin E₂ (PGE₂) is known to be effective in regenerating tissues, and bimatoprost, an analog of PGF_2α, has been approved by the FDA as an eyelash growth promoter and has been proven effective in human hair follicles. Thus, to enhance PGE₂ levels while improving hair loss, we found dihydroisoquinolinone piperidinylcarboxy pyrazolopyridine (DPP), an inhibitor of 15-hydroxyprostaglandin dehydrogenase (15-PGDH), using DeepZema^®, an AI-based drug development program. Here, we investigated whether DPP improved hair loss in human follicle dermal papilla cells (HFDPCs) damaged by dihydrotestosterone (DHT), which causes hair loss. We found that DPP enhanced wound healing and the expression level of alkaline phosphatase in DHT-damaged HFDPCs. We observed that DPP significantly down-regulated the generation of reactive oxygen species caused by DHT. DPP recovered the mitochondrial membrane potential in DHT-damaged HFDPCs. We demonstrated that DPP significantly increased the phosphorylation levels of the AKT/ERK and activated Wnt signaling pathways in DHT-damaged HFDPCs. We also revealed that DPP significantly enhanced the size of the three-dimensional spheroid in DHT-damaged HFDPCs and increased hair growth in ex vivo human hair follicle organ culture. These data suggest that DPP exhibits beneficial effects on DHT-damaged HFDPCs and can be utilized as a promising agent for improving hair loss. Full article

Fibroblast growth factor 5 (FGF5) plays key roles in promoting the transition from the anagen to catagen during the hair follicle cycle. The sheep serves as an excellent model for studying hair growth and is frequently utilized in various research processes related to human skin diseases. We used the CRISPR/Cas9 system to generate four FGF5-edited Dorper sheep and only low levels of FGF5 were detected in the edited sheep. The density of fine wool in GE sheep was markedly increased, and the proportion of fine wool with a diameter of 14.4–20.0 μm was significantly higher. The proliferation signal in the skin of gene-edited (GE) sheep was stronger than in wild-type (WT) sheep. FGF5 editing decreased cortisol concentration in the skin, further activated the activity of antioxidant enzymes such as Glutathione peroxidase (GSH-Px), and regulated the expression of Wnt signaling pathways containing Wnt agonists (Rspondins, Rspos) and antagonists (Notum) in hair regeneration. We suggest that FGF5 not only mediates the activation of antioxidant pathways by cortisol, which constitutes a highly coordinated microenvironment in hair follicle cells, but also influences key signals of the Wnt pathway to regulate secondary hair follicle (SHF) development. Overall, our findings here demonstrate that FGF5 plays a significant role in regulating SHF growth in sheep and potentially serves as a molecular marker of fine wool growth in sheep breeding. Full article

Treatment of chronic wounds is challenging, and the development of different formulations based on insulin has shown efficacy due to their ability to regulate oxidative stress and inflammatory reactions. The formulation of insulin with polysaccharides in biohybrid hydrogel systems has the advantage of synergistically combining the bioactivity of the protein with the biocompatibility and hydrogel properties of polysaccharides. In this study, a hydrogel formulation containing insulin, chitosan, and hydroxypropyl methyl cellulose (Chi/HPMC/Ins) was prepared and characterized by FTIR, thermogravimetric, and gel point analyses. The in vitro cell viability and cell migration potential of the Chi/HPMC/Ins hydrogel were evaluated in human keratinocyte cells (HaCat) by MTT and wound scratch assay. The hydrogel was applied to excisional full-thickness wounds in diabetic mice for twenty days for in vivo studies. Cell viability studies indicated no cytotoxicity of the Chi/HPMC/Ins hydrogel. Moreover, the Chi/HPMC/Ins hydrogel promoted faster gap closure in the scratch assay. In vivo, the wounds treated with the Chi/HPMC/Ins hydrogel resulted in faster wound closure, formation of a more organized granulation tissue, and hair follicle regeneration. These results suggest that Chi/HPMC/Ins hydrogels might promote wound healing in vitro and in vivo and could be a new potential dressing for wound healing. Full article

