Search Results (45)

Androgenetic alopecia (AGA), the most prevalent form of hair loss worldwide, faces significant therapeutic challenges due to high costs and limited efficacy of current interventions, necessitating safer and more effective solutions. Periplaneta americana (L.)-derived PA-011, endowed with anti-inflammatory and antioxidant properties, has demonstrated notable hair growth-promoting effects in AGA mouse models. This study employed LC-MS/MS, peptidomics, and network pharmacology to characterize PA-011’s chemical composition and predict its potential targets in AGA pathogenesis. Using Western blot and RT-qPCR, PA-011 intervention significantly inhibited inflammatory responses and oxidative stress levels in mouse skin tissues. Concurrently, PA-011 activated the proliferative potential of hair follicle stem cells, as demonstrated by upregulated expression of the cell proliferation marker Ki67, and activated the Wnt/β-catenin signaling pathway in DHT-induced AGA mice. Transcriptomic and metabolomic analyses revealed multi-target effects of PA-011, including modulation of PI3K-Akt/MAPK pathways, pentose phosphate metabolism, and amino acid biosynthesis. 16S rRNA sequencing and metagenomic analysis showed that AGA disrupts skin microbial homeostasis, while PA-011 intervention normalized the microbiota composition. Topical application of PA-011 promoted robust hair regrowth without detectable toxicity in safety assessments. This preclinical study establishes PA-011 as a promising candidate for AGA therapy, warranting further translational investigation. Full article

With alopecia affecting millions globally, recent advancements in the understanding of hair follicle biology have driven the development of novel therapies focused on hair regrowth. This review discusses two emerging therapeutic strategies: hair follicle neogenesis and the modulation of the Wnt/B-catenin signaling pathway. Hair follicle neogenesis, a frontier once considered impossible to achieve in adult humans, has recently gained traction due to advancements in stem cell biology and further understanding of the epithelial–mesenchymal interactions that are critical to hair follicle development. Such an approach shows significant potential for addressing conditions leading to hair loss, such as androgenetic and scarring alopecias. The Wnt/B-catenin signaling pathway, a critical intracellular pathway responsible for hair follicle cycles, has gained traction as a target for therapeutic interventions. Studies show that stimulating this pathway leads to hair follicle growth, while its inhibition prompts hair follicle regression. Investigations demonstrate clinical efficacy of small molecule inhibitors and peptides, such as PTD-DBM, which activates the Wnt/β-catenin pathway by interfering with CXXC5, a negative regulator that inhibits pathway activation. Such therapies show potential as more effective treatment options than existing solutions such as finasteride and minoxidil. Adjunctive therapies, such as low-level laser therapy, have also shown clinical efficacy, further highlighting how modulation of this pathway stimulates follicular regrowth. While these novel therapies require further research to validate their efficacy and to gain additional insight into their risk profile, it is clear that alopecia treatment is approaching a new frontier beyond traditional pharmacologic interviews, with regenerative medicine and pathway modulation paving the way forward. Full article

Alopecia areata (AA) is an autoimmune disorder causing non-scarring hair loss, which is often triggered by psychological stress. Conventional treatments, such as corticosteroids and immunotherapy, show variable efficacy and can cause side effects like hair discoloration. Exosome therapy, utilizing extracellular vesicles, presents a promising alternative, though its use in stress-related AA remains underexplored. A 39-year-old male with unifocal AA on the right parietal scalp developed hair loss following emotional distress after his fiancée’s death. Methotrexate and prednisolone were ineffective, prompting a bioregenerative approach using rose stem cell-derived exosomes (RSCEs) combined with thulium laser therapy. Six monthly sessions of RSCEs (20 mg/vial, 10 billion exosomes) were administered, with laser pre-treatment enhancing absorption. Within one month, vellus hair regrowth appeared, progressing to an increased density and pigmentation at three months. By six months, complete regrowth and natural pigmentation were achieved, with reduced inflammation confirmed by trichoscopy. The therapy was well-tolerated, with no adverse effects. This case highlights RSCE therapy as a promising treatment for stress-induced AA, achieving significant regrowth without corticosteroid-related side effects. Further studies are needed to validate its efficacy and refine protocols for broader clinical applications. Full article

Hair loss disorders pose a substantial global health burden, affecting millions of individuals and significantly impacting quality of life. Despite the widespread use of approved therapeutics like minoxidil and finasteride, their clinical efficacy remains limited. These challenges underscore the pressing need for more targeted and effective therapeutic solutions. This review examines the latest innovations in hair loss drug discovery, with a focus on small-molecule inhibitors, biologics, and stem cell-based therapies. By integrating insights from molecular mechanisms and leveraging advancements in research methods, the development of next-generation therapeutics holds the potential to transform the clinical management of hair loss disorders. Future drug development for hair loss disorders should prioritize antibody therapy and cell-based treatments, as these approaches offer unprecedented opportunities to address the limitations of existing options. Antibody therapies enable precise targeting of key molecular pathways involved in hair follicle regulation, providing highly specific and effective interventions. Similarly, cell-based therapies, including stem cell transplantation and dermal papilla cell regeneration, directly address the regenerative capacity of hair follicles, offering transformative potential for hair restoration. 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

