Tissue & cell最新文献

{"title":"Lipid metabolism-associated immune gene LPL promotes M1 macrophage polarization and inhibits breast cancer progression.","authors":"Lu Yang, Xuan Fang, Xu Liu, Yu Liu, Shaorong Zhao","doi":"10.1016/j.tice.2025.103071","DOIUrl":"10.1016/j.tice.2025.103071","url":null,"abstract":"<p><strong>Background: </strong>Breast cancer (BRCA) ranks among the most frequently diagnosed malignancies worldwide. Immune infiltration plays a critical role in tumor progression and therapeutic response. However, the precise mechanisms underlying immune infiltration in BRCA remain incompletely understood.</p><p><strong>Methods: </strong>Machine learning (support vector machine-recursive feature elimination and least absolute shrinkage and selection operator regression) and weighted gene co-expression network were utilized to screen hub genes. An immune infiltration assessment was carried out via TIMER and CIBERSORT. The prognostic and survival of risk model and immune infiltration-associated hub genes were analyzed through Kaplan-Meier survival analysis, Cox regression, and ROC curve evaluation. Cell functional assays and xenograft models in vivo were utilized to examine lipoprotein lipase (LPL) function. The impact of LPL on macrophage polarization was evaluated using THP-1-derived macrophages and immunohistochemistry analysis of immune infiltration (CD4, CD8, and F4/80) in vivo.</p><p><strong>Results: </strong>10 hub immune regulators were identified in BRCA, which were associated with lipid metabolism. Hub genes and a prognostic risk model exhibited high predictive accuracy for BRCA patient survival and prognosis. Overexpression of LPL inhibited BRCA cell proliferation, migration, and invasion while promoting M1-like macrophage polarization. In vivo, LPL overexpression significantly suppressed tumor growth and enhanced immune cell infiltration, as indicated by the elevation of CD4 + and F4/80 + cells along with a decline in CD8 + macrophage abundance.</p><p><strong>Conclusion: </strong>This study identifies a novel lipid metabolism-related gene signature and demonstrates that LPL overexpression modulates macrophage polarization and inhibits BRCA progression.</p>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"97 ","pages":"103071"},"PeriodicalIF":2.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144804922","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aluminum oxide nanoparticles induce neurodegeneration via oxidative stress, amyloidogenic pathway activation, and BDNF suppression in rat brain.","authors":"Yasser S El-Sayed, Dalia H Samak, Hamida M Saleh, Marium B Aboshoom, Amira E Shehata, Shahenaz M Hassan","doi":"10.1016/j.tice.2025.103070","DOIUrl":"10.1016/j.tice.2025.103070","url":null,"abstract":"<p><p>Aluminum oxide nanoparticles (Al₂O₃NPs) are used across industrial and consumer sectors, raising concerns about their potential neurotoxic effects. Despite growing application, the mechanisms underlying Al₂O₃NP-induced neurodegeneration remain poorly understood. This study investigated the mechanistic pathways of Al₂O₃NP neurotoxicity in adult male Sprague-Dawley rats exposed intraperitoneally to 15, 30, or 60 mg/kg Al₂O₃NPs for 60 days. Comprehensive analyses included hematological profiling, serum biochemistry, oxidative stress markers (MDA, Nrf2/Keap1), neurotransmitter assays (dopamine, acetylcholine, AChE), quantitative PCR of APP, BACE1, and BDNF, inductively coupled plasma spectroscopy for brain aluminum levels, histopathology, immunohistochemistry (caspase-3, BCL2), and ultrastructural examination by transmission electron microscopy. Al₂O₃NP exposure induced dose-dependent anemia, disrupted iron and calcium homeostasis, and triggered oxidative stress, evidenced by elevated MDA and suppressed Nrf2/Keap1 signaling. Neurochemical analyses revealed marked dopamine and acetylcholine depletion alongside diminished AChE activity. Molecular assays showed significant upregulation of amyloidogenic markers (APP, BACE1) and severe BDNF suppression, indicating impaired neurotrophic support. Brain histopathology revealed progressive neuronal shrinkage, Purkinje cell loss, astrogliosis, and perivascular edema, while immunohistochemistry demonstrated heightened caspase-3 activation and reduced BCL2 expression. TEM confirmed ultrastructural axonal degeneration, demyelination, and necrotic neuronal profiles. Notably, aluminum bioaccumulation increased 116-fold at the highest dose, tightly correlating with neurodegeneration severity. These findings demonstrate that subchronic Al₂O₃NP exposure promotes neurodegeneration via a multifaceted oxidative stress mechanism, activating the amyloidogenic pathway, synaptic dysfunction, neurotrophic impairment, and apoptosis. This work underscores the urgent need for rigorous safety assessments of nanoparticle exposure in biomedical and environmental settings.