Search Results (148)

Hair follicle stem cells (HFSCs) are critical for hair follicle (HF) morphogenesis and cyclic hair regeneration. Periostin (POSTN), an extracellular matrix protein involved in tissue development and skin cell regulation, remains poorly characterized in HFSCs. In this study, we constructed CRISPR/Cas9 vectors targeting POSTN and validated their editing efficiency in primary HFSCs. POSTN editing significantly suppressed cell proliferation and promoted apoptosis. Transcriptomic analysis identified 988 differentially expressed genes (DEGs) enriched in immune responses and MAPK, PI3K–Akt, and cAMP pathways. Metabolomic analysis revealed 98 differential metabolites (DMs) associated with nucleotide metabolism and FoxO, AMPK, and cAMP pathways. Integrated multi-omics analysis showed extensive correlations between DEGs and DMs, and highlighted the cAMP pathway as the core regulatory axis. Western blot (WB) validation confirmed that POSTN editing reduced PKA and CREB phosphorylation, indicating inhibition of the cAMP/PKA/CREB signaling. These findings demonstrate that POSTN regulates HFSCs’ proliferation and apoptosis partially via the cAMP/PKA/CREB pathway, providing novel insights into the functional regulation of HFSCs. Full article

Cashmere goats are widely distributed in the cold, arid and semi-arid remote regions of northern China. Their main economic value is the production of precious cashmere fibers. The differentiation of second hair follicle (SHF) stem cells into hair follicle lineages plays a crucial role in SHF regeneration as well as in the morphogenesis and growth of cashmere fibers; however, its precise molecular mechanism is still unclear. In this study, we found that N⁶-methyladenosine (m⁶A)-circHECA recruiting FUS promoted the differentiation of SHF stem cells into hair follicle lineages through stabilizing FOXM1 mRNA in SHF stem cells, thereby activating the NOTCH pathway in cashmere goats. Furthermore, we confirmed that the m⁶A modification of circHECA is required for the FUS/FOXM1-mediated NOTCH signaling pathway to facilitate the differentiation of SHF stem cells into hair follicle lineages via transfecting circHECA m⁶A-deficient mutants. Our results contribute to elucidating the functional mechanism of m⁶A-circHECA in the differentiation of SHF stem cells into hair follicle lineages in cashmere goats. Full article

Plerixafor is a clinically approved CXCR4 antagonist that mobilizes hematopoietic stem cells by disrupting CXCL12/CXCR4 retention signaling. However, its biochemical effects on melanocytes and pigmentation remain unexplored. We investigated how Plerixafor modulates CXCR4 signaling in melanocytes and evaluated its potential as a pro-melanogenic agent using in vitro and in vivo approaches. Human PIG1 melanocytes were treated with 10 nM Plerixafor with or without hydroquinone (HQ), followed by qPCR for MITF and tyrosinase expression, flow cytometry for CXCR4/CXCR7 and integrin profiling, transwell migration assays, β-arrestin siRNA knockdown, Western blotting, subcellular fractionation, and ChIP-qPCR for β-catenin binding to MITF regulatory regions. A murine HQ-induced depigmentation model was used to test topical Plerixafor on pigmentation, hair follicles, melanogenic gene expression, and systemic safety markers. Plerixafor significantly increased MITF and tyrosinase mRNA and enhanced melanocyte migration while counteracting HQ-induced suppression of melanogenic genes. In addition, it reduced cell-surface CXCR4 (consistent with β-arrestin-mediated receptor internalization) without altering CXCR7, c-KIT, or N-cadherin. β-Arrestin knockdown abolished Plerixafor-induced ERK phosphorylation and melanogenic responses, confirming β-arrestin dependence. Plerixafor promoted β-catenin nuclear translocation and direct β-catenin occupancy at MITF promoter/enhancer TCF/LEF motifs. In vivo, topical Plerixafor restored HQ-induced depigmentation, increased hair follicle number and melanin content, and upregulated cutaneous MITF and tyrosinase without hepatic, renal, or inflammatory toxicity. Plerixafor functions as a biased CXCR4 ligand in melanocytes, influencing the β-arrestin–β-catenin–MITF signaling axis to drive melanogenesis and re-pigmentation. These findings identify β-arrestin-dependent CXCR4 signaling as a tractable pharmacologic mechanism for therapeutic re-pigmentation in pigmentary disorders. Full article

