Cell and Tissue Research最新文献

{"title":"The systemic administration of multipotent mesenchymal stromal cells alters the inflammatory response in the lung during murine polymicrobial sepsis.","authors":"Anna Kanewska, Ina Lackner, Marco Dechant, Anne Friedrich, Martina Herrmann, Markus Rojewski, Mario Perl, Jochen Preßmar, Hubert Schrezenmeier, Miriam Kalbitz","doi":"10.1007/s00441-026-04102-4","DOIUrl":"10.1007/s00441-026-04102-4","url":null,"abstract":"<p><p>Sepsis is a life-threatening organ dysfunction and a major cause of acute respiratory distress syndrome (ARDS). Mesenchymal stromal cells (MSCs) have emerged as a potential immunomodulatory therapy, yet preclinical data remain inconsistent. This study investigated the early effects of human MSCs derived from different tissue sources-bone marrow (BMMSCs) and adipose tissue (ASCs)-on systemic and pulmonary inflammation in a murine model of polymicrobial sepsis. 60 male C57BL/6 mice underwent sham treatment, cecal ligation and puncture (CLP), or CLP followed by a single intravenous administration of BMMSCs or ASCs, manufactured according to GMP-compliant protocols. Analyses were performed 8, 24, and 72 h after CLP. Systemic inflammatory mediators were quantified by multiplex analysis, while pulmonary inflammation was assessed by mRNA and protein expression, histology, and immunofluorescence. CLP induced elevated systemic levels of pro-inflammatory mediators, which were not significantly reduced by MSC treatment. In lung tissue, however, MSC administration resulted in selective immunomodulatory effects. Expression of NLR family pyrin domain containing 3 (Nlrp3) was reduced in both MSC-treated groups, while ASC treatment additionally decreased pulmonary interleukin 6 (Il6) and complement 3a receptor (C3ar) mRNA expression at early time points. Protein levels of IL-1β, IL-6, and TNF-α were not significantly altered, although NLRP3 protein expression was reduced following ASC treatment. No significant differences in histological lung injury scores were observed between groups. In summary, MSC treatment induced modest, time-dependent attenuation of pulmonary inflammatory responses in polymicrobial sepsis without improving structural lung injury. No significant differences in pulmonary inflammatory gene expression, protein levels, or histological lung injury scores were observed between BMMSC- and ASC-treated groups, indicating that neither source demonstrated a clear immunomodulatory advantage over the other at the molecular endpoints assessed in this model.</p>","PeriodicalId":9712,"journal":{"name":"Cell and Tissue Research","volume":"406 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13722731/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149294889","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Serum and uterine fluid extracellular vesicles and prostaglandin E metabolite concentrations during diestrus and early pregnancy in mares.","authors":"Josefina Ghersa, Marilyn Mullan-Fraser, Karen Gesy, Nesma Yousif, Lynka Itogawa, Stephen Manning, Daniel J MacPhee, Claire Card","doi":"10.1007/s00441-026-04101-5","DOIUrl":"10.1007/s00441-026-04101-5","url":null,"abstract":"<p><p>Prostaglandins produced by endometrial and conceptus tissues have an established role in maintaining luteal function in early pregnancy and initiating luteolysis during diestrus in mares. The cellular mechanisms controlling the secretion and delivery of prostaglandins have not been fully elucidated. We hypothesized that nanosized lipid bilayer extracellular vesicles (EV) that carry a variety of biological molecules would be involved in these key regulatory processes. Serum and uterine fluid samples were collected from diestrus and pregnant mares on day (D) 10 and D14 post-ovulation, and conceptuses were collected in pregnant mare cycles and cultured for 2-3 h. Extracellular vesicles were isolated using membrane affinity spin columns. Metabolomic EV cargo was assessed using LC-MS/MS, and cytosolic phospholipase A2 (cPLA2) with immunoblotting. Serum and uterine fluid PGEM and conceptus PGE₂ concentrations were compared using ELISA. Prostaglandins were below detection limits in all EV serum and uterine fluid eluates. PGEM concentrations in uterine fluid and serum did not differ between pregnant and diestrus mares at these time points. Day 10 and D14 conceptuses produced PGE₂. Serum and uterine fluid EV contained AA and cPLA2. While AA abundance did not differ by reproductive status or day at these time points, uterine fluid EV AA abundance was 83 times higher than serum. Serum and uterine fluid EV carry activatable phospholipases and rate-limiting substrates for prostaglandin production rather than the prostaglandins themselves. High levels of AA in uterine fluid EV are likely important in the local regulation of uterine prostaglandin production.