</p>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"97 ","pages":"103070"},"PeriodicalIF":2.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144800289","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of the potential protective effect of hydrogen-rich saline against brain injury in experimental head trauma model in rats.","authors":"Murat Kayabaş, Mustafa Makav, Serdar Yi̇ği̇t, Levent Aras, Levent Şahi̇n, Menekşe Bulut, Duried Alwazeer","doi":"10.1016/j.tice.2025.103076","DOIUrl":"10.1016/j.tice.2025.103076","url":null,"abstract":"<p><p>‎Head trauma is one of the main reasons for morbidity and mortality in motor vehicle and work accidents. This study aimed to evaluate the effect of hydrogen on head trauma injury. The study groups were divided into four groups, with six rats in each group as follows: Control or no treatment (group C), Head Trauma Injury (group HI), Hydrogen-rich Saline (group H2), and Head Trauma Injury + hydrogen-rich saline (group HI+H2). Blood and brain tissues, serum, interleukin (IL-6), and tumor necrosis factor (TNF-α) parameters were analyzed. Histopathologically, hematoxylin-eosin and TUNEL staining were performed on the tissue samples. A significant increase in TNF-α and IL-6 levels in the HI group that decreased when hydrogen-rich saline was applied, i.e., the HI+H2 group. Histopathologically, a decrease in degenerative cells was observed in the treatment group (i.e., HI+H2). TUNEL staining also showed a decrease in the number of stained cells in the HI+H2 group compared to the HI group. It is thought that hydrogen-rich saline treatment may be suggested to alleviate the damage caused by head trauma injury.</p>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"97 ","pages":"103076"},"PeriodicalIF":2.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144800290","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"USP7 represses ferroptosis in trophoblasts in pre-eclampsia by mediating the xCT/GPX4 axis via deubiquitination of NRF2.","authors":"Shaohua Wu, Zhongqin Wang, Lin Wang","doi":"10.1016/j.tice.2025.103050","DOIUrl":"10.1016/j.tice.2025.103050","url":null,"abstract":"<p><strong>Objective: </strong>Trophoblasts, a unique placental cell type, are sensitive to ferroptosis. Targeting trophoblast ferroptosis may be protective against trophoblast damage in patients with pre-eclampsia (PE). Herein, this study probed the role of the deubiquitinating enzyme ubiquitin-specific protease 7 (USP7) in trophoblast ferroptosis during PE.</p><p><strong>Methods: </strong>Trophoblasts (HTR-8/SVneo) were subjected to hypoxia treatment to simulate the placental status in PE. USP7 expression in hypoxia-treated HTR-8/SVneo cells was measured. After gain- and loss-of-function assays in hypoxia-treated HTR-8/SVneo cells, biological activities, such as viability, invasion, migration, and ferroptosis, were detected. NRF2, x-CT, and GPX4 expression levels were examined. The binding between NRF2 and USP7 was analyzed.</p><p><strong>Results: </strong>USP7 expression was reduced in hypoxia-treated HTR-8/SVneo cells. Cell viability, invasion, and migration were notably decreased, but ferroptosis was markedly enhanced in hypoxia-treated HTR-8/SVneo cells. Erastin treatment stimulated ferroptosis, which was blocked by USP7 overexpression or ferroptosis inhibitor. Mechanistically, NRF2 bound to USP7, and USP7 induced NRF2 deubiquitination and repressed its degradation. Overexpression of USP7 upregulated x-CT and GPX4 in hypoxia-treated HTR-8/SVneo cells. NRF2 knockdown counteracted changes in biological properties and ferroptosis of hypoxia-treated HTR-8/SVneo cells caused by USP7 overexpression.</p><p><strong>Conclusion: </strong>USP7-mediated NRF2 deubiquitination stabilizes NRF2 and activates the xCT/GPX4 pathway, suppressing trophoblast ferroptosis in the setting of PE. This study highlights a promising strategy against trophoblast ferroptosis and supports the development of new therapies for PE.</p>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"97 ","pages":"103050"},"PeriodicalIF":2.