Cells

30 pages, 35103 KB

Open AccessArticle

TRPA1 and TRPV1 Receptors Protect the Gastric Mucosa from Ethanol-Induced Injury: Evidence from Knockout Mice

by Michal Zalecki, József Kun, Judyta Juranek, Hanna Antushevich, Zsuzsanna Helyes and Erika Pintér

Cells 2026, 15(10), 863; https://doi.org/10.3390/cells15100863 (registering DOI) - 9 May 2026

Abstract

Ethanol disrupts gastric mucosal integrity and induces inflammation. Transient receptor potential ankyrin 1 (TRPA1) and transient receptor potential vanilloid 1 (TRPV1) are receptors expressed in the gastrointestinal tract, but their role in gastric protection against ethanol-induced injury remains unclear. This study investigated the [...] Read more.

Ethanol disrupts gastric mucosal integrity and induces inflammation. Transient receptor potential ankyrin 1 (TRPA1) and transient receptor potential vanilloid 1 (TRPV1) are receptors expressed in the gastrointestinal tract, but their role in gastric protection against ethanol-induced injury remains unclear. This study investigated the contribution of TRPA1 and TRPV1 to gastric responses following ethanol exposure. Wild-type mice and mice lacking TRPA1, TRPV1, or both receptors were subjected to intragastric ethanol administration. Gastric injury was evaluated by macroscopic and histologic analysis. Messenger RNA expression of selected proinflammatory cytokines and receptor transcripts was quantified using quantitative polymerase chain reaction. Receptor localization was examined by double immunofluorescence and confocal microscopy. Ethanol administration induced pronounced gastric mucosal injury in receptor-deficient mice, whereas only minimal changes were observed in wild-type animals. The protective effect was gradational, with weaker protection associated with TRPV1, greater protection with TRPA1, and the strongest protection when both receptors were present, suggesting a combined contribution of both receptors. In wild-type animals, ethanol exposure induced time-dependent changes in receptor expression, suggesting adaptive regulation. Immunofluorescence revealed localization of both receptors in neuronal and non-neuronal structures of the gastric wall. These findings demonstrate the distinct roles of TRPA1 and TRPV1 in protecting the gastric mucosa against ethanol-induced injury. Full article

20 pages, 5294 KB

Open AccessArticle

Experimental Approach to Moyamoya Angiopathy: Insights into Vascular Cell Crosstalk

by Gemma Gorla, Antonella Potenza, Tatiana Carrozzini, Giuliana Pollaci, Elisabetta Pasella, Erika Salvi, Isabella Canavero, Nicola Rifino, Paolo Ferroli, Marco Paolo Schiariti, Francesco Restelli, Francesco Acerbi, Anna Bersano and Laura Gatti

Cells 2026, 15(10), 862; https://doi.org/10.3390/cells15100862 (registering DOI) - 9 May 2026

Abstract

Background: The pathophysiological mechanisms of Moyamoya angiopathy (MA) are still largely unknown, although a dysfunctional vasculogenesis has been hypothesized to contribute to it. The association between this rare cerebrovascular condition and variants of Ring Finger Protein 213 (RNF213) strengthens the role of genetic [...] Read more.

Background: The pathophysiological mechanisms of Moyamoya angiopathy (MA) are still largely unknown, although a dysfunctional vasculogenesis has been hypothesized to contribute to it. The association between this rare cerebrovascular condition and variants of Ring Finger Protein 213 (RNF213) strengthens the role of genetic factors in MA pathogenesis. Methods: To investigate the molecular mechanisms of MA, we carried out RNA interference (RNAi) targeting RNF213 in human endothelial cells (ECs) and vascular smooth muscle cells (VSMCs). The combined effect of RNAi and/or hypoxia on expression of key angiogenic factors was analyzed through qRT-PCR and Western blot. Functional assays were performed to characterize the impact of RNAi on vasculogenesis. Gene-expression arrays were performed on vessel walls of MA patients and controls. Results: RNF213-RNAi impaired angiogenic capability in ECs, whereas the simultaneous silencing of RNF213 and its phosphatase PTP1B restored angiogenesis function in ECs but worsened it in VSMCs. Angiogenic factor expression appeared to be modulated in ECs by the combined effects of RNAi and/or hypoxia, and in pathological vessels of MA patients as compared with controls. Conclusions: Our findings contribute to associating the relevance of RNF213 in MA cellular models and highlight the importance of EC-VSMC crosstalk for vascular integrity. Additionally, the study could lay the foundations for improving experimental models of MA pathophysiology. Full article