</p>","PeriodicalId":9712,"journal":{"name":"Cell and Tissue Research","volume":"405 3","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149236972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Functional characterization of TmToll-6 in mediating innate immune responses to systemic microbial infections in Tenebrio molitor.","authors":"Shahidul Ahmed Khan, Maryam Ali Mohmmadie Kojour, Hongray Howrelia Patnaik, Yeon Soo Han","doi":"10.1007/s00441-026-04099-w","DOIUrl":"10.1007/s00441-026-04099-w","url":null,"abstract":"<p><p>Toll-like receptors (TLRs) are evolutionarily conserved regulators of innate immunity and extensively characterized in mammals and Drosophila melanogaster; however, their functional roles in other insects remain incompletely defined. In this study, we investigated the immunological function of TmToll-6 in Tenebrio molitor larvae under systemic pathogenic bacterial and fungal challenge. Transcriptional analyses revealed that its expression was strongly induced in the fat body, gut, Malpighian tubules, and hemolymph following exposure to Escherichia coli, Staphylococcus aureus, and Candida albicans. The RNA interference-mediated silencing of TmToll-6 significantly increased larval mortality after E. coli and S. aureus infection, highlighting its essential role in antibacterial defense. Mechanistic evaluation further demonstrated that TmToll-6 knockdown markedly suppressed the antimicrobial peptide (AMP) gene expression, particularly in the fat body and gut, which are the main effector tissues of insect humoral immunity. Although TmToll-6 was strongly induced following C. albicans infection, its silencing produced comparatively limited effects on AMP expression, indicating that antifungal AMP regulation is less dependent on TmToll-6 and may involve partially redundant immune pathways. Therefore, TmToll-6 could function as a pivotal immune regulator in T. molitor through Toll pathway-dependent AMP regulation in a tissue- and pathogen-specific manner. This study highlighted the evolutionary diversification of Toll receptors in coleopteran immunity.</p>","PeriodicalId":9712,"journal":{"name":"Cell and Tissue Research","volume":"405 3","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149223377","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Constitutive UCP1 expression is associated with a glucose-dependent phenotype in murine mesenchymal stem cells.","authors":"Ulises Edgardo De-Leon-Covarrubias, Jose Juan Perez-Trujillo, Maria de Jesus Loera-Arias, Aracely Garcia-Garcia, Odila Saucedo-Cardenas, Roberto Montes-de-Oca-Luna","doi":"10.1007/s00441-026-04100-6","DOIUrl":"10.1007/s00441-026-04100-6","url":null,"abstract":"<p><p>Mesenchymal stem cells (MSCs) possess significant metabolic plasticity, enabling them to adapt dynamically to environmental stressors during tissue repair. Although UCP1 is associated with nonshivering thermogenesis in brown adipose tissue (BAT) through the uncoupling of oxidative phosphorylation, its impact on MSCs metabolism remains unexplored. Herein, we evaluated the ectopic expression of UCP1 in MSCs and its effects on classical surface markers, the redox state and glucose metabolism. MSCs were genetically modified to constitutively overexpress UCP1 using a lentiviral construct. Transduction efficiency was evaluated by direct UCP1 expression and the co-expressed EGFP fluorescent tag. Surface marker phenotype and proliferation were evaluated by expression of multipotency markers and metabolic activity, respectively. Metabolic phenotypes were assessed by measuring mitochondrial membrane potential (ΔΨm), quantifying cytoplasmic and mitochondrial reactive oxygen species (ROS), and evaluating glucose uptake via the 2-NBDG assay, while key glycolytic markers were evaluated by qPCR and immunoblot. UCP1-overexpressing MSCs showed a marked reduction in ΔΨm; however, normalized intracellular ATP levels remained stable across varying cell densities. Crucially, persistent UCP1 expression did not affect surface markers or cell metabolic activity, retaining their classical surface marker profile; furthermore, the engineered cells showed reduced baseline ROS levels compared with the parental line. Most notably, MSC-UCP1 cells showed increased glucose uptake and increased sensitivity to glucose deprivation, displaying increased expression of glycolytic markers. Our data indicate that constitutive UCP1 expression is associated with a shift in MSC metabolism towards a glucose-dependent state. This distinct metabolic profile highlights the plasticity of MSCs energetics and suggests a potential therapeutic application for genetically engineered MSCs in treating energy imbalance disorders such as obesity and type 2 diabetes.</p>","PeriodicalId":9712,"journal":{"name":"Cell and Tissue Research","volume":"405 3","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149219725","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cells for blastema formation: Lessons from the annelid regenerative model.","authors":"Toshiyuki Fujita, Shinji Yamaguchi","doi":"10.1007/s00441-026-04098-x","DOIUrl":"10.1007/s00441-026-04098-x","url":null,"abstract":"<p><p>Regeneration in many animals involves the formation of blastema, a mass of undifferentiated, proliferating cells. The origin of blastema cells is a key question in regenerative biology. Two major theories are: (1) the migration of lineage-restricted stem cells, supported by studies in salamanders and planaria, and (2) the dedifferentiation of somatic cells at the injury site, which has been observed in newts, mice, zebrafish, and crickets. Because different models support these theories, the generality of either mechanism is unclear. To address this, these theories should be investigated in a wider range of regenerative model animals. To this end, Fujita et al. (2024) studied the regenerative annelid Enchytraeus japonensis and discovered that soxC-expressing cells are crucial for blastema formation. In this review, we introduce an annelid model system for regeneration biology and the roles of soxC-expressing cells during blastema formation.