Cells

15 pages, 801 KB

Open AccessReview

H19/miR-675 Axis Promotes Cancer Metastasis by Orchestrating EMT and MET Processes

by Kekely Klouyovo, Xuefen Le Bourhis and Éric Adriaenssens

Cells 2026, 15(8), 658; https://doi.org/10.3390/cells15080658 - 8 Apr 2026

Despite substantial advances in our understanding of cancer metastasis, it remains the leading cause of mortality among cancer patients. Elucidating the molecular mechanisms that drive metastatic progression is expected to facilitate the development of more effective therapeutic strategies. Among the numerous candidates, the [...] Read more.

Despite substantial advances in our understanding of cancer metastasis, it remains the leading cause of mortality among cancer patients. Elucidating the molecular mechanisms that drive metastatic progression is expected to facilitate the development of more effective therapeutic strategies. Among the numerous candidates, the long non-coding RNA H19 and its derivative miR-675 have been increasingly recognized as key regulators of metastatic dissemination in cancers of diverse tissue origins. In this review, we provide an up-to-date overview of the H19/miR-675 axis in metastatic progression, with particular emphasis on its involvement in the dynamic and complementary processes of epithelial–mesenchymal transition (EMT) and mesenchymal–epithelial transition (MET). We also highlight the opportunity to consider the H19/miR-675 axis as promising biomarkers and potential therapeutic targets. Full article

34 pages, 1874 KB

Open AccessReview

Immunosenescence and Inflammaging as Drivers of Neurodegeneration: Cellular Mechanisms, Neuroimmune Crosstalk, and Therapeutic Implications

by Gianmarco Bertoni, Sara Ristori and Daniela Monti

Cells 2026, 15(8), 657; https://doi.org/10.3390/cells15080657 - 8 Apr 2026

Abstract

Aging is accompanied by profound alterations in immune function, termed immunosenescence, and by a chronic, low-grade inflammatory state known as inflammaging. These processes are increasingly recognized as central drivers of age-related neurodegenerative diseases, including Alzheimer’s Disease, Parkinson’s Disease, Amyotrophic Lateral Sclerosis and Multiple [...] Read more.

Aging is accompanied by profound alterations in immune function, termed immunosenescence, and by a chronic, low-grade inflammatory state known as inflammaging. These processes are increasingly recognized as central drivers of age-related neurodegenerative diseases, including Alzheimer’s Disease, Parkinson’s Disease, Amyotrophic Lateral Sclerosis and Multiple Sclerosis. In the central nervous system, senescent microglia and astrocytes lose their homeostatic and neuroprotective functions, while systemic immune aging and blood–brain barrier dysfunction further amplify neuroinflammation and impair protein aggregate clearance. This sustained pro-inflammatory environment promotes synaptic dysfunction, neuronal loss and cognitive decline. Here, we synthesize current knowledge of the mechanistic links among immunosenescence, inflammaging, and neurodegeneration, highlighting innate and adaptive immune dysregulation, mitochondrial impairment, and failed resolution pathways. We further discuss emerging therapeutic strategies, including senolytics, immunoceuticals, microbiome-based interventions and advanced drug delivery systems, aimed at restoring immune homeostasis and enhancing brain resilience. By integrating mechanistic and translational insights, this review provides a framework for developing novel interventions to target immune aging in neurodegenerative diseases. Full article

(This article belongs to the Special Issue Targeting Immune Dysfunction in Aging and Age-Related Diseases)

► Show Figures

Graphical abstract

28 pages, 625 KB

Open AccessReview

Stem Cells and Their Derivatives in Cardiac Fibrosis Therapy: Challenges and Perspectives

by Adrian Piwowar, Zuzanna Zolbach, Julia Rydzek, Natalia Skonieczna, Katarzyna Rojek, Mateusz Żołyniak, Julia Soczyńska and Sławomir Woźniak

Cells 2026, 15(8), 656; https://doi.org/10.3390/cells15080656 - 8 Apr 2026

Abstract

Cardiac fibrosis is a pathology induced by various conditions, such as myocardial infarction, or certain cardiomyopathies, and represents one of the most prevalent cardiac abnormalities. This process, defined as the excessive accumulation of extracellular matrix within damaged cardiac tissue, leads to significant complications, [...] Read more.