(This article belongs to the Special Issue Novel Insights into Endothelial Cells in Vascular Disease)

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29 pages, 2231 KB

Open AccessReview

Wavelength-Dependent Modulation of Mesenchymal Stem Cell Fate: A Systems Biology Framework for Tissue Repair and Regenerative Medicine

by Baptiste Amouroux, Kimia Motlagh Asghari, Morgane De Sousa, Virginie Gueguen, Cédric Chauvierre, Abolfazl Barzegari and Graciela Pavon-Djavid

Cells 2026, 15(10), 861; https://doi.org/10.3390/cells15100861 - 8 May 2026

Abstract

Mesenchymal stem cells (MSCs) are central effectors in regenerative medicine, yet their clinical translation is hindered by inconsistent therapeutic outcomes and a lack of standardized light-delivery protocols. This review addresses an underexplored dimension of photobiomodulation (PBM): the divergent, wavelength-dependent signaling programs triggered in [...] Read more.

Mesenchymal stem cells (MSCs) are central effectors in regenerative medicine, yet their clinical translation is hindered by inconsistent therapeutic outcomes and a lack of standardized light-delivery protocols. This review addresses an underexplored dimension of photobiomodulation (PBM): the divergent, wavelength-dependent signaling programs triggered in MSCs by red/near-infrared (NIR) versus blue light. By integrating biophysical principles of light delivery with a systems biology analysis of protein–protein interaction networks (STRING/GO), we delineate a “Dual Photonic Programming” framework. Red/NIR light (600–1100 nm) targets mitochondrial cytochrome c oxidase, activating a bioenergetic-anabolic program centered on PI3K/Akt/mTOR and Wnt/β-catenin—pathways essential for structural tissue repair. Blue light (400–500 nm) engages cytosolic flavins to drive a secretory-paracrine program that modulates vesicle trafficking and immunomodulatory cargo release. We further examine the dosimetric paradox, demonstrating how culture-environment optics and the Arndt–Schultz biphasic law govern the transition from regenerative stimulation to inhibitory oxidative stress. By tailoring photonic parameters to the MSC’s anatomical origin and metabolic baseline, PBM can serve as a high-fidelity bio-switch for orchestrated tissue repair, providing a mechanistic roadmap for standardized regenerative therapies. Full article

(This article belongs to the Special Issue Stem Cells and Beyond: Innovations in Tissue Repair and Regeneration)

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20 pages, 4879 KB

Open AccessArticle

CXCL14 Inhibits Colon Cancer Progression by Modulating Tumor Cell Invasion and Immune Microenvironment

by Yinjie Zhang, Siyi Wang, Yuchen Niu, Yanjing Wang, Buyong Ma and Jingjing Li

Cells 2026, 15(10), 860; https://doi.org/10.3390/cells15100860 - 8 May 2026

Abstract

CXCL14 is a highly conserved chemokine with potential roles in tumor progression and immune modulation. This study investigates the functional impact of CXCL14 on colon cancer by exploring its effects on tumor cell behavior and the immune microenvironment. We generated stable cell lines [...] Read more.