Background: People lose between 50 and 100 hairs a day and generate new ones from stem cells in hair follicles, but in those suffering from baldness, the stem cells remain inactive and are unable to regenerate new hair. Although 9% of hair follicles remain in telogen at any time, a variety of factors, including growth factors and cytokines, promote the transition from telogen to anagen and the subsequent stimulation of hair growth. Methods: We compared in vitro, on cultures of human hair follicles, the effect on hair growth and regeneration of the dermal papilla of plant-derived nanovesicles, exosomes from cord blood stem cells and bovine colostrum, a mixture of growth factors and cytokines purified from bovine colostrum, called GF20, and a new compound called HAIR & SCALP COMPLEX obtained by adding exosomes isolated from colostrum to GF20. Results: The analyses demonstrated a significant increase in the growth of the bulb and the regeneration of the dermal papilla in the samples treated with HAIR & SCALP COMPLEX compared to the other elements tested. Conclusions: In this research, we propose a possible new treatment that could help significantly slow down hair loss and encourage new hair growth: HAIR & SCALP COMPLEX. Full article

Apoptosis is a physiological process that occurs in all cell types of the human body, and it profoundly changes the fate of hair by affecting hair follicle cells. This review outlines the cellular changes, intrinsic biochemical characteristics, and mechanisms underlying apoptosis and summarizes the hair follicle life cycle, including development, cycle stages, and corresponding cellular changes. Finally, the relationship between apoptosis and the hair cycle is discussed and the significance of apoptosis in hair loss conditions and drug treatments is highlighted. Apoptosis induces cellular changes and exhibits distinctive properties through intricate signaling pathways. Hair follicles undergo cyclic periods of growth, regression, and dormancy. Apoptosis is closely correlated with the regression phase by triggering hair follicle cell death and shedding. Regulation of apoptosis in hair follicles plays an essential role in hair loss due to maladies and drug treatments. Mitigating apoptosis can enhance hair growth and minimize hair loss. A comprehensive understanding of the correlation between apoptosis and the hair cycle can facilitate the development of novel treatments to prevent hair loss and stimulate hair regeneration. Full article

For decades, tissue regeneration has been a challenging issue in scientific modeling and human practices. Although many conventional therapies are already used to treat burns, muscle injuries, bone defects, and hair follicle injuries, there remains an urgent need for better healing effects in skin, bone, and other unique tissues. Recent advances in three-dimensional (3D) printing and real-time monitoring technologies have enabled the creation of tissue-like membranes and the provision of an appropriate microenvironment. Using tissue engineering methods incorporating 3D printing technologies and biomaterials for the extracellular matrix (ECM) containing scaffolds can be used to construct a precisely distributed artificial membrane. Moreover, advances in smart sensors have facilitated the development of tissue regeneration. Various smart sensors may monitor the recovery of the wound process in different aspects, and some may spontaneously give feedback to the wound sites by releasing biological factors. The combination of the detection of smart sensors and individualized membrane design in the healing process shows enormous potential for wound dressings. Here, we provide an overview of the advantages of 3D printing and conventional therapies in tissue engineering. We also shed light on different types of 3D printing technology, biomaterials, and sensors to describe effective methods for use in skin and other tissue regeneration, highlighting their strengths and limitations. Finally, we highlight the value of 3D bioengineered membranes in various fields, including the modeling of disease, organ-on-a-chip, and drug development. Full article

Alopecia is a common medical condition affecting both sexes. Dermal papilla (DP) cells are the primary source of hair regeneration in alopecia patients. Therapeutic applications of extracellular vesicles (EVs) are restricted by low yields, high costs, and their time-consuming collection process. Thus, engineered nanovesicles (eNVs) have emerged as suitable therapeutic biomaterials in translational medicine. We isolated eNVs by the serial extrusion of fibroblasts (FBs) using polycarbonate membrane filters and serial and ultracentrifugation. We studied the internalization, proliferation, and migration of human DP cells in the presence and absence of FB-eNVs. The therapeutic potential of FB-eNVs was studied on ex vivo organ cultures of human hair follicles (HFs) from three human participants. FB-eNVs (2.5, 5, 7.5, and 10 µg/mL) significantly enhanced DP cell proliferation, with the maximum effect observed at 7.5 µg/mL. FB-eNVs (5 and 10 µg/mL) significantly enhanced the migration of DP cells at 36 h. Western blotting results suggested that FB-eNVs contain vascular endothelial growth factor (VEGF)-a. FB-eNV treatment increased the levels of PCNA, pAKT, pERK, and VEGF-receptor-2 (VEGFR2) in DP cells. Moreover, FB-eNVs increased the human HF shaft size in a short duration ex vivo. Altogether, FB-eNVs are promising therapeutic candidates for alopecia. Full article