Cardiac fibrosis is a pathology induced by various conditions, such as myocardial infarction, or certain cardiomyopathies, and represents one of the most prevalent cardiac abnormalities. This process, defined as the excessive accumulation of extracellular matrix within damaged cardiac tissue, leads to significant complications, including impaired systolic and diastolic function as well as arrhythmias. Conventional therapies focus primarily on slowing down the progression of fibrosis. Recently, there has been a growing research interest in therapies based on stem cells and their derivatives, which hold the potential to greater decrease formation and area of fibrosis. In this review, we aim to systematise the most recent data regarding the application of these approaches. We focus on describing the types of cells employed, methods of their implementation, and strategies for optimising these processes. Particular attention is given to exosomes due to the reports highlighting their use as innovative and potentially effective tools in the treatment of cardiac diseases. Full article

(This article belongs to the Section Cells of the Cardiovascular System)

► Show Figures

Figure 1

19 pages, 15696 KB

Open AccessArticle

From Phage Display to Yeast Secretion: Developing Fc-Fused Nanobodies Against Influenza Virus

by Mei Wang, Shujun Li, Yong Li, Xiaomei Xia, Yan Zhang, Ning Cao, Yuanfang Li, Yijia Liu, Sheng Zhang, Lilin Zhang and Jinhai Huang

Cells 2026, 15(8), 655; https://doi.org/10.3390/cells15080655 - 8 Apr 2026

Abstract

Avian influenza infections cause substantial economic losses in the poultry industry and raise public health concerns due to viral adaptation and cross-species transmission. The frequent antigenic drift of influenza viruses further complicates the prevention and treatment of avian respiratory infections. In this study, [...] Read more.

Avian influenza infections cause substantial economic losses in the poultry industry and raise public health concerns due to viral adaptation and cross-species transmission. The frequent antigenic drift of influenza viruses further complicates the prevention and treatment of avian respiratory infections. In this study, we generated high-affinity heavy-chain variable domain (VHH) nanobodies from naïve alpaca/camelid VHH libraries using phage display combined with H9N2 influenza A virus (IAV)-infected Madin-Darby Canine Kidney (MDCK) cells. Based on binding affinity and neutralization potential, we identified seven hemagglutinin (HA)-specific and two neuraminidase (NA)-specific VHHs. Molecular docking predicted the interaction sites of HA-specific VHHs (L1-2, L1-4, A5) and NA-specific VHHs (L1-3, L2-2), providing mechanistic insights. Notably, the three HA-specific VHHs (L1-2, L1-4, A5) showed cross-reactivity to representative HA subtypes (H1, H3, and influenza B), indicating recognition of conserved epitopes across divergent influenza strains. For the first time, these camelid nanobodies were fused to the chicken IgY Fc domain, and the expression cassette was integrated into the Saccharomyces cerevisiae genome, achieving a secretion yield of 15–20 mg/L of VHH-Fc antibodies. Experimental validation confirmed that the three HA-specific VHHs-Fc constructs effectively blocked viral infection, while the two NA-specific VHH-Fc constructs (L1-3, L2-2) inhibited NA activity, demonstrating the functional efficacy of the yeast-secreted VHH–IgY Fc platform. This novel IgY Fc fusion approach offers a scalable platform with enhanced stability, extended circulation potential, and applicability in poultry. Full article

(This article belongs to the Topic Advances in Vaccines and Antimicrobial Therapy—2nd Edition)

► Show Figures

Graphical abstract

23 pages, 919 KB

Open AccessArticle

Fixed-Bed Bioreactor Culture Enhances Yield and Reparative Properties of hTERT Mesenchymal Stem Cell Extracellular Vesicles

by Zachary Cuba, Lenny Godinho, Sujata Choudhury, Kajal Patil, Anastasia Williams, Weidong Zhou, Marissa Howard, Surya P. Aryal, Kevin A. Clayton, David A. Routenberg, Lance A. Liotta, Heather Couch, Fatah Kashanchi and Heather Branscome

Cells 2026, 15(7), 654; https://doi.org/10.3390/cells15070654 - 7 Apr 2026

Abstract

Mesenchymal stem cells (MSCs) are multipotent cells that have the ability to mediate cellular repair through a combination of soluble paracrine factors, as well as bioactive cargo packaged within extracellular vesicles (EVs). Although MSC-derived EVs have been widely investigated for their regenerative potential, [...] Read more.

Mesenchymal stem cells (MSCs) are multipotent cells that have the ability to mediate cellular repair through a combination of soluble paracrine factors, as well as bioactive cargo packaged within extracellular vesicles (EVs). Although MSC-derived EVs have been widely investigated for their regenerative potential, progress toward translational evaluation has been limited in part by challenges in scalable and reproducible manufacturing. We recently reported that human telomerase reverse transcriptase (hTERT)-immortalized MSCs reproducibly produce EVs that retain key characteristics of EVs derived from primary MSCs. Building on this work, three-dimensional (3D) culture systems have emerged as promising platforms for large-scale manufacturing. In this study, we compared the yield, molecular composition, and functional activity of EVs produced from hTERT-immortalized MSCs cultured in either a fixed-bed bioreactor or conventional two-dimensional (2D) flasks. Our data demonstrate that bioreactor culture results in increased EV yield as compared to an equivalent production from 2D cultures. Molecular analyses indicated that bioreactor-derived EVs were associated with a broader spectrum of cargo and were enriched with molecules that may contribute to enhanced reparative function. Importantly, bioreactor-derived EVs also exerted a more pronounced effect in cellular repair assays in vitro. Collectively, these results highlight the potential of fixed-bed bioreactors as scalable platforms for EV production, offering higher yields while preserving molecular composition and functional activity. This approach represents an important step toward achieving the reproducible, high-quality EV production required for research and future translational applications. Full article

36 pages, 1501 KB

Open AccessReview

Messing with Signal 1: How Perturbed MHC Class I Antigen Presentation Contributes to Cancer

by Myriam Lawand, Salman Al Rayess, Rawad Jaber and Peter van Endert

Cells 2026, 15(7), 653; https://doi.org/10.3390/cells15070653 - 7 Apr 2026

Abstract

The antigen presentation machinery processes proteins for presentation to T cells, thereby controlling activation of the adaptive cellular immune response. Perturbation of this machinery has been linked to the development of various diseases. This review describes the function of the Major Histocompatibility Complex [...] Read more.