CXCL14 is a highly conserved chemokine with potential roles in tumor progression and immune modulation. This study investigates the functional impact of CXCL14 on colon cancer by exploring its effects on tumor cell behavior and the immune microenvironment. We generated stable cell lines overexpressing CXCL14 in mouse MC38 and CT26 cells and human HCT15 colon cancer cells, and used these models to assess tumor growth, invasion, and immune cell infiltration. Our results demonstrate that CXCL14 suppresses colon cancer cell proliferation, migration, and metastasis. In vitro, CXCL14 inhibited the expression of matrix metalloproteinases (MMPs), key regulators of epithelial–mesenchymal transition (EMT), suggesting a role in promoting mesenchymal–epithelial transition (MET). Additionally, in vivo studies using a subcutaneous tumor model showed that CXCL14 not only suppressed tumor growth but also enhanced the infiltration of immune cells, including NK cells, dendritic cells (DCs), and T cells, converting the tumor microenvironment from a “cold” to a “hot” phenotype. RNA sequencing and pathway analyses revealed that CXCL14 regulates the expression of genes associated with angiogenesis, immune response, and cell signaling, particularly through the MAPK pathway. Furthermore, CXCL14’s influence on tumor progression was confirmed in a spleen-to-liver metastasis model, where its overexpression reduced metastatic spread. In conclusion, CXCL14 inhibits colon cancer progression by modulating both tumor cell behavior and the immune landscape, making it a promising candidate for targeted immunotherapy. Our findings highlight CXCL14’s potential to enhance anti-tumor immunity and provide new insights into its therapeutic applications in colon cancer. Full article

(This article belongs to the Collection Trends and Advances in Tumor Immunology)

22 pages, 7385 KB

Open AccessArticle

An Innovative Bioengineering Approach to Investigate the Response of Melanin-Rich Cells to Intense Pulsed Light (IPL)

by Kirsty Goncalves, Kous Shah, Victoria Maltman, Yuwen Chen, Nicole Barrett, Georgia Abraham, Ilaria Ambrogio, Teresa DiColandrea, John Snowball and Stefan Przyborski

Cells 2026, 15(10), 859; https://doi.org/10.3390/cells15100859 - 8 May 2026

Abstract

Light-based therapies are becoming increasingly = more mainstream, not only within the medical science space, but also within the fields of cosmetic dermatology and personal grooming. Intense Pulsed Light (IPL) harnesses the ability of the natural chromophore–melanin to absorb light energy, which is [...] Read more.

Light-based therapies are becoming increasingly = more mainstream, not only within the medical science space, but also within the fields of cosmetic dermatology and personal grooming. Intense Pulsed Light (IPL) harnesses the ability of the natural chromophore–melanin to absorb light energy, which is translated into heat energy and consequently results in targeted thermolysis of cells rich in melanin. This mechanistic pathway lends itself to a wide range of applications, including long-term hair removal, skin rejuvenation, the treatment of unwanted pigmentation, and the treatment of ophthalmic conditions. The development of home use devices (HUDs) for the delivery of IPL-mediated hair removal has facilitated the self-administration of photothermal treatments and reduced reliance on clinical settings. In this study, we demonstrate a pioneering approach to model aspects of IPL-induced thermal induction and selective thermolysis in a complex human skin tissue equivalent. Our approach utilised a deactivated HUD with disabled safety features that allowed for the exposure of tissue constructs to high-fluence IPL. We demonstrate an increase in biomarkers consistent with increased cellular temperature, induction of apoptosis, and increased pro-inflammatory cytokine release following extreme treatment regimens, all of which correlate with an increased fluence and/or increased number of IPL pulses delivered. This method allowed for the identification of cellular events evoked by increasing fluence and extreme-exposure regimes. Full article

(This article belongs to the Special Issue Cutaneous Regeneration and Tissue Engineering: From Hair Follicle Regeneration to Skin Restoration)