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144800291","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lupeol induces apoptosis of glioma cells via governing ubiquitination-mediated SPARC turnover.","authors":"Yiting Wei, Yulin Wan, Shilong Duan, Qiongyao Hu, Nanjian Xu","doi":"10.1016/j.tice.2025.103039","DOIUrl":"10.1016/j.tice.2025.103039","url":null,"abstract":"<p><p>Glioblastoma multiforme (GBM) remains a lethal malignancy with limited therapeutic options due to its aggressive progression and resistance to apoptosis. SPARC (secreted protein acidic and rich in cysteine), a multifunctional glycoprotein implicated in glioma survival and chemoresistance, is stabilized by deubiquitinating enzymes (DUBs), yet the regulatory mechanisms driving its turnover are poorly defined. Lupeol, a natural triterpenoid, exhibits anticancer potential, but its effects on glioma and underlying molecular mechanisms remain elusive. Here, we demonstrate that lupeol induces apoptosis in glioma cells by targeting ubiquitination-mediated SPARC degradation. Mechanistically, lupeol enhanced SPARC polyubiquitination by disrupting its interaction with ubiquitin-specific protease 14 (USP14), a DUB that antagonizes proteasomal degradation of SPARC. These findings unveil a novel mechanism by which lupeol triggers apoptosis through USP14-dependent SPARC ubiquitination and degradation, highlighting the therapeutic potential of targeting the USP14-SPARC axis in glioma treatment. This study provides the first evidence linking lupeol's anticancer activity to ubiquitination-regulated protein turnover, offering insights for developing SPARC-directed therapies against gliomas.</p>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"97 ","pages":"103039"},"PeriodicalIF":2.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144804869","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unlocking the potential of EXOs in regenerative medicine: A comprehensive review.","authors":"Tayebeh Sadat Tabatabai, Morteza Alizadeh, Leila Rezakhani, Tahereh Sadat Tabatabai, Arian Ehterami, Shahin Gharedaghi Kloucheh, Maziar Malekzadeh Kebria, Ahmad Vaez, Majid Salehi","doi":"10.1016/j.tice.2025.103068","DOIUrl":"10.1016/j.tice.2025.103068","url":null,"abstract":"<p><p>Extracellular vesicles (EVs), particularly exosomes (EXOs), are essential in cellular communication and play significant roles in various physiological and pathological processes. Ranging in size from 30 to 150 nm, EXOs are lipid vesicles derived from the endosomal system and characterized by their distinctive cup-shaped morphology. These vesicles are produced by hematopoietic and non-hematopoietic cells and are found in all body fluids, including blood plasma, cerebrospinal fluid, urine, saliva, and breast milk. EXOs are equipped to transfer a myriad of bioactive materials-proteins, lipids, nucleic acids, and microRNAs-to recipient cells locally and distantly, potentially altering cellular function and influencing the microenvironment. Given their significant roles, this review comprehensively examines the various aspects of EXOs, from their biogenesis and preparation to their isolation and detailed characterization. We discuss the necessity of understanding these fundamental aspects to harness EXOs' potential in clinical applications, particularly in regenerative medicine. The review highlights the latest advances in using EXOs as carriers for therapeutic molecules, ranging from small molecules and genes to large therapeutic proteins and nanoparticles, emphasizing their application in drug delivery for cancer treatment and immunotherapy. Moreover, the paper delves into the promising applications of EXOs in tissue repair and regeneration, detailing specific cases in skin, bone, cartilage, heart, lung, and neurological diseases, among others. Each section explores not only the therapeutic potential but also the underlying mechanisms by which EXOs facilitate these regenerative processes. By discussing the clinical applications and inherent challenges of utilizing EXOs, this review underscores the critical need for continued research to fully exploit EXOs' therapeutic capabilities, offering insights into their future implications in medicine.</p>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"97 ","pages":"103068"},"PeriodicalIF":2.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144812439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Endometrial regeneration and the role of the extracellular matrix: mechanisms, challenges, and future perspectives.","authors":"Zahra Asadikalameh, Mahsa Esgandari, Paria Panahinia, Shiva Ghayur, Ramina Fazeli, Atoosa Etezadi","doi":"10.1016/j.tice.2025.103074","DOIUrl":"10.1016/j.tice.2025.103074","url":null,"abstract":"<p><p>Endometrial regeneration is a cornerstone of reproductive health, with the extracellular matrix (ECM) playing a pivotal role in tissue repair, regeneration, and fertility restoration. Dysregulated ECM remodeling is at the heart of many debilitating conditions, including infertility, endometriosis, Asherman's syndrome, and uterine