As an appendage of the skin, hair protects against ultraviolet radiation and mechanical damage and regulates body temperature. It also reflects an individual’s health status and serves as an important method of expressing personality. Hair loss and graying are significant psychosocial burdens for many people. Hair is produced from hair follicles, which are exclusively controlled by the dermal papilla (DP) at their base. The dermal papilla cells (DPCs) comprise a cluster of specialized mesenchymal cells that induce the formation of hair follicles during early embryonic development through interaction with epithelial precursor cells. They continue to regulate the growth cycle, color, size, and type of hair after the hair follicle matures by secreting various factors. DPCs possess stem cell characteristics and can be cultured and expanded in vitro. DPCs express numerous stemness-related factors, enabling them to be reprogrammed into induced pluripotent stem cells (iPSCs) using only two, or even one, Yamanaka factor. DPCs are an important source of skin-derived precursors (SKPs). When combined with epithelial stem cells, they can reconstitute skin and hair follicles, participating in the regeneration of the dermis, including the DP and dermal sheath. When implanted between the epidermis and dermis, DPCs can induce the formation of new hair follicles on hairless skin. Subcutaneous injection of DPCs and their exosomes can promote hair growth. This review summarizes the in vivo functions of the DP; highlights the potential of DPCs in cell therapy, particularly for the treatment of hair loss; and discusses the challenges and recent advances in the field, from basic research to translational applications. Full article

The degeneration of spiral ganglion neurons (SGNs), which convey auditory signals from hair cells to the brain, can be a primary cause of sensorineural hearing loss (SNHL) or can occur secondary to hair cell loss. Emerging therapies for SNHL include the replacement of damaged SGNs using stem cell-derived otic neuronal progenitors (ONPs). However, the availability of renewable, accessible, and patient-matched sources of human stem cells is a prerequisite for successful replacement of the auditory nerve. In this study, we derived ONP and SGN-like cells by a reliable and reproducible stepwise guidance differentiation procedure of self-renewing human dental pulp stem cells (hDPSCs). This in vitro differentiation protocol relies on the modulation of BMP and TGFβ pathways using a free-floating 3D neurosphere method, followed by differentiation on a Geltrex-coated surface using two culture paradigms to modulate the major factors and pathways involved in early otic neurogenesis. Gene and protein expression analyses revealed efficient induction of a comprehensive panel of known ONP and SGN-like cell markers during the time course of hDPSCs differentiation. Atomic force microscopy revealed that hDPSC-derived SGN-like cells exhibit similar nanomechanical properties as their in vivo SGN counterparts. Furthermore, spiral ganglion neurons from newborn rats come in close contact with hDPSC-derived ONPs 5 days after co-culturing. Our data demonstrate the capability of hDPSCs to generate SGN-like neurons with specific lineage marker expression, bipolar morphology, and the nanomechanical characteristics of SGNs, suggesting that the neurons could be used for next-generation cochlear implants and/or inner ear cell-based strategies for SNHL. Full article

Chronic skin wounds are estimated to affect 6.5 million patients in the US, at a cost of over USD 25 billion. Efforts to prevent and/or treat such wounds will result in reduced morbidity and economic losses. This project is focused on the role of vitamin D signaling in the epidermis in the control of stem cell (SC) activation and function during the initial response to the wounding of the skin, a response that, if defective, contributes to poor wound healing or cancer. In this review, I first describe the anatomy of the skin, focusing first on the epidermis, describing the different cell layers which in a spatial way also represent the differentiation process of the interfollicular epidermis (IFE) as it undergoes continuous regeneration. I then describe the other components of the skin, particularly the hair follicle (HF), which undergoes a cyclic pattern of regeneration. Adult SCs residing in these regenerative tissues play essential roles in the maintenance of these tissues. However, when the skin is wounded, the progeny of SCs from all regions of the HF and IFE contribute to the healing process by changing their initial cell fate to take on an epithelial genotype/phenotype to heal the wound. Although earlier lineage tracing studies helped to define the contributions SCs from the different niches made to wound healing, scRNAseq studies have demonstrated a considerably more nuanced picture. The role of vitamin D signaling will be introduced by reviewing the unique role played by the epidermal keratinocyte first in producing vitamin D and then in metabolizing it into its active form 1,25(OH)2D. 1,25(OH)2D is the principal ligand for the vitamin D receptor (VDR), a transcription factor that helps to mediate the genomic changes in the stem cells in their response to wounding. In these actions, the VDR is regulated by coregulators, of which the steroid receptor coactivator complexes SRC 2 and 3 and the mediator complex (MED) play essential roles. The VDR generally acts in association with other transcription factors such as p63 and β-catenin that can colocalize with the VDR in the genes it regulates. Although much remains to be understood, the role of the VDR in the stem cell response to wounding is clearly essential and quite different from its classic roles in regulating calcium metabolism, although calcium is essential for the actions of vitamin D signaling in the skin. Full article