The antigen presentation machinery processes proteins for presentation to T cells, thereby controlling activation of the adaptive cellular immune response. Perturbation of this machinery has been linked to the development of various diseases. This review describes the function of the Major Histocompatibility Complex class I antigen presentation machinery and highlights how its perturbation can lead to compromised immune function and disease progression in the context of cancer. We categorize these perturbations into four distinct mechanistic levels: peptide generation, peptide loading, MHC class I integrity, and epigenetic regulation. This enables an integrated view of their functional impact on immune recognition, supporting therapeutic efforts to target antigen presentation or exploit these alterations in cancer. Full article

(This article belongs to the Special Issue Antigen Processing in Autoimmunity and Cancer—Mechanisms and Translational Perspectives)

► Show Figures

Figure 1

26 pages, 1387 KB

Open AccessReview

SQSTM1/p62 at the Crossroads of Autophagy, Inflammation, and Lethal Infection

by Ruoxi Zhang, Rui Kang and Daolin Tang

Cells 2026, 15(7), 652; https://doi.org/10.3390/cells15070652 - 7 Apr 2026

Abstract

Sequestosome 1 (SQSTM1, also known as p62) has emerged as a multifunctional signaling adaptor that bridges autophagy, proteostasis, and inflammation. In this review, we discuss the molecular mechanisms by which SQSTM1 regulates selective autophagy and immune signaling pathways, and how its dynamic modulation [...] Read more.

Sequestosome 1 (SQSTM1, also known as p62) has emerged as a multifunctional signaling adaptor that bridges autophagy, proteostasis, and inflammation. In this review, we discuss the molecular mechanisms by which SQSTM1 regulates selective autophagy and immune signaling pathways, and how its dynamic modulation shapes host responses during sepsis. We highlight the tissue-specific roles of SQSTM1 in sepsis-associated injury across major organs—including the liver, kidney, heart, lung, brain, and skeletal muscle—and explore its function as a damage-associated molecular pattern (DAMP) in the extracellular milieu. Recent studies implicate extracellular SQSTM1 in metabolic reprogramming and pro-inflammatory cytokine production via INSR signaling, supporting its classification as a novel DAMP and potential therapeutic target. We conclude a stage- and compartment-specific model for SQSTM1 during sepsis: its transition from a protective intracellular autophagy mediator in the early stage to a pathological extracellular DAMP in late stage. Furthermore, we discuss the translational relevance of pharmacological agents that modulate SQSTM1 levels or activity to restore immune balance and organ homeostasis. A better understanding of SQSTM1’s dual roles in immune activation and resolution could open new avenues for precision therapies in sepsis. Full article

(This article belongs to the Special Issue Exclusive Reviews on Autophagy: From Molecular Mechanisms to Therapeutic Frontiers)

► Show Figures

Figure 1

44 pages, 596 KB

Open AccessReview

Sestrins as Biomarkers of Cellular Stress and Human Disease

by Alexander Haidurov and Andrei Budanov

Cells 2026, 15(7), 651; https://doi.org/10.3390/cells15070651 - 6 Apr 2026

Abstract

Sestrins are an evolutionarily conserved family of stress-responsive proteins that regulate cellular metabolism, redox balance, and survival. Their expression is induced by diverse cellular stresses through activation of transcription factors such as p53, NRF2, and FOXO. Through antioxidant activity and modulation of mTORC1 [...] Read more.

Sestrins are an evolutionarily conserved family of stress-responsive proteins that regulate cellular metabolism, redox balance, and survival. Their expression is induced by diverse cellular stresses through activation of transcription factors such as p53, NRF2, and FOXO. Through antioxidant activity and modulation of mTORC1 and mTORC2 signalling, Sestrins limit the accumulation of reactive oxygen species, regulate metabolic pathways, and promote autophagy. In this review, we analyse published studies reporting SESN1, SESN2, and SESN3 expression in human tissues, circulation, and experimental disease models. The available evidence indicates that Sestrin levels are dynamically regulated across multiple pathologies, including metabolic, ageing, cardiovascular, inflammatory, neurodegenerative, and degenerative disorders. Notably, changes in tissue Sestrin expression are often mirrored in circulation. These observations suggest that Sestrins may serve as informative biomarkers of cellular stress and disease states, and that monitoring their expression in tissues or blood could provide insight into disease progression and therapeutic response. Full article