</p>","PeriodicalId":9712,"journal":{"name":"Cell and Tissue Research","volume":"405 3","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13672576/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149191532","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Artificial intelligence for stromal cell quality assessment: A systematic review of human mesenchymal stromal cell properties and viability.","authors":"William Li, Himal Kandel, Stephanie Baker, J Guy Lyons, Mojdeh Abbasi, Shrushti Surya, Athanasia Vardakis, Yuri Gervasiev, Stephanie Watson","doi":"10.1007/s00441-026-04097-y","DOIUrl":"10.1007/s00441-026-04097-y","url":null,"abstract":"<p><p>Reliable assessment of mesenchymal stromal cell (MSC) viability and stem cell-associated properties is essential for ensuring the consistency, safety, and therapeutic potential of MSC cultures before clinical use. However, incomplete understanding of the mechanisms underlying MSC therapeutic effects remains a major barrier to clinical translation and to establishing reliable, standardised quality attributes. Artificial intelligence (AI) may enable automated assessment of these properties, but the performance and clinical relevance of AI-based approaches have not been systematically evaluated. This systematic review evaluated the accuracy and clinical utility of AI for assessing viability and stem cell-associated properties in human MSC cultures. Following PRISMA guidelines, we searched five electronic databases (Cochrane, Scopus, PubMed, EMBASE, and MEDLINE) for eligible studies reporting quantitative AI-based assessments of human MSC cultures. Two reviewers independently screened studies, extracted data, and assessed risk of bias using PROBAST. The review protocol was prospectively registered with PROSPERO (CRD420256393235). Of 3,872 records identified, 18 studies met the inclusion criteria. Supervised AI models, particularly convolutional neural networks, were most used. Across included studies, reported performance metrics varied substantially because of differences in AI models, imaging modalities, datasets, and outcome definitions. Considerable heterogeneity in AI model architectures, imaging modalities, outcome definitions, and reporting metrics limited direct comparison across studies. Overall, available evidence suggests that AI can assess key MSC quality attributes and may support more objective, scalable, and standardised quality-control workflows. However, broader validation, standardised reporting, external testing, and evaluation across a wider range of MSC characteristics are required before routine clinical implementation can be recommended.</p>","PeriodicalId":9712,"journal":{"name":"Cell and Tissue Research","volume":"405 3","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13672381/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149191581","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Distinct mechanism of syntaxin3-dependent tight junction assembly in keratinocyte model cells.","authors":"Akari Kitadai, Yume Inoue, Junya Abe, Yohei Hirai","doi":"10.1007/s00441-026-04096-z","DOIUrl":"10.1007/s00441-026-04096-z","url":null,"abstract":"<p><p>In the epidermis, differentiated keratinocytes form tight junctions (TJs) at a specific layer of the stratified epithelium, contributing to the skin barrier function. Previously, we demonstrated that the t-SNARE protein Syntaxin3 (Stx3) is necessary for TJ assembly in differentiated HaCaT keratinocytes. In simple epithelial cells, the apical targeting signal (ATS), located within helix a of Stx3, appears to be essential for TJ formation. Here, using Stx3-knockout HaCaT cells with inducible expression of various Stx3 mutants, we present a distinct mechanism of Stx3-dependent TJ assembly in epidermal keratinocytes that have lost apicobasal polarity. We found that in differentiated HaCaT cells, Stx3 lacking ATS still retains the ability to induce TJ formation, but replacing helices a and b with those of its paralogue epimorphin/Stx2 eliminated this ability. Intriguingly, a subpopulation of wild-type Stx3 appeared to be exposed to the extracellular space upon differentiation, and extracellular addition of a recombinant form of Stx3 supported TJ assembly. We also found that substituting only the six amino acids in helix b of Stx3 (SMEKHI) with the corresponding motif from Stx2, known as the functional core of extracellular Stx2, completely abolished this ability. These findings suggest that the differentiation-induced extrusion of Stx3 is crucial for TJ assembly in differentiated keratinocytes, with the possible core motif in helix b playing an essential role, providing new insights into the spatiotemporal dynamics of TJ formation in the stratified epidermis.