Androgenetic alopecia is a genetic disorder that commonly causes progressive hair loss in men, leading to diminished self-esteem. Although cannabinoids extracted from Cannabis sativa are used in hair loss treatments, no study has evaluated the effects of germinated hemp seed extract (GHSE) and exosomes derived from the calli of germinated hemp seeds on alopecia. Therefore, this study aimed to demonstrate their preventive effects against alopecia using various methodologies, including quantitative PCR, flow cytometry, ELISA, and immunocytochemistry. Our research highlights the preventive functions of GHSE (GE2000: 2000 µg/mL) and exosomes from the calli of germinated hemp seeds (E40: 40 μg/mL) in three biochemical categories: genetic modulation in hair follicle dermal papilla stem cells (HFDPSCs), cellular differentiation, and immune system modulation. Upon exposure to dihydrotestosterone (DT), both biomaterials upregulated genes preventing alopecia (Wnt, β-catenin, and TCF) in HFDPSCs and suppressed genes activating alopecia (STAT1, 5α-reductase type 1, IL-15R). Additionally, they suppressed alopecia-related genes (NKG2DL, IL2-Rβ, JAK1, STAT1) in CD8⁺ T cells. Notably, E40 exhibited more pronounced effects compared to GE2000. Consequently, both E40 and GE2000 effectively mitigated DT-induced stress, activating mechanisms promoting hair formation. Given the limited research on alopecia using these materials, their pharmaceutical development promises significant economic and health benefits. Full article

Sensorineural hearing loss (SNHL) is a prevalent and growing global health concern, especially within operational medicine, with limited therapeutic options available. This review article explores the emerging field of in vitro otic organoids as a promising platform for modeling hearing loss and developing novel therapeutic strategies. SNHL primarily results from the irreversible loss or dysfunction of cochlear mechanosensory hair cells (HCs) and spiral ganglion neurons (SGNs), emphasizing the need for innovative solutions. Current interventions offer symptomatic relief but do not address the root causes. Otic organoids, three-dimensional multicellular constructs that mimic the inner ear’s architecture, have shown immense potential in several critical areas. They enable the testing of gene therapies, drug discovery for sensory cell regeneration, and the study of inner ear development and pathology. Unlike traditional animal models, otic organoids closely replicate human inner ear pathophysiology, making them invaluable for translational research. This review discusses methodological advances in otic organoid generation, emphasizing the use of human pluripotent stem cells (hPSCs) to replicate inner ear development. Cellular and molecular characterization efforts have identified key markers and pathways essential for otic organoid development, shedding light on their potential in modeling inner ear disorders. Technological innovations, such as 3D bioprinting and microfluidics, have further enhanced the fidelity of these models. Despite challenges and limitations, including the need for standardized protocols and ethical considerations, otic organoids offer a transformative approach to understanding and treating auditory dysfunctions. As this field matures, it holds the potential to revolutionize the treatment landscape for hearing and balance disorders, moving us closer to personalized medicine for inner ear conditions. Full article

In mammals, hearing loss is irreversible due to the lack of the regenerative capacity of the auditory epithelium. However, stem/progenitor cells in mammalian cochleae may be a therapeutic target for hearing regeneration. The ubiquitin proteasome system plays an important role in cochlear development and maintenance. In this study, we investigated the role of ubiquitin C-terminal hydrolase L1 (UCHL1) in the process of the transdifferentiation of auditory supporting cells (SCs) into hair cells (HCs). The expression of UCHL1 gradually decreased as HCs developed and was restricted to inner pillar cells and third-row Deiters’ cells between P2 and P7, suggesting that UCHL1-expressing cells are similar to the cells with Lgr5-positive progenitors. UCHL1 expression was decreased even under conditions in which supernumerary HCs were generated with a γ-secretase inhibitor and Wnt agonist. Moreover, the inhibition of UCHL1 by LDN-57444 led to an increase in HC numbers. Mechanistically, LDN-57444 increased mTOR complex 1 activity and allowed SCs to transdifferentiate into HCs. The suppression of UCHL1 induces the transdifferentiation of auditory SCs and progenitors into HCs by regulating the mTOR pathway. 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