fibroids, all of which disrupt the delicate balance necessary for effective endometrial regeneration. This review presents a cutting-edge analysis of ECM dynamics, emphasizing its central role in the endometrial regeneration process and highlighting novel ECM-targeted therapies that hold transformative potential for addressing these complex disorders. We focus on emerging strategies such as stem cell-based therapies, growth factor modulation, matrix metalloproteinase inhibition, and peptide-based interventions that precisely regulate ECM composition to promote healing and restore functionality to the endometrium. Revolutionary technological advancements, including 3D bioprinting, biocompatible ECM scaffolds, and organoid models, are providing new avenues for personalized therapeutic approaches aimed at optimizing ECM interaction and enhancing regenerative outcomes for individual patients. Despite these promising developments, significant challenges remain in evaluating the long-term safety and efficacy of ECM-targeted treatments. This review also identifies critical knowledge gaps, particularly in understanding the molecular mechanisms governing ECM remodeling in the endometrial context, urging further exploration to unlock the full therapeutic potential of ECM-based regeneration strategies. Through precise modulation of ECM dynamics, this research sets the stage for innovative treatments that could revolutionize the management of uterine dysfunction and significantly enhance fertility restoration.</p>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"97 ","pages":"103074"},"PeriodicalIF":2.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144804921","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of HIF signal mediated autophagy dysfunction in synovial fibroblasts in rheumatoid arthritis and the targeted regulation of kaempferol.","authors":"Meng Li, Chao Song, Ming Dai","doi":"10.1016/j.tice.2025.103172","DOIUrl":"https://doi.org/10.1016/j.tice.2025.103172","url":null,"abstract":"<p><strong>Background: </strong>Rheumatoid arthritis (RA) is an autoimmune condition that causes joint damage and persistent synovial inflammation. Recent research has demonstrated the critical roles that fibroblastic synoviocytes (FLS) autophagy abnormalities, hypoxia inducible factor (HIF) signaling activation, and aberrant production of inflammatory factors play in the pathophysiology of RA. Although kaempferol is a naturally occurring flavonoid with anti-inflammatory, antioxidant, and other biological properties, it is yet unknown how it controls FLS autophagy in RA.</p><p><strong>Methods: </strong>To screen for autophagy-associated core genes, this study used transcriptome data related to RA in conjunction with weighted gene co-expression network analysis (WGCNA) and LASSO regression. The function of immune cells in RA lesions was investigated in conjunction with immune infiltration research, and in vitro cell tests confirmed kaempferol's regulatory effect on important genes.</p><p><strong>Results: </strong>Through screening, 8 key genes that are intimately linked to RA autophagy were found. In addition to IL-17 signaling and aberrant mitochondrial autophagy, it was discovered that the HIF signaling pathway was highly activated in RA synovial cells, which promoted inflammatory responses and aberrant cell proliferation. Significant neutrophil and macrophage aggregation was revealed by immune infiltration studies, aggravating inflammation and hypoxia in synovial tissue. Kaempferol controlled the expression of key genes such HIF1A, MYC, and HMOX1, enhanced mitochondrial activity, and dramatically reduced the proliferation of FLS, according to cell tests.</p><p><strong>Conclusion: </strong>This study reveals the molecular mechanism of autophagy imbalance in FLS in RA, emphasizes the synergistic effect of HIF-IL17 mitochondrial autophagy pathway, and clarifies the potential of kaempferol to exert therapeutic effects by regulating this pathway, providing new ideas for targeted therapy of RA.