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20 pages, 3193 KB

Open AccessReview

Exercise-Induced Hypoalgesia: Cellular and Molecular Mechanisms Linking Pain Modulation and Stress Regulation—A Narrative Review

by Pavle Gajic, Ivana Kovac, Graham Lubinsky and Nebojsa Nick Knezevic

Cells 2026, 15(10), 858; https://doi.org/10.3390/cells15100858 - 8 May 2026

Abstract

Exercise-induced hypoalgesia (EIH) illustrates how physical activity can reshape the biology of pain while simultaneously influencing the systems that regulate stress. Acute and repeated exercise can reduce pain sensitivity in healthy individuals and in some chronic pain populations, yet the magnitude and consistency [...] Read more.

Exercise-induced hypoalgesia (EIH) illustrates how physical activity can reshape the biology of pain while simultaneously influencing the systems that regulate stress. Acute and repeated exercise can reduce pain sensitivity in healthy individuals and in some chronic pain populations, yet the magnitude and consistency of these effects vary substantially across individuals, diagnoses, and exercise protocols. This variability suggests that EIH is not a uniform response, but an adaptive multisystem process shaped by neural, immune, endocrine, metabolic, musculoskeletal, and psychosocial factors. This narrative review synthesizes evidence linking pain modulation and stress regulation across biological scales. Exercise engages descending pain modulatory circuits involving the periaqueductal gray, rostral ventromedial medulla, and spinal dorsal horn, while also influencing endogenous opioid, endocannabinoid, serotonergic, and noradrenergic signaling. These pathways are relevant not only to nociceptive inhibition, but also to affective regulation, hypothalamic–pituitary–adrenal axis activity, autonomic balance, and perceived stress. In parallel, exercise-related neuroimmune changes, including modulation of microglial activity, cytokine signaling, and myokine release from skeletal muscle, may connect peripheral metabolic activity with central mechanisms of pain and stress adaptation. Importantly, the evidence supporting these mechanisms differs in strength: some findings derive from human experimental and clinical studies, whereas others are supported mainly by preclinical or translational research. By distinguishing direct evidence from mechanistic inference, this review highlights how exercise may support hypoalgesia, stress resilience, and functional recovery, while also emphasizing the need for biomarker-informed, personalized exercise strategies in chronic pain management. Full article

(This article belongs to the Special Issue Molecular Mechanisms Underlying Inflammatory Pain)

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19 pages, 8630 KB

Open AccessArticle

Single-Cell Transcriptomic Profiling Uncovers a Metastasis-Associated MUCL3⁺ Signet-Ring Cell Subpopulation in Gastric Cancer

by Jie Zhang, Yinping Wang, Ting Yuan, Wenguang Wu, Xuechuan Li, Zhaoyuan Hou, Maolan Li and Yingbin Liu

Cells 2026, 15(10), 857; https://doi.org/10.3390/cells15100857 - 8 May 2026

Abstract

Background: Gastric signet-ring cell carcinoma (GSRCC) is an aggressive gastric cancer subtype with abundant mucin production and high metastatic propensity. However, scarcity of specific biomarkers has impeded clinical diagnosis and mechanistic research. This study systematically compares GSRCC and gastric adenocarcinoma (AC) to [...] Read more.