16 pages, 2559 KB

Open AccessArticle

Modulation of L-Type Calcium Currents by Resveratrol-Induced Myogenesis in C2C12 Cells

by Andrea Biagini, Luana Sallicandro, Jasmine Covarelli, Rosaria Gentile, Alessandra Mirarchi, Alessio Farinelli, Gianmarco Reali, Diletta Del Bianco, Paola Tiziana Quellari, Elko Gliozheni, Antonio Malvasi, Giorgio Maria Baldini, Giuseppe Trojano, Claudia Tubaro, Claudia Bearzi, Roberto Rizzi, Cataldo Arcuri, Paolo Prontera, Andrea Tinelli and Bernard Fioretti

Cells 2026, 15(7), 650; https://doi.org/10.3390/cells15070650 - 6 Apr 2026

Abstract

Skeletal muscle differentiation is tightly regulated by membrane potential dynamics and voltage-dependent ion channel activity. Potassium (K⁺) and calcium (Ca²⁺) currents cooperate to orchestrate the transition of myoblasts into fusion-competent myotubes, and alterations in this process are associated with [...] Read more.

Skeletal muscle differentiation is tightly regulated by membrane potential dynamics and voltage-dependent ion channel activity. Potassium (K⁺) and calcium (Ca²⁺) currents cooperate to orchestrate the transition of myoblasts into fusion-competent myotubes, and alterations in this process are associated with dystrophic phenotypes. Here, we investigated the electrophysiological remodeling accompanying C2C12 myogenesis and the modulatory effects of the polyphenol resveratrol (RES) on calcium voltage-gated channel subunit alpha 1 S (CACNA1S, Cav1.1, L-type) currents. Whole-cell patch-clamp recordings were performed in proliferating and differentiating C2C12 cells to characterize the temporal expression of K⁺ currents and voltage-dependent Ca²⁺ channels (VDCCs). During differentiation, three electrophysiological subpopulations were identified according to K⁺ current profiles: SK4+/EAG−/Kir−, SK4−/EAG+/Kir−, and SK4−/EAG+/Kir+. This sequence paralleled a progressive membrane hyperpolarization from −20 mV to −70 mV, consistent with the physiological maturation of myogenic cells. In C2C12 myocytes, nimodipine-sensitive L-type currents were the only Ca²⁺ conductance observed. Their activation threshold (~−30 mV) and half-activation voltage (V/2 ≈ −12 mV) indicated the co-expression of embryonic and adult Cav1.1 isoforms. Exposure to RES (30 µM, 48 h) produced a depolarizing shift in activation (ΔV/2 ≈ +9 mV) and a reduction in current amplitude across all voltages, consistent with a transition toward the adult splice variant of Cav1.1. These findings suggest that RES promotes electrophysiological maturation of skeletal muscle cells by modulating calcium channel expression and gating behavior. Given its known ability to correct splicing abnormalities in CACNA1S and related genes, resveratrol emerges as a promising pharmacological agent for restoring calcium homeostasis in neuromuscular disorders such as myotonic dystrophy type 1 (DM1). Full article

► Show Figures

Figure 1

19 pages, 1526 KB

Open AccessArticle

Lipidomic and Metabolomic Profiling on Low-Count Human Spermatozoa: A Robust and Reproducible Method for Untargeted HPLC-ESI-MS/MS-Based Approach

by Irune Calzado, Manu Araolaza, Mikel Albizuri, Ainize Odriozola, Iraia Muñoa-Hoyos, Iratxe Ajuria-Morentin and Nerea Subirán

Cells 2026, 15(7), 649; https://doi.org/10.3390/cells15070649 - 5 Apr 2026

Abstract

Human infertility affects approximately 17.5% of the global population, with male factors accounting for nearly half of all cases. Identifying reliable molecular biomarkers is crucial for improving the diagnosis and assessment of male fertility. This study established and refined an untargeted high-performance liquid [...] Read more.

Human infertility affects approximately 17.5% of the global population, with male factors accounting for nearly half of all cases. Identifying reliable molecular biomarkers is crucial for improving the diagnosis and assessment of male fertility. This study established and refined an untargeted high-performance liquid chromatography–electrospray ionization–tandem mass spectrometry (HPLC-ESI-MS/MS) protocol for a comprehensive lipidomic and metabolomic analysis of human spermatozoa, using only 1.25 million cells per sample. Compared with previous reports, our optimized method achieved an unparalleled level of analytical depth, identifying 473 lipid species and 955 structurally annotated metabolites. This corresponds to nearly a 7600-fold improvement in detection efficiency per cell compared with previously published approaches. Lipidomic analysis revealed that the most abundant lipid classes were glycerophospholipids (39%), cholesterol (20%) and fatty acids (19%), with cholesterol representing the single most abundant compound. This observation is consistent with the structural complexity of the sperm plasma membrane. Metabolomic profiling similarly identified glycerophospholipids (44%), eicosanoids (14%) and N-acyl amino acids (12%) as the major metabolite classes. The integration of lipidomic and metabolomic data highlighted functionally interconnected pathways related to membrane dynamics, energy metabolism, and hormone biosynthesis. Overall, this work establishes a robust, sensitive, and scalable analytical framework that enables the high-coverage molecular characterization of spermatozoa from limited sample material, laying the groundwork for future biomarker discovery and clinical applications in male infertility research. Full article