Hair follicle (HF) stem cells are multipotent adult stem cells that play a key role in the hair follicle cycle. However, it remains poorly understood how the outer root sheath (ORS)—specifically, the stem cells in the bulge region of the hair follicle—promotes skin repair. This study aims to investigate the role of bulge stem cells in tissue growth and repair and to determine whether the ORS of transplanted hair follicles can facilitate skin repair. We further seek to elucidate the mechanisms by which bulge stem cells contribute to hair follicle development, regeneration, and skin wound healing. In this study, hair follicle samples were obtained from neonatal mice using microdissection. Hair follicle morphology was assessed by Sirius red staining, H&E staining, and transmission electron microscopy. Immunofluorescence staining was used to detect changes in CD34 and SOX9 protein expression. Additionally, microdissection-based hair follicle transplantation and Western blotting were employed to investigate protein activation and inhibition in the Wnt/β-catenin signaling pathway. The results show that the hair follicle bulge, inner root sheath, and dermal papilla all increase in size as hair follicles grow, with each structure growing relatively rapidly on day 7. Treatment with Teplinovivint effectively inhibits the expression of Wnt/β-catenin signaling pathway-related proteins and hair follicle stem cell markers. Damaged hair follicle tissues cultured in vitro are capable of self-repair. At the transplantation site, the skin gradually closes as the outer root sheath wound heals. In contrast, the central region of the outer root sheath becomes progressively filled with numerous dividing cells and extracellular matrix. The inner portion of the outer root sheath is densely populated with cells, and the markers CD34 and SOX9 are also widely distributed. This indicates that activation of the Wnt/β-catenin signaling pathway enhances the proliferation and differentiation of hair follicle stem cells, thereby promoting hair follicle growth, repair of damaged follicles, and healing of skin wounds. Furthermore, this study demonstrates the feasibility of using transplanted outer root sheath (ORS) to repair skin wounds—specifically, the potential to achieve large-scale hair regeneration from a limited number of hair follicle stem cells—providing a new approach for the clinical treatment of skin injury disorders. Nevertheless, achieving long-term, stable, and scalable clinical translation of ORS stem cells for hair follicle regeneration remains a major challenge. Full article

Cutaneous Radiation Injuries (CRIs) and wounds within an area of radiation exposure (combined injury, CI) are a significant concern for nuclear accidents and radiation combat/terrorist events. CRIs and CI present unique clinical challenges, and effective countermeasures are urgently needed. Here we describe a murine model of CRI and CI in C57BL/6 mice using 16.9 Gy thoracic X-ray irradiation (5.3 Gy/min, 160 kV) ± experimental wound administered immediately. Wound repair and radiation-induced dermatitis were assessed after irradiation. Our previous studies showed that genistein (200 mg/kg, s.c.), administered 24 h prior to irradiation prevented radiation injuries in two murine models. We investigated the effects of genistein in the CI model. Macroscopic and histological analyses showed that radiation significantly delayed wound closure, although wounds did not significantly alter the progression of radiation dermatitis. Genistein improved the early rate of wound closure and significantly reduced dermatitis in mice. Histological analysis showed that genistein improved skin structure and reduced inflammation and fibrosis. Immunohistochemistry showed that genistein attenuated radiation-induced cyclin-dependent kinase inhibitor 1 (p21/waf1) and α-smooth muscle actin and preserved K15 positive skin adult stem cells. These findings suggest that genistein may be an effective prophylactic against CRIs and CI. Full article

Hypertrophic scars are characterized by excessive collagen deposition, fibrotic remodeling, and functional impairment. However, the ability of current models is limited in recapitulating human pathology. This study presents a novel approach using induced pluripotent stem cell-derived scar organoids to model hypertrophic scar characteristics in vitro. Following established protocols, human pluripotent stem cells were differentiated into skin organoids and induced fibrotic transformation by treatment with TGF-β1 (10 ng/mL) and hypoxia (5% O₂) from day 45 onward. Scar organoids exhibited significant contraction and increased collagen I deposition compared with skin organoids. Immunofluorescence analysis showed reduced LHX2 expression, indicating loss of hair follicle development, while collagen I expression was significantly elevated. Dark-field imaging revealed marked morphological divergence between skin and scar organoids. RNA sequencing revealed distinct transcriptomic profiles. Expression of hair follicle-associated gene families (KRT and KRTAP) was upregulated in scar organoids, whereas epidermal structure-related genes (KRT4, KRT7, CLDN7, and WNT7) were downregulated. These findings demonstrate that iPSC-derived scar organoids successfully recapitulate key features of human hypertrophic scars, including excessive collagen production, loss of skin appendage development, and contractile behavior. This platform offers potential for future applications in drug screening, precision medicine, and understanding the molecular mechanisms underlying scar formation. Full article