Background: Gastric signet-ring cell carcinoma (GSRCC) is an aggressive gastric cancer subtype with abundant mucin production and high metastatic propensity. However, scarcity of specific biomarkers has impeded clinical diagnosis and mechanistic research. This study systematically compares GSRCC and gastric adenocarcinoma (AC) to identify biomarkers and elucidate molecular basis of GSRCC’s aggressive behavior. Methods: We performed single-cell RNA sequencing (scRNA-seq) on surgically resected primary GC tissues, validating our findings using public datasets and functional experiments. Results: We identified expansion of a mucin-secreting epithelial subcluster (Mucous_muc5ac) in GSRCC, characterized by high MUC5AC, TFF1, and other prognosis-associated genes. Within this population, a MUCL3⁺ subpopulation (Cluster 1) spatially corresponded with classic signet-ring morphology, validating MUCL3 as a specific marker for these cells. Multi-omics analysis revealed that MUCL3⁺ signet-ring cells exhibit genomic instability, dedifferentiation, and enrichment of TNF-α/NF-κB, TGF-β/EMT, and hypoxia pathways, with elevated metastasis/angiogenesis gene scores and high TFF1 expression. Functional validation confirmed that TFF1 was associated with increased gastric cancer cell migration. Conclusions: Our study characterizes the MUCL3⁺ signet-ring cell subpopulation, highlighting the diagnostic utility of MUCL3 and suggesting TFF1 as a candidate for further investigation. These findings establish a foundation for advancing precision diagnosis and mechanistic understanding of GSRCC. Full article

(This article belongs to the Special Issue Gastrointestinal Cancers: Research, Novel Diagnostic and Treatment Methods)

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1 pages, 138 KB

Open AccessCorrection

Correction: Burla et al. Reduced CHMP7 Expression Compromises Telomere Integrity in Mammalian Cells. Cells 2026, 15, 256

by Romina Burla, Mattia La Torre, Klizia Maccaroni, Stefano Tacconi, Marco Fidaleo, Luciana Dini and Isabella Saggio

Cells 2026, 15(10), 856; https://doi.org/10.3390/cells15100856 - 8 May 2026

Abstract

In the original publication [...] Full article

49 pages, 8272 KB

Open AccessReview

The Role of Oral Pathobionts’ Outer Membrane Vesicles in Cancer Pathology and Therapeutic Development

by Sara Hadjigol, Bansari A. Shah, Negar Yazdani and Neil M. O’Brien-Simpson

Cells 2026, 15(10), 855; https://doi.org/10.3390/cells15100855 - 8 May 2026

Abstract

Cancer remains one of the leading causes of mortality worldwide, with increasing recognition of the host microbiome as a modifiable contributor to tumour initiation and progression. Among microbial mediators, outer membrane vesicles (OMVs) derived from Gram-negative oral pathobionts have emerged as critical effectors [...] Read more.

Cancer remains one of the leading causes of mortality worldwide, with increasing recognition of the host microbiome as a modifiable contributor to tumour initiation and progression. Among microbial mediators, outer membrane vesicles (OMVs) derived from Gram-negative oral pathobionts have emerged as critical effectors of host–microbe interactions. These nanoscale vesicles function as delivery systems for a diverse range of bioactive cargo, including virulence factors, lipopolysaccharides, proteins, and nucleic acids, enabling both local and systemic modulation of host cellular processes. Emerging evidence suggests that OMVs produced by oral pathobionts, particularly Porphyromonas gingivalis and Fusobacterium nucleatum, are associated with tumour-promoting inflammation, immune dysregulation, epithelial transformation, and metastatic progression. Mechanistically, OMVs have been shown to activate key signalling pathways, disrupt mitochondrial function, induce oxidative stress, and reprogram the tumour microenvironment in ways that favour cancer cell survival and immune evasion. In addition, OMV-mediated modulation of host responses has been linked to resistance to anticancer therapies. In this review, we synthesize current evidence on the role of oral pathobionts’ OMVs in cancer biology, with a focus on their contributions to tumour initiation, progression, and metastasis. We further discuss emerging clinical associations, the potential of OMV-derived components as diagnostic biomarkers, and the growing interest in engineered OMVs as platforms for therapeutic intervention. Finally, we highlight key challenges and knowledge gaps that must be addressed to advance the translational application of OMV-based strategies in oncology. Overall, OMVs represent a promising but still evolving link between the oral microbiome and cancer, offering new insights into disease mechanisms and potential avenues for diagnosis and therapy. Full article

(This article belongs to the Special Issue Extracellular Vesicles in Disease Pathogenesis, Therapeutics and Biomarker Discovery)