(This article belongs to the Special Issue Sperm Biology and Reproductive Health—Second Edition)

► Show Figures

Figure 1

8 pages, 1100 KB

Open AccessCommunication

Estimation of Double-Serine Phosphorylation’s Effects on the Intrinsically Disordered Region Structure in Y14 (RBM8A) Protein via Molecular Dynamics Simulation

by Yuka Nakamura, Tetsuhiro Horie, Takuya Sakamoto, Hisayoshi Yoshizaki, Hideaki Okajima and Yasuhito Ishigaki

Cells 2026, 15(7), 648; https://doi.org/10.3390/cells15070648 - 3 Apr 2026

Abstract

The C-terminus of the Y14 protein, which is also known as RBM8A and is encoded by the gene responsible for human thrombocytopenia absent radius syndrome, contains two serines that undergo phosphorylation inside an intrinsically disordered region (IDR). Although both serines are frequently phosphorylated [...] Read more.

The C-terminus of the Y14 protein, which is also known as RBM8A and is encoded by the gene responsible for human thrombocytopenia absent radius syndrome, contains two serines that undergo phosphorylation inside an intrinsically disordered region (IDR). Although both serines are frequently phosphorylated in cells, their biological role remains unclear; therefore, we estimated the peptide structure using PEPstrMOD, which predicts peptide conformations through molecular dynamics. For this analysis, amino acid residues 151–174 of Y14, identified as an IDR in UniProt, were targeted. Structural prediction via PEPstrMOD revealed that the target peptide adopts an elongated structure in its unphosphorylated state, while simulating its phosphorylated state revealed an increase in hydrogen bonds and a more compact conformation. The compact structure of Y14 induced by phosphorylation may aid in the formation of the exon–exon junction complex at the exon–exon junction, which facilitates mRNA transport and translation. The prevalence of phosphorylated Y14 in cells may indicate that this higher-order structure is also essential for mRNA metabolism. Full article

► Show Figures

Figure 1

25 pages, 10947 KB

Open AccessArticle

Single-Cell and Spatial Transcriptomics Reveal That TXNIP and BIRC3 Contribute to Human Prostate Tumor Progression

by Seyed Taleb Hosseini, Hossein Azizi and Thomas Skutella

Cells 2026, 15(7), 647; https://doi.org/10.3390/cells15070647 - 2 Apr 2026

Abstract

Prostate cancer is one of the most prevalent malignancies among men and remains a major clinical challenge due to the complex tumor microenvironment. Understanding gene expression dynamics at both cellular and spatial levels is essential for improving therapeutic strategies. In this study, we [...] Read more.

Prostate cancer is one of the most prevalent malignancies among men and remains a major clinical challenge due to the complex tumor microenvironment. Understanding gene expression dynamics at both cellular and spatial levels is essential for improving therapeutic strategies. In this study, we performed an integrated multi-omics analysis using single-cell RNA sequencing and spatial transcriptomics. scRNA-seq data from 15 prostate samples, including 8 normal and 7 tumor tissues, were analyzed to characterize distinct cellular populations. Spatial transcriptomic profiling was conducted on three FFPE prostate tissue sections, including adjacent normal tissue, acinar cell carcinoma, and invasive adenocarcinoma, using the standard 10x Genomics Visium FFPE platform (55 µm capture spots). Single-cell analysis revealed heterogeneity among epithelial, stromal, and immune cell populations, highlighting complex signaling networks in which myeloid cells may contribute to tumor progression through immune suppression and epithelial adaptability. Spatial transcriptomic analysis further identified region-specific expression patterns and spatially restricted tumor niches, including the regional establishment of TXNIP and BIRC3 as genes associated with metabolic stress and inflammatory survival pathways. The spatial colocalization of BIRC3 with tumor vasculature in invasive carcinoma tissue suggests a novel interaction. Our discoveries using an integrated single-cell and spatial transcriptomic approach reveal a high-resolution molecular map of prostate cancer with spatial features that may provide further therapeutic investigation. Full article

(This article belongs to the Special Issue The Spatial and Temporal Dynamics of the Tumor Microenvironment)

► Show Figures

Figure 1

28 pages, 1878 KB

Open AccessReview

Adenine Nucleotide Translocase: From Nucleotide Carrier to a Modulator of Mitochondrial Bioenergetics, Quality Control, and Cellular Communication

by Ursula Rauch-Kroehnert, Jacqueline Heger, Ulf Landmesser and Andrea Dörner

Cells 2026, 15(7), 646; https://doi.org/10.3390/cells15070646 - 2 Apr 2026

Abstract

Adenine nucleotide translocase (ANT) has traditionally been defined as the ADP/ATP exchanger of the inner mitochondrial membrane. However, accumulating mechanistic evidence reveals a substantially broader functional spectrum that extends beyond nucleotide transport. In this review, we integrate these advances into a unified conceptual [...] Read more.