Exosomes are revolutionizing skincare as natural messengers for cell communication, yet their transition into cosmetics is often limited by the ethical and regulatory hurdles of their animal or human sourcing. This study describes the development and validation of vegan exosome-like biomimetic vesicles (EBVs) generated from the microalgae Chlamydomonas reinhardtii that reproduce the structural and functional logic of mammalian exosomes. Their structural biomimetism was confirmed through physical, lipidomic, and proteomic characterizations, revealing bilamellar vesicles (average diameter ~160 nm) containing 109 membrane lipids and 1369 proteins. Their functional biomimetism was assessed via 3′ mRNA sequencing, which showed that the EBVs induced transcriptional responses in human fibroblasts functionally analogous to human-derived exosomes in matrix-remodeling and anti-aging pathways. In vitro, the EBVs showed a 166.7% higher dermal delivery bias than standard liposomes and accelerated wound healing. Ex vivo, 2% EBVs protected skin explants against UV-A stress, showing 92% protective efficacy for excessive melanin production upon oxidative stress. Furthermore, the EBVs supported hair follicle anagen markers and follicle stem cell metabolism, significantly upregulating SOX9 (p = 0.0022). A 56-day placebo-controlled clinical study confirmed significant improvements in wrinkle depth (−12.2%), elasticity (+4.9%), and radiance (+20.0%). These results position EBVs as a scalable, high-performance alternative for next-generation anti-aging cosmetic applications. Full article

Hair follicles (HFs) are highly accessible mini-organs that house diverse somatic and stem cell populations with broad therapeutic potential. In this study, we investigate the untapped utility of plucked HFs as a non-invasive tissue source for regenerative medicine. We demonstrate the successful isolation and expansion of keratinocytes and mesenchymal stem cells (MSCs) from plucked follicles using an enzyme-free explant culture method. HF-derived keratinocytes retained their epithelial identity and were efficiently reprogrammed into induced pluripotent stem cells (iPSCs). These iPSCs were further directed toward definitive endoderm and pancreatic progenitor fates, confirming their robust autologous regenerative capacity. Flow cytometric analysis of HF-MSCs validated a characteristic mesenchymal profile, and these cells exhibited classical trilineage plasticity alongside the ability to differentiate into dopaminergic neural progenitors. Furthermore, proteomic and vesicular characterization of the autologous HF secretome (aHFS) revealed a rich enrichment of regenerative cytokines and exosomes. The aHFS demonstrated potent wound-healing bioactivity in vitro. Collectively, these findings establish the plucked hair follicle as a highly practical, scalable source for both cell-based and cell-free therapies, highlighting the clinical value of early-stage follicular biobanking for personalized medicine. Full article

Dermal papilla (DP) cells orchestrate hair follicle growth and cycling by secreting signaling molecules that stimulate follicular epithelial stem cells. The signal peptide CUB-EGF-like domain-containing protein 3 (SCUBE3) was recently identified as a potent anagen stimulator secreted by DP cells. Ageratum houstonianum ethanolic extract (AHE) and its active constituent agerarin exhibit anti-inflammatory properties; however, their effects on hair follicle growth remain unclear. This study aimed to investigate the effects of AHE and agerarin on SCUBE3 expression in primary human DP cells and to elucidate the underlying molecular signaling pathway. Cell viability was assessed by measuring cell confluency. Ex vivo hair growth was analyzed using organ cultures of human hair follicles. Gene and protein expression were determined using reverse transcription-PCR, immunoblot analysis, immunofluorescent staining, tyramide signal amplification-based multiplex immunohistochemistry, and gene promoter-reporter assay in primary human follicle DP cells. In a hair follicle organ culture model, both AHE and agerarin increased the population of the anagen phase and promoted hair shaft elongation. AHE and agerarin significantly upregulated SCUBE3 expression at both the mRNA and protein levels. Mechanistically, AHE and agerarin induced activator protein-1 (AP-1) expression by activating mitogen-activated protein kinase signaling pathways, thereby increasing SCUBE3 gene promoter activity. AHE and agerarin promoted hair follicle growth by upregulating SCUBE3 expression via activation of the MAPK–AP-1 signaling axis. In conclusion, AHE and agerarin may serve as potential therapeutic agents for the prevention and treatment of alopecia (hair loss). Full article