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17 pages, 6467 KB

Open AccessArticle

Limonoid 7-Deacetoxy-7-Oxogedunin (CG-1) Attenuates RANKL-Induced Osteoclastogenesis via Inhibiting PI3K/Akt-NFATc1 Axis

by Atsushi Koike and Ko Fujimori

Cells 2026, 15(10), 854; https://doi.org/10.3390/cells15100854 - 7 May 2026

Abstract

Excessive bone resorption by osteoclasts causes pathological bone loss in diseases such as osteoporosis. 7-Deacetoxy-7-oxogedunin (CG-1), a limonoid isolated from Carapa guianensis (Meliaceae), exhibits various biological activities. Here, we examined the anti-osteoclastogenic effect of CG-1 and its underlying mechanism in receptor activator of [...] Read more.

Excessive bone resorption by osteoclasts causes pathological bone loss in diseases such as osteoporosis. 7-Deacetoxy-7-oxogedunin (CG-1), a limonoid isolated from Carapa guianensis (Meliaceae), exhibits various biological activities. Here, we examined the anti-osteoclastogenic effect of CG-1 and its underlying mechanism in receptor activator of NF-κB ligand (RANKL)-induced osteoclast differentiation of RAW264.7 cells. CG-1 inhibited the formation of tartrate-resistant acid phosphatase-positive multinucleated cells and decreased the expression of osteoclastogenesis-related genes. When CG-1 was added to the culture during the first 3 days of the 5-day-osteoclastogenesis period, the expression levels of the osteoclastogenesis-related genes (Nfatc1, Acp5, Src, Ctsk, and Mmp9) were decreased, as was observed when CG-1 was added continuously for 5 days. Furthermore, CG-1 lowered RANKL-induced Akt phosphorylation, which is similar to the results seen with the PI3K inhibitor, LY294002. Moreover, CG-1 and LY294002 suppressed the RANKL-induced expression of NFATc1, the master transcription factor for regulating terminal differentiation into osteoclasts. These results suggest that CG-1 attenuated RANKL-induced osteoclastogenesis by inhibiting the PI3K/Akt-NFATc1 axis during the early stage of osteoclast differentiation. Thus, CG-1 has the potential to suppress osteoclast-mediated bone resorption. Full article

(This article belongs to the Section Cellular Metabolism)

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21 pages, 4425 KB

Open AccessArticle

Mapping Genetic Modifiers of Polyp Formation in Smad4-Deficient Juvenile Polyposis Using the Collaborative Cross Mouse Population

by Osayd Zohud, Kreem Midlej, Iqbal M. Lone, Aysar Nashef, Imad Abu-Elnaaj and Fuad A. Iraqi

Cells 2026, 15(10), 853; https://doi.org/10.3390/cells15100853 - 7 May 2026

Abstract

Juvenile Polyposis Syndrome (JPS) is an autosomal dominant disorder characterized by multiple gastrointestinal polyps and an increased risk of cancer, most commonly associated with mutations in the tumor suppressor gene Smad4. However, substantial phenotypic variability exists among individuals carrying identical mutations, suggesting [...] Read more.

Juvenile Polyposis Syndrome (JPS) is an autosomal dominant disorder characterized by multiple gastrointestinal polyps and an increased risk of cancer, most commonly associated with mutations in the tumor suppressor gene Smad4. However, substantial phenotypic variability exists among individuals carrying identical mutations, suggesting the presence of genetic modifiers. In this study, we used the genetically diverse Collaborative Cross (CC) mouse population crossed with Smad4 knockout mice to identify loci influencing intestinal polyp development. A cohort of 260 F1 mice derived from 14 CC lines was assessed for polyp number and size across intestinal segments. Quantitative trait locus (QTL) mapping revealed several significant loci, including regions on chromosomes 16, 14, and 12, which were designated Ipsl1, Ipsl2, and Ipsl3 for Intestinal Polyposis Susceptibility locus (Ipsl), respectively, in the full population, as well as additional sex-specific loci in male and female cohorts. Pathway enrichment analysis of genes within these regions highlighted functional associations with immune signaling, ubiquitin–proteasome degradation, and metabolic regulation. Candidate genes, including STAM2, PSMD6, NAMPT, and CACNB4, emerged as potential modifiers of polyp susceptibility. These findings highlight the complex genetic architecture underlying JPS phenotypes and provide candidate loci for future functional and translational investigations. Full article