Adenine nucleotide translocase (ANT) has traditionally been defined as the ADP/ATP exchanger of the inner mitochondrial membrane. However, accumulating mechanistic evidence reveals a substantially broader functional spectrum that extends beyond nucleotide transport. In this review, we integrate these advances into a unified conceptual framework that positions ANT isoforms as modulators of mitochondrial bioenergetics, quality control, and cellular communication. Beyond its canonical exchange activity, ANT influences permeability transition thresholds and membrane potential stability, participates in regulated uncoupling and redox control, and contributes to inner membrane organization and cristae integrity. ANT further modulates TIMM23-dependent protein import and PINK1–Parkin-mediated mitophagy, thereby shaping mitochondrial quality control decisions. In addition, ANT regulates mitochondrial nucleic acid release and inflammasome activation, linking bioenergetic imbalance to innate immune signaling. Emerging evidence for alternative subcellular localizations suggests that ANT-dependent signaling extends mitochondrial state information to extracellular and intercellular contexts. Collectively, these findings support an expanded view of ANT as a multifunctional modulator linking mitochondrial energetic state to stress adaptation, inflammatory signaling, and tissue-level communication. Full article

(This article belongs to the Section Mitochondria)

► Show Figures

Figure 1

33 pages, 3238 KB

Open AccessReview

Cellular Processes and Forces Shaping the Embryo: Lessons from C. elegans

by Michel Labouesse, Teresa Ferraro, Flora Llense, Jonathon Heier, Zoe Tesone and Jeff Hardin

Cells 2026, 15(7), 645; https://doi.org/10.3390/cells15070645 - 2 Apr 2026

Abstract

Embryo and organ shapes emerge from the interplay between genetic programs and physical forces. In recent years, there has been a growing appreciation of the role of mechanical forces in morphogenesis. Here, we review how the integration of advanced genetic approaches with high-resolution [...] Read more.

Embryo and organ shapes emerge from the interplay between genetic programs and physical forces. In recent years, there has been a growing appreciation of the role of mechanical forces in morphogenesis. Here, we review how the integration of advanced genetic approaches with high-resolution imaging, biophysics, and modeling has begun to yield new insights into C. elegans embryonic morphogenesis. Building on past reviews in the field, we analyze dorsal intercalation, ventral enclosure, and axis extension, with a focus on how forces impinge on cellular processes and serve to coordinate morphogenesis across adjacent tissues through mechanotransduction. We also discuss how different forms of cellular rosettes contribute to ventral patterning and head morphogenesis, which had not been discussed in previous reviews. Throughout, we highlight how the reciprocal feedback mechanisms between molecular processes and mechanical forces, as well as cell material properties, shape the embryo. Full article

(This article belongs to the Section Tissues and Organs)

► Show Figures

Figure 1

42 pages, 993 KB

Open AccessReview

CRISPR–Cas9 Therapeutics in Early Clinical Development: Delivery and Molecular Diagnostics

by Adrianna Rutkowska, Tadeusz Strózik, Tomasz Wasiak, Damian Ciunowicz, Natalia Kapelan, Natalia Szczepaniak, Juliusz Sosnowski, Weronika Goślińska, Jakub Bartkowiak, Agata Budny-Lewandowska, Patrycja Antończyk, Maria Markiewicz, Piotr Gustaw, Kamil Filiks, Maria Jaskólska and Ewelina Stoczyńska-Fidelus

Cells 2026, 15(7), 644; https://doi.org/10.3390/cells15070644 - 2 Apr 2026

Abstract

CRISPR–Cas9 has progressed from an experimental tool to a therapeutic modality, marked by the first regulatory approvals of an ex vivo-edited autologous CD34+ hematopoietic stem cell product that induces fetal hemoglobin (CASGEVY/exa-cel). In this narrative review, we synthesize modality-specific molecular diagnostic strategies used [...] Read more.

CRISPR–Cas9 has progressed from an experimental tool to a therapeutic modality, marked by the first regulatory approvals of an ex vivo-edited autologous CD34+ hematopoietic stem cell product that induces fetal hemoglobin (CASGEVY/exa-cel). In this narrative review, we synthesize modality-specific molecular diagnostic strategies used across early CRISPR clinical translation. In parallel, early clinical experience has begun to demonstrate the feasibility of in vivo editing, including subretinal delivery for CEP290-associated inherited retinal degeneration (EDIT-101 programme) and hepatocyte-targeted lipid nanoparticles (LNPs) for liver-derived targets such as transthyretin and plasma prekallikrein (KLKB1). As translation expands across hematologic, metabolic, ocular and oncology indications, development is increasingly constrained by the predictability and safety of editing outcomes, delivery-determined biodistribution and exposure time, and immune recognition of bacterial Cas9 orthologs and delivery components. We summarize diagnostic readouts for confirming patient genotype, quantifying on-target editing and expression changes, assessing off-target and structural outcomes using orthogonal assays, and monitoring clonal dynamics and immune responses during long-term follow-up. We also discuss how these readouts interface with CMC controls and regulatory expectations for advanced therapy medicinal products (ATMPs), highlighting the need for fit-for-purpose, standardized testing frameworks in early trials. Full article