Skin and hair follicles regenerate through coordinated stem cell niches and cyclic signaling associated with transitions among anagen, catagen, and telogen phases. In alopecia and chronic skin diseases, follicular miniaturization, immune dysregulation, persistent inflammation, impaired vascularization, and a compromised stratum corneum barrier limit the effectiveness of conventional topical and systemic therapies. Bio-nanovesicles (BNVs), including natural extracellular vesicles such as exosomes and microvesicles, as well as engineered artificial or hybrid nanovesicles, offer a targeted, cell-free delivery platform for miRNAs, proteins, and growth factors. By modulating key pathways—Wnt/β-catenin, PI3K/AKT, MAPK/ERK, and TGF-β/BMP—BNVs have the potential to restore regenerative crosstalk, enhance angiogenesis, and help initiate hair and skin repair. Full article

Hair follicles are highly specialized mini-organs within the skin that drive the production of wool and cashmere, traits of major biological and economic importance in sheep and goats. Despite their microscopic size, hair follicles exhibit extraordinary regulatory complexity, integrating genetic programs with seasonal, endocrine, environmental, and epigenetic cues. Although transcriptional networks and signaling pathways underlying follicle morphogenesis and cycling have been extensively investigated, the post-transcriptional mechanisms that fine-tune these processes remain insufficiently understood. MicroRNAs (miRNAs) have emerged as pivotal post-transcriptional regulators that coordinate cell fate determination, lineage commitment, and tissue homeostasis. Growing evidence indicates that miRNAs play essential roles in hair follicle stem cell maintenance, proliferation, differentiation, apoptosis, and organ-level development, functioning through interconnected regulatory networks rather than isolated linear pathways. By modulating the expression of key follicle-determining genes and signaling components, miRNA-mediated regulation shapes follicle formation, cyclic regeneration, and fiber traits. In this review, we synthesize recent advances in miRNA research related to hair follicle biology, with a particular focus on wool- and cashmere-bearing mammals. We integrate findings across species to propose a systems-level framework in which miRNA networks interface with canonical signaling pathways and epigenetic mechanisms to orchestrate follicle development and regeneration. Conserved and species-specific regulatory principles are discussed to bridge fundamental follicle biology with practical applications in fiber production. Overall, this review highlights miRNAs as a critical yet previously underappreciated regulatory layer in hair follicle biology. A deeper understanding of miRNA-mediated control provides new conceptual insights into wool and cashmere development and offers a foundation for future molecular breeding and precision regulation strategies in livestock. Full article

The regeneration and repair of scarless skin tissue remain a significant challenge for full-thickness wounds. Traditional wound management approaches, particularly passive healing through scabbing and conventional mechanical debridement, are frequently associated with significant pain, high infection risks, and abnormal scar formation, often failing to support the regeneration of skin appendages like hair follicles. In recent years, collagen-based scaffolds have been widely adopted in tissue-engineered skin substitutes owing to their favorable biocompatibility. However, their simplistic, single-component architecture inherently lacks the dynamic, cell-instructive microenvironment found in native skin, which not only compromises the long-term survival and functional integration of seeded cells but also directly leads to insufficient reconstruction of the dermo-epidermal junction, thereby impairing skin barrier function and ultimately limiting overall regenerative efficacy. In this study, we propose a biomimetic multilayer composite scaffold system in which decellularized amniotic membrane matrix (AM) is combined with fibroblast-laden collagen gel (FCG) and seeded with epidermal stem cells (EpiSCs). This bionic skin (denoted as AM-FCG-EpiSCs) is designed to achieve hierarchical regeneration of full-thickness skin defects. Compared with injured skin treated with Moropicin ointment, the injured skin treated with AM-FCG-EpiSCs healed more quickly and regenerated appendages like hair follicles without scarring. The results show that the biomimetic structure of AM-FCG-EpiSCs can mediate dynamic cell–cell interactions and regulate the microenvironment. This breakthrough overcomes the dual challenges of scar suppression and functional restoration in full-thickness skin regeneration, offering an innovative solution for translational medicine. Full article

Hair loss, or alopecia, constitutes a significant and prevalent concern affecting individuals worldwide. Despite the availability of numerous commercial solutions, many individuals continue to experience substantial psychological distress, leading to adverse impact on personal relationships, social interactions, and occupational performance. The limitations of conventional treatments, such as oral medication with potential systemic side effects and topical applications with localized adverse events, have driven the exploration of alternative therapies. Emerging localized injectable treatments for hair regrowth (PRP, stem cells, exosomes) offer a promising avenue for addressing this persistent issue. These injectable therapies hold the potential to minimize the systemic side effects often associated with oral medications, while also mitigating the localized adverse events that can arise from topical applications. This narrative review provides a comprehensive overview of the medical state-of-the-art in off-label injectable hair regrowth treatments, delving into the diverse range of available options. A critical component of this narrative review involves a thorough evaluation of relevant clinical studies, assessing the efficacy and safety profiles of these emerging therapies. Furthermore, detailed attention is given to injection techniques and administration protocols, crucial factors in optimizing treatment outcomes. These evolving therapies represent a significant advancement in the field of scalp regenerative medicine. By stimulating hair follicle reactivation, these treatments aim to promote sustained and natural hair growth, providing individuals with more effective and durable solutions. The enhanced safety profiles of these injectable therapies, compared to conventional systemic pharmacological treatments (minoxidil, finasteride), offer a substantial improvement in patient care, addressing a widespread clinical need. Full article