</p>","PeriodicalId":9712,"journal":{"name":"Cell and Tissue Research","volume":"405 2","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149029957","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Decoding stem cell preconditioning as a novel strategy for improving its therapeutic efficacy in intervertebral disc regeneration.","authors":"Yee Ying Tan, Chee Kidd Chiu, Ali Mohammad Sharifi, Krishnamurithy Genasan","doi":"10.1007/s00441-026-04094-1","DOIUrl":"10.1007/s00441-026-04094-1","url":null,"abstract":"<p><p>Intervertebral disc degeneration (IDD) is one of the major contributors to chronic low back pain, imposing a significant global socioeconomic burden. IDD is primarily driven by the degeneration of nucleus pulposus cells (NPCs) within the intervertebral disc (IVD), mainly due to oxidative stress, which leads to excessive reactive oxygen species (ROS) accumulation. ROS activate inflammatory and catabolic signaling pathways, resulting in degradation of the extracellular matrix (ECM) and progressive disc failure. Current treatments scarcely address the underlying biological mechanisms and fail to restore disc integrity. Mesenchymal stem cell (MSC)-based intervention has emerged as promising solution for disc regeneration due to its potential to mitigate inflammation and promote matrix synthesis. However, the avascular and proinflammatory environment of the degenerated disc limits cell-based interventions, as transplanted cells exhibit poor survival and engraftment after transplantation. To overcome these limitations, preconditioning strategies have been developed both to enhance direct MSC survival/engraftment and to optimize cell-free therapies utilizing preconditioned MSC secretome/extracellular vesicles. Preconditioning MSCs using various stimuli can improve their therapeutic performance by releasing factors that can support cell viability, reduce apoptosis, and increase cells' resilience to oxidative stress. Despite these promising findings, there remains a lack of comprehensive understanding regarding their role in IDD treatment. This review examines current MSC-based therapies, the mechanisms behind various preconditioning strategies, and the translational challenges that remain unexplained. Ultimately, preconditioned MSC-derived products offer a novel and potentially more effective approach for intervertebral disc regeneration.</p>","PeriodicalId":9712,"journal":{"name":"Cell and Tissue Research","volume":"405 2","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149015658","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From channels to communication networks: a perspective on connexins, pannexins and innexins.","authors":"Trond Aasen, James W Smyth, Silvia Penuela","doi":"10.1007/s00441-026-04095-0","DOIUrl":"10.1007/s00441-026-04095-0","url":null,"abstract":"","PeriodicalId":9712,"journal":{"name":"Cell and Tissue Research","volume":"405 2","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148982019","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A proposed mechanism of ammonia excretion in the seahorse brood pouch revealed by rhesus glycoprotein localization.","authors":"Hiroki Yamazaki, Junya Hiroi, Shigeki Yasumasu, Mari Kawaguchi","doi":"10.1007/s00441-026-04093-2","DOIUrl":"10.1007/s00441-026-04093-2","url":null,"abstract":"<p><p>In seahorses (family Syngnathidae), the male brood pouch provides a protected environment for developing embryos. During pregnancy, embryos develop within an enclosed brood pouch, requiring a physiological mechanism to eliminate the nitrogenous waste excreted by the embryos. This study investigated the expression and localization of rhesus (Rh) glycoproteins, expected to function as ammonia transporters, in the brood pouch of the pot-bellied seahorse Hippocampus abdominalis. The expression of the RhAG, RhBG, and RhCG2 genes in the pouch was confirmed by reverse transcription-polymerase chain reaction (RT-PCR). In situ hybridization and immunohistochemistry revealed that RhBG and RhCG2 are localized in the inner epithelium of the pouch, while RhAG is present in erythrocytes and the endothelium of the blood vessels. Based on these findings, we propose the following waste removal pathway. Ammonia, presumably released from the embryo, would be transported from the lumen of the pouch through apical RhCG2 and basolateral RhBG of inner epithelial cells into the connective tissue beneath the inner epithelium. In the connective tissue, ammonia passes through RhAG-expressing endothelial cells into the vascular lumen and is likely taken up by RhAG-expressing erythrocytes, which then travel to the gills via the bloodstream. Then, ammonia is released from the RhAG-expressing erythrocytes through RhAG-expressing pillar cells, basolateral RhBG- and apical RhCG2-expressingpavement cells, finally into the surrounding seawater. This study provides a first molecular and cellular basis for a proposed ammonia removal mechanism within the seahorse brood pouch, highlighting physiological adaptations associated with male pregnancy in syngnathid fish.</p>","PeriodicalId":9712,"journal":{"name":"Cell and Tissue Research","volume":"405 2","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148900292","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}