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32 pages, 3991 KB

Open AccessReview

Gene Editing Strategies for Duchenne Muscular Dystrophy: From Molecular Mechanisms to Clinical Translation

by Ayesha Siddika, Joël Rousseau, Félix Veillette, Camille Bouchard, Yaoyao Lu and Jacques P. Tremblay

Cells 2026, 15(10), 852; https://doi.org/10.3390/cells15100852 - 7 May 2026

Abstract

Duchenne muscular dystrophy (DMD) remains a major challenge in genetic medicine due to the difficulty of achieving durable, body-wide restoration of dystrophin in post-mitotic muscle tissues. Although current therapies—including exon skipping and micro-dystrophin gene replacement—have demonstrated clinical feasibility, their benefits are limited by [...] Read more.

Duchenne muscular dystrophy (DMD) remains a major challenge in genetic medicine due to the difficulty of achieving durable, body-wide restoration of dystrophin in post-mitotic muscle tissues. Although current therapies—including exon skipping and micro-dystrophin gene replacement—have demonstrated clinical feasibility, their benefits are limited by incomplete efficacy, mutation specificity, and the need for repeated or high-dose interventions. These limitations highlight the need for strategies capable of directly and permanently correcting the underlying genetic defect. Recent advances in genome editing have positioned CRISPR-based technologies as promising candidates for this objective. Rather than functioning as a single approach, gene-editing platforms encompass a spectrum of strategies—including exon deletion, exon reframing, base editing, and prime editing—each with distinct advantages depending on the mutational context. In particular, the emergence of precision editing tools has enabled controlled nucleotide-level modifications, expanding the range of correctable mutations while reducing reliance on double-strand DNA breaks. In this review, we adopt a comparative and translational perspective to evaluate gene-editing strategies for DMD. We examine how different approaches align with specific mutation types, summarize key findings from preclinical studies, and analyze the major barriers to clinical implementation, including delivery efficiency, immune responses, editing durability, and genomic safety. We further discuss emerging innovations in editing technologies and delivery systems that aim to address these limitations. Collectively, this work reframes gene editing as a decision-oriented and application-driven therapeutic framework. Continued integration of advances in genome engineering, delivery platforms, and muscle biology will be essential to translate these technologies into safe, effective, and durable treatments capable of altering the clinical trajectory of DMD. Full article

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18 pages, 2579 KB

Open AccessArticle

Voltage-Gated Sodium Channels Regulate the Migration Potential of Human Endometrial Mesenchymal Stem/Stromal Cells in 2D and 3D Culture

by Margarita Shamatova, Mariia Shorokhova, Irina Vassilieva, Vladislav Chubinskiy-Nadezhdin and Anastasia Sudarikova

Cells 2026, 15(10), 851; https://doi.org/10.3390/cells15100851 - 7 May 2026

Abstract

Human endometrial mesenchymal stem/stromal cells (eMSCs) are widely used in laboratories and clinical applications to study various aspects of tissue engineering and regenerative medicine. Three-dimensional (3D) cultivated MSCs have a higher therapeutic efficacy compared to 2D culture. Ion channels are involved in maintaining [...] Read more.