Androgenetic alopecia (AGA) is a highly prevalent and progressive disorder characterized by follicular miniaturization and dysregulation of the hair follicle microenvironment. Although minoxidil (MXD) and finasteride remain first-line therapies, their long-term efficacy is limited by poor follicular bioavailability, systemic side effects, and suboptimal patient compliance. In recent years, nanotechnology-based strategies have emerged as promising alternatives by enabling efficient follicular targeting and controlled therapeutic delivery. This review critically summarizes recent advances in nanotechnology-enabled approaches for AGA management, including nanocarrier-based formulations and nanotechnology-based microneedle systems. Beyond functioning as passive drug carriers, emerging nanoplatforms increasingly act as active modulators of the follicular niche by attenuating oxidative stress, inflammation, impaired angiogenesis, and stem cell dysfunction—key pathological drivers of AGA progression—thereby representing a conceptual shift from delivery-centered to microenvironment-remodeling strategies. To enhance translational relevance, we compare nanotechnology-based therapies with conventional treatments in terms of efficacy, safety, and clinical feasibility, and summarize representative preclinical studies, patent landscapes, and ongoing or completed clinical trials. Finally, key challenges related to safety evaluation, manufacturing reproducibility, and regulatory classification are discussed, highlighting nanotechnology as a promising framework for next-generation, mechanism-oriented AGA therapy and precision trichology. Full article

The number of pet dogs is increasing, and the number of working dogs (e.g., guide dogs, police dogs) is also gradually increasing. Skin wounds are a common clinical problem in dogs and tend to be more common in the clinic as mechanical wounds. The healing process of skin wounds is often influenced by a variety of factors, including infection, nutritional status, and immune response, while wound healing is more difficult in dogs with diabetes or aging dogs. Mesenchymal stem cells (MSCs) play an important role in skin healing and regeneration with their multidirectional differentiation potential and immunomodulatory function. However, the application of MSCs alone for the treatment of skin wounds may have certain limitations, such as low cell survival and a lack of localization. Therefore, it is important to find methods that can enhance the therapeutic effect of MSCs. Secreted protein acidic and rich in cysteine (SPARC), an extracellular matrix protein widely involved in regulating biological processes such as cell proliferation, migration, and matrix production, may enhance the efficacy of MSCs in skin wound healing. This study aims to systematically evaluate the therapeutic efficacy of SPARC-overexpressing adipose-derived mesenchymal stem cells (ADSCs) in promoting skin wound healing by establishing wound models in normal, diabetic, and aged mice and dogs, thereby validating their potential under diverse physiological and pathological conditions. For in vitro validation, we used hydrogen peroxide (H₂O₂) to induce Human Umbilical Vein Endothelial Cell (HUVEC) and Human Keratinocyte Cell (HaCaT) injury. All animals were randomly assigned to six experimental groups as follows: (1) Model group: Untreated wound (negative control); (2) HY group: Hydrogel alone (vehicle control); (3) Con group: Control-ADSCs (cell control); (4) Con-Exo&HY group: Control-ADSC exosomes in hydrogel; (5) SPARC group: oe-SPARC-ADSCs (treatment); (6) SPARC-Exo&HY group: oe-SPARC-ADSC exosomes in hydrogel (treatment). Separately, HUVEC and HaCaT cells were assigned to four experimental conditions: a blank control group, a model group, a control-ADSC-treated group, and an oe-SPARC-ADSC-treated group. ADSCs modified by SPARC significantly promoted re-epithelialization integrity, collagen deposition, inflammation reduction, angiogenesis, and hair follicle regeneration during wound healing in dog skin. HUVEC and HaCaT cells proliferated after adding oe-SPARC-ADSCs cell supernatant. Meanwhile, quantitative proteomic sequencing data analysis showed that SPARC could promote skin wound healing by enhancing cell adhesion, hyaluronic acid binding, and vascular smooth muscle contraction of ADSCs. Both in vitro cellular assays and in vivo wound-healing models suggest that the combination of SPARC and ADSCs for the treatment of skin wounds has broad application prospects. Full article