(This article belongs to the Special Issue The Evolving Landscape of Cell and Gene Therapy—Opportunities, Challenges and the Road Ahead)

► Show Figures

Figure 1

15 pages, 18845 KB

Open AccessArticle

FGF2 Deficiency Modulates Early Microglial Responses Without Affecting Photoreceptor Survival in a Retinitis Pigmentosa Mouse Model

by Felia C. Haffelder, Nundehui Díaz-Lezama, Zeynep Okutan, Claudia Grothe and Susanne F. Koch

Cells 2026, 15(7), 643; https://doi.org/10.3390/cells15070643 - 2 Apr 2026

Abstract

Fibroblast growth factor 2 (FGF2) is expressed in retinal Müller glia cells, and its expression increases in response to photoreceptor degeneration. To investigate the physiological relevance of FGF2, we analyzed retinal morphology and cellular responses in Fgf2-deficient (Fgf2^−/−) mice. [...] Read more.

Fibroblast growth factor 2 (FGF2) is expressed in retinal Müller glia cells, and its expression increases in response to photoreceptor degeneration. To investigate the physiological relevance of FGF2, we analyzed retinal morphology and cellular responses in Fgf2-deficient (Fgf2^−/−) mice. Loss of FGF2 did not affect photoreceptor survival, retinal vasculature, or retinal pigment epithelium (RPE) integrity. To further understand its role in retinal degeneration, Fgf2^−/− mice were crossed with Pde6b^STOP/STOP mice, a model of retinitis pigmentosa (RP). We then analyzed outer nuclear layer thickness, cone number, rod outer segments length, RPE morphology, and microglia number in Fgf2^−/− Pde6b^STOP/STOP and Pde6b^STOP/STOP mice. Although FGF2 was upregulated in degenerating photoreceptor cells in the Pde6b^STOP/STOP retina, its absence did not accelerate photoreceptor loss in Fgf2^−/− Pde6b^STOP/STOP mice. Interestingly, microglia numbers were significantly changed at early disease stages in Fgf2^−/− Pde6b^STOP/STOP retinas compared with Pde6b^STOP/STOP controls, suggesting that FGF2 modulates inflammatory signaling. Together, these results show that loss of FGF2 does not alter photoreceptor degeneration kinetics or retinal morphology, but may contribute to the regulation of early microglial accumulation during degeneration. Full article

(This article belongs to the Special Issue Translational Aspects of Cell Signaling)

► Show Figures

Figure 1

21 pages, 3900 KB

Open AccessArticle

Detecting Erythrocyte-Derived Extracellular Vesicles Generated from Blood Pump Flow and the Challenges Encountered

by Kylie M. Foster, Ahmed M. El Banayosy, Aly El Banayosy, Hendra Setiadi, Vivek K. Bajpai and Edgar A. O’Rear

Cells 2026, 15(7), 642; https://doi.org/10.3390/cells15070642 - 2 Apr 2026

Abstract

Utilization of a blood pump to aid in circulating a patient’s blood, otherwise known as mechanical circulatory support, is an effective and often life-saving treatment for cardiac/pulmonary failure patients, yet adverse events remain a common complication often attributed to mechanical trauma inflicted on [...] Read more.

Utilization of a blood pump to aid in circulating a patient’s blood, otherwise known as mechanical circulatory support, is an effective and often life-saving treatment for cardiac/pulmonary failure patients, yet adverse events remain a common complication often attributed to mechanical trauma inflicted on blood components. This work specifically focuses on erythrocyte-derived extracellular vesicles (ErEVs) as a marker of this mechanical trauma as they are elevated in patients with blood pumps and have been tied to adverse events. Despite this, ErEVs are typically neglected during device development which usually includes testing with animal blood, most commonly porcine and bovine. Flow cytometry was employed to monitor ErEVs generated during a 6 h perfusion of porcine or bovine red blood cells (RBCs) in a blood circulatory loop with the CentriMag blood pump. Successful measurement meant overcoming limitations in suitable stains for the RBCs and ErEVs of the two species. Between the two species, 12 different antibodies and dyes were evaluated, including multiple glycophorin A clones, the typical human erythrocyte antigen. Only CD46 and carboxyfluorescein succinimidyl ester (CFSE) were found to successfully and reliably label porcine and bovine RBCs, respectively. With these stains, statistically significant increases for both porcine and bovine ErEVs with perfusion time were observed. Bovine erythrocytes produced significantly more ErEVs than porcine, indicating they are more sensitive to mechanical trauma and could be useful in early-stage device development. The utility of CD46 and CFSE used for porcine and bovine ErEV detection was demonstrated for in vitro pump testing with implications for physiological and pathological research with these animals. Full article