Human endometrial mesenchymal stem/stromal cells (eMSCs) are widely used in laboratories and clinical applications to study various aspects of tissue engineering and regenerative medicine. Three-dimensional (3D) cultivated MSCs have a higher therapeutic efficacy compared to 2D culture. Ion channels are involved in maintaining many physiological cell functions, including proliferation, differentiation, apoptosis, and migration. This study describes the functional expression of voltage-gated sodium channels (NaV) in eMSCs and the role of these channels in cell migration. Using RT-PCR analysis and immunofluorescent microscopy, we identified the expression of almost all pore-forming alpha (NaV 1.1, 1.2, 1.4–1.9) and channel-modulating beta-NaV subunits (except beta2) in eMSCs. In the whole-cell patch-clamp configuration, channels activated by membrane depolarization of eMSC were detected. The channels were blocked by the selective NaV antagonist TTX in nanomolar concentrations. The NaV agonist veratridine at a concentration of less than 40 μM inhibited voltage-gated sodium currents, while 100 μM and above prevented channel inactivation. The wound healing assay showed that both TTX (10 μM) and veratridine (100 μM) reduced the migration properties (the wound healing rate) of eMSCs cultivated in 2D conditions compared to the control. An opposite effect by both agents was shown on the motility of eMSCs cultivated in 3D conditions, increasing the cell spreading rate from spheroids. Our data suggest that NaV channels are expressed in human eMSCs and play an important role in the regulation of stem cell migration; this regulatory mechanism significantly depends on the culture conditions of MSCs. Full article

(This article belongs to the Special Issue Mesenchymal Stem Cells in Cell Therapy, Regenerative Medicine, and Tissue Engineering)

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21 pages, 2238 KB

Open AccessReview

Overcoming Biological Barriers and Drug Resistance Through Next-Generation Nanotherapeutic Delivery in Gastric Cancer

by Md Ataur Rahman, Maroua Jalouli, Abdel Halim Harrath, Jinwon Choi, Min Choi, Hyo Jeong Kim, Sohyun Park, Bum-Sang Shim, Amama Rani and Bonglee Kim

Cells 2026, 15(10), 850; https://doi.org/10.3390/cells15100850 - 7 May 2026

Abstract

Gastric cancer (GC) is one of the most aggressive malignancies with a dismal prognosis, late diagnosis, and limited therapy efficacy. Biologically, GC is associated with multiple barriers to therapeutic response including gastric mucosal layer, acidic tumor microenvironment (TME), high accumulation of extracellular matrix [...] Read more.

Gastric cancer (GC) is one of the most aggressive malignancies with a dismal prognosis, late diagnosis, and limited therapy efficacy. Biologically, GC is associated with multiple barriers to therapeutic response including gastric mucosal layer, acidic tumor microenvironment (TME), high accumulation of extracellular matrix (ECM) components, and limited penetration depth of anticancer drugs into tumor tissue. Furthermore, inherent or acquired drug resistance associated with drug efflux transporters, deregulated autophagy, tumor heterogeneity, and cell survival pathways severely compromise treatment response. Nanotechnology has been widely used to develop next-generation nanotherapeutic delivery systems to overcome these biological barriers. Currently available nanoplatforms such as liposomes, polymeric nanoparticles, dendrimers, and inorganic nanocarriers have improved drug loading capacity, aqueous solubility, circulation time stability, tumor-targeted delivery, and sustained release of chemotherapeutics. Smart and stimuli-responsive nanocarriers can also take advantage of pathological hallmarks of tumors including low pH, redox potential, and overexpressed enzymes for enhanced selective delivery to the tumor site. Nanotherapeutics have also shown promise for co-delivery of multiple therapeutic agents to overcome drug resistance, manipulation of TME, and suppression of autophagy and apoptosis signaling pathways associated with drug resistance. This review discusses recent advances in nanotherapeutics for GC including approaches to overcome biological barriers and drug resistance and highlights translational gaps for clinical development. Full article

(This article belongs to the Collection Gastrointestinal Disease: From Molecular and Cellular Mechanisms to Novel Therapeutics)

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