</p>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"98 ","pages":"103172"},"PeriodicalIF":2.5,"publicationDate":"2025-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145245446","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The effect of glyphosate-based herbicide on the postnatal development of the rat cerebellar cortex in male albino rats: Biochemical, anatomical, histopathological, and immunohistochemical assessments.","authors":"Amira Hamed Mohamed Soliman, Hanan M Alharbi, Mujtaba Farooq Rana, Heba H Mahboub, Mohamed Wagdy, Rasha M M Ezz-Eldin","doi":"10.1016/j.tice.2025.103167","DOIUrl":"https://doi.org/10.1016/j.tice.2025.103167","url":null,"abstract":"<p><p>This work was designed to assess the Gly-BH impacts on the postnatal development of rat cerebellum via evaluation of locomotor activity, histological and immunohistochemical studies, and to focus on cerebellar oxidative stress-related alterations. Twenty-four new-born pups were divided into 2 equal experimental groups: the control group was kept without any treatment and Gly-BH treated group in which their mothers received (100 mg/kg b.w./day) in drinking water from 1st day of gestation to the end of pregnancy. six rats of each group were weighed deeply anesthetized and sacrificed at postnatal day-11 (PD11) and PD30 ages. For locomotor assessment, rats were tested at the PD28-30 ages. Gly-BH-treated rats suffered from decreased motor activity and showed decreased body and cerebellar weights, reduced levels of enzymatic antioxidants (SOD and CAT), and non-enzymatic antioxidant defence (GSH), and increased lipid peroxidation marker (MDA). Histopathological assessment exhibited that Gly-BH resulted in deleterious changes within cerebellar cortical layers in the form of vacuolations, decreased thickness, while Purkinje cells exhibited profound degenerative changes. In Gly-BH-treated rats, GFAP demonstrated upregulated, hypertrophied, and branched Bregman glial fibers and reactive astrogliosis. Immunolocalization of Ki-67 positive cells revealed decreased proliferation in PD11. Nevertheless, the Gly-BH-treated rats showed decreased synaptophysin immunolocalization in all cerebellar layers and on the surface of Purkinje cells. In conclusion, Gly-BH causes oxidative stress-related deleterious effects on the structure of developing cerebellar cortex and affects locomotor activity.</p>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"98 ","pages":"103167"},"PeriodicalIF":2.5,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145245432","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Graphene oxide nanoscaffold functionalized with adipose-derived mesenchymal stem cells and sildenafil promotes urethral stricture repair and tissue regeneration","authors":"Marcela Durán ,&nbsp;Gabriela Cardoso de Arruda Camargo ,&nbsp;Gabriela Oliveira ,&nbsp;João Carlos Cardoso Alonso ,&nbsp;Paulo César Martins Alves ,&nbsp;Bruno Bosh Volpe ,&nbsp;José Ronaldo de Castro Roston ,&nbsp;Sergio San Juan Dertkigil ,&nbsp;Angela Cristina Malheiros Luzo ,&nbsp;Nelson Durán ,&nbsp;Wagner José Fávaro","doi":"10.1016/j.tice.2025.103171","DOIUrl":"10.1016/j.tice.2025.103171","url":null,"abstract":"<div><div>Urethral stricture is a common and challenging urological disorder marked by fibrotic narrowing of the urethral lumen, which leads to urinary obstruction and diminished quality of life. Current surgical options are associated with high recurrence rates and limited tissue regeneration. To address these limitations, we developed a multifunctional therapeutic platform integrating a nanostructured graphene oxide scaffold functionalized with polyethylene glycol and poly(ε-caprolactone) (GO/PEG-NH₂/PCL), seeded with human adipose-derived mesenchymal stem cells (ADMSCs) and combined with oral sildenafil. In vitro analyses confirmed scaffold biocompatibility and sustained ADMSC viability, as assessed by fluorescence microscopy, with preservation of spindle-shaped morphology at low GO concentrations. In vivo, we employed a rabbit model of surgically induced urethral stricture and compared four groups: Control, Stricture, Scaffold+ADMSCs, and Scaffold+ADMSCs+Sildenafil. Ten weeks post-treatment, histological and immunohistochemical evaluations revealed that the combinatorial approach significantly restored urethral architecture and lumen patency. This was accompanied by reduced collagen deposition, enhanced smooth muscle organization, and upregulated expression of epithelial differentiation markers (Uroplakin, Desmocollin) and progenitor markers (CD117), alongside downregulation of the fibrotic mediator MMP2. Quantitative scoring indicated that fibrosis and inflammation levels in the treated group approached those of normal tissue. The GO/PEG-NH₂/PCL nanoscaffold supported ADMSC adhesion and differentiation, while sildenafil provided complementary antifibrotic and angiogenic modulation. Together, these findings support this composite system as a promising regenerative strategy for functional urethral repair, offering translational relevance for the management of complex urethral strictures.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"98 ","pages":"Article 103171"},"PeriodicalIF":2.5,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145225992","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}