Grass species have a range of strategies to tolerate soil water restriction, which are linked to the environmental conditions at their site of origin. Climate change enhances the relevance of the functional role of anatomical attributes and their contribution as water stress tolerance factors. Morpho-anatomical traits and adjustments that contribute to drought resistance in Lolium perenne L. (Lp) and Bromus valdivianus Phil. (Bv), a temperate humid grass species, were analysed. The structure of the leaves and pseudostems (stems only in Lp) grown at 20–25% field capacity (FC) (water restriction) and 80–85% FC (control) were evaluated by making paraffin sections. In both species, water restriction reduced the thickness of the leaves and pseudostems, along with the size of the vasculature. Bv had long and dense leaf hairs, small and numerous stomata, and other significant adaptive traits under water stress, including thicker pseudostems (p ≤ 0.001), a greatly thickened bundle sheath wall (p ≤ 0.001) in the pseudostem to ensure water flow, and a thickened cuticle covering on leaf surfaces (p ≤ 0.01) to avoid water loss. Lp vascular bundles developed throughout the stem, and under water restriction the xylem vessel walls were strengthened and lignified. Lp leaves had individual traits of a ribbed/corrugated-shaped upper surface, and the stomata were positioned to maintain relative humidity outside the leaf surface. Water restriction significantly changed the bulliform cell depth in Lp (p ≤ 0.05) that contributed to water loss reduction via the curling leaf blade. This study demonstrated that the two grass species, through different morphological traits, were able to adjust their individual tissues and cells in aboveground parts to reach similar physiological functions to reduce water loss with increased water restriction. These attributes explain how both species enhance persistence and resilience under soil water restriction. Full article

There is substantial experimental and clinical interest in providing effective ways to both prevent and slow the onset of hearing loss. Auditory hair cells, which occur along the basilar membrane of the cochlea, often lose functionality due to age-related biological alterations, as well as from exposure to high decibel sounds affecting a diminished/damaged auditory sensitivity. Hearing loss is also seen to take place due to neuronal degeneration before or following hair cell destruction/loss. A strategy is necessary to protect hair cells and XIII cranial/auditory nerve cells prior to injury and throughout aging. Within this context, it was proposed that cochlea neural stem cells may be protected from such aging and environmental/noise insults via the ingestion of protective dietary supplements. Of particular importance is that these studies typically display a hormetic-like biphasic dose–response pattern that prevents the occurrence of auditory cell damage induced by various model chemical toxins, such as cisplatin. Likewise, the hormetic dose–response also enhances the occurrence of cochlear neural cell viability, proliferation, and differentiation. These findings are particularly important since they confirmed a strong dose dependency of the significant beneficial effects (which is biphasic), whilst having a low-dose beneficial response, whereas extensive exposures may become ineffective and/or potentially harmful. According to hormesis, phytochemicals including polyphenols exhibit biphasic dose–response effects activating low-dose antioxidant signaling pathways, resulting in the upregulation of vitagenes, a group of genes involved in preserving cellular homeostasis during stressful conditions. Modulation of the vitagene network through polyphenols increases cellular resilience mechanisms, thus impacting neurological disorder pathophysiology. Here, we aimed to explore polyphenols targeting the NF-E2-related factor 2 (Nrf2) pathway to neuroprotective and therapeutic strategies that can potentially reduce oxidative stress and inflammation, thus preventing auditory hair cell and XIII cranial/auditory nerve cell degeneration. Furthermore, we explored techniques to enhance their bioavailability and efficacy. Full article

Increasing concerns about hair loss affect people’s quality of life. Recent studies have found that sympathetic nerves play a positive role in regulating hair follicle stem cell activity to promote hair growth. However, no study has investigated sympathetic innervation of transplanted follicles. Rat vibrissa follicles were extracted and implanted under the dorsal skin of BALB/c-nu/nu mice using one of two types of follicles: (1) intact follicles, where transplants included bulbs, and (2) upper follicles, where transplants excluded bulbs. Follicular samples were collected for hematoxylin and eosin staining, immunofluorescence staining for tyrosine hydroxylase (TH, a sympathetic marker) and enzyme-linked immunosorbent assays. At 37 days after implantation in both groups, follicles had entered anagen, with the growth of long hair shafts; tyrosine-hydroxylase-positive nerves were innervating follicles (1.45-fold); and norepinephrine concentrations (2.03-fold) were significantly increased compared to 5 days, but did not return to normal. We demonstrate the survival of intact and upper follicle xenografts and the partial restoration of sympathetic reinnervations of both transplanted follicles. Full article