► Show Figures

Figure 1

13 pages, 4598 KB

Open AccessArticle

Human Nasal Cells in Nanofibrillar Cellulose Hydrogel: Viability, Function, and Implications for Bone Tissue Regeneration

by Marijana Sekulic, Alina Korah, Simona Negoias, Daniel Bodmer and Vesna Petkovic

Cells 2026, 15(7), 641; https://doi.org/10.3390/cells15070641 - 2 Apr 2026

Abstract

Endoscopic sinus surgery (ESS) is commonly performed to treat chronic rhinosinusitis and selected sinonasal tumors, yet postoperative complications such as neo-osteogenesis and restenosis remain frequent, largely due to impaired mucosal regeneration after extensive epithelial and bony tissue loss. Successful nasal epithelial repair requires [...] Read more.

Endoscopic sinus surgery (ESS) is commonly performed to treat chronic rhinosinusitis and selected sinonasal tumors, yet postoperative complications such as neo-osteogenesis and restenosis remain frequent, largely due to impaired mucosal regeneration after extensive epithelial and bony tissue loss. Successful nasal epithelial repair requires a microenvironment that preserves cell viability, phenotype, and barrier integrity. Conventional culture substrates often lack physiological relevance or rely on animal-derived components, limiting translational applicability. In this study, we evaluated nanofibrillar cellulose (NFC) hydrogel (GrowDex^®) as a xeno-free scaffold for primary human nasal epithelial cells (NECs). NECs isolated from healthy donor tissue were characterized by immunofluorescence and qPCR for basal, goblet, and ciliated cell markers. Cells embedded in NFC were assessed for viability, cytotoxicity, epithelial morphology, and barrier function. Transepithelial electrical resistance (TEER) and FITC-dextran permeability assays were used to quantify barrier integrity and compared with collagen- and polylysine-based controls. NECs cultured in NFC maintained high viability, stable epithelial morphology, and preserved subtype-specific marker expression without detectable cytotoxicity. NFC-supported cultures demonstrated enhanced barrier formation, indicated by higher TEER values and reduced paracellular permeability relative to controls, and sustained structural integrity during extended culture. These findings identify NFC hydrogel as a biocompatible, non-animal scaffold that supports functional human nasal epithelium regeneration and may contribute to advanced tissue engineering strategies for craniofacial bone repair. Full article

(This article belongs to the Special Issue Advances in Tissue Engineering Approaches for Bone Repair and Regeneration)

► Show Figures

Figure 1

19 pages, 2696 KB

Open AccessReview

Peroxiredoxins in Stroke: Friends and Foes

by Yingfeng Wan, Jingwei Zhang, Liheng Bian, Xiaoxiao Tan, Ting Chen, Guohua Xi, Ya Hua, Aditya S. Pandey, Richard F. Keep and Sravanthi Koduri

Cells 2026, 15(7), 640; https://doi.org/10.3390/cells15070640 - 2 Apr 2026

Abstract

Stroke, a leading cause of mortality and long-term disability, induces complex cascades of oxidative stress and neuroinflammation that exacerbate brain injury. The peroxiredoxin (Prx; Prdx) family, composed of six thiol-dependent antioxidant enzymes (Prx1–6), plays a pivotal role in regulating redox homeostasis and immune [...] Read more.

Stroke, a leading cause of mortality and long-term disability, induces complex cascades of oxidative stress and neuroinflammation that exacerbate brain injury. The peroxiredoxin (Prx; Prdx) family, composed of six thiol-dependent antioxidant enzymes (Prx1–6), plays a pivotal role in regulating redox homeostasis and immune responses in the brain. This review synthesizes current knowledge on the isoform-specific roles of Prxs in both ischemic and hemorrhagic stroke, highlighting their dual and context-dependent functions. Intracellular Prxs generally protect neurons and maintain blood–brain barrier (BBB) integrity, while extracellular Prxs—particularly Prx1 and Prx2—act as damage-associated molecular patterns (DAMPs), activating toll-like receptor signaling and amplifying inflammation. Isoforms such as Prx3 and Prx4 exhibit mitochondrial and endothelial protective effects, respectively, whereas Prx6 demonstrates complex roles influenced by its acidic, Ca²⁺-independent, phospholipase A2 (aiPLA2) activity and cellular localization. We also discuss emerging tools for studying Prx biology and explore the translational potential of Prxs as biomarkers and therapeutic targets. Ultimately, a nuanced understanding of Prx dynamics offers new avenues for stroke diagnosis, prognosis, and treatment. Full article

► Show Figures

Figure 1

Journal Description

Cells

Latest Articles

Journal Menu

Journal Browser

Highly Accessed Articles

Latest Books

E-Mail Alert

News

Topics

Conferences

Special Issues

Topical Collections

Further Information

Guidelines

MDPI Initiatives

Follow MDPI