Tissue engineering and regenerative medicine最新文献

{"title":"Effects of Cryopreservation on Stromal Vascular Fraction Viability in Human Adipose Tissue: Insights from a Systematic Review.","authors":"Sadia Farhana, Mohd Zulkifli Salleh, Shazana H Shamsuddin, Nur Azida Mohd Nasir","doi":"10.1007/s13770-026-00833-1","DOIUrl":"https://doi.org/10.1007/s13770-026-00833-1","url":null,"abstract":"<p><strong>Background: </strong>Cryopreservation of human adipose tissue facilitates long-term storage and repeated clinical application in tissue engineering and regenerative medicine. However, its quantitative impact on stromal vascular fraction (SVF) viability remains inconsistently characterized across studies with heterogeneous reporting formats. This study systematically evaluated the effect of cryopreservation on SVF viability and key procedural and donor-related determinants influencing post-thaw preservation quality.</p><p><strong>Methods: </strong>A systematic search of PubMed, Scopus, Web of Science, Cochrane Library, and ScienceDirect (January 2008-January 2025) identified in vitro and in vivo studies assessing cryopreserved human adipose tissue. Methodological quality was evaluated using the Joanna Briggs Institute (JBI) critical appraisal tools. Quantitative synthesis included a meta-analytic pooling of available comparable datasets alongside exploratory correlation analyses to examine associations between cryopreservation parameters and SVF viability.</p><p><strong>Results: </strong>Seventeen studies met inclusion criteria, with six eligibles for quantitative meta-analysis. Pooled SVF viability was 0.062 × 10⁵ cells/g (95% CI 0.50-0.74 × 10⁵) in cryopreserved samples and 0.054 × 10⁵ cells/g (95% CI 0.42-0.65 × 10⁵) in fresh tissue, with substantial heterogeneity (I² > 98%). Viability negatively correlated with freezing duration (r =  - 0.644) and prolonged enzymatic digestion (r =  - 0.417), whereas freezing temperature showed minimal effect (r =  - 0.093). Short-term storage (< 1 month), lower temperatures (- 80 °C or - 196 °C), and cryoprotectants such as DMSO and trehalose improved preservation outcomes.</p><p><strong>Conclusion: </strong>Cryopreservation preserves SVF viability at levels broadly comparable to fresh tissue, likely due to methodological variability across studies rather than true biological superiority in regenerative capacity. Post-thaw SVF quality is influenced more by cumulative processing and storage conditions than by freezing temperature alone. However, standardization of protocols and incorporation of functional potency assays beyond viability metrics are still essential to optimize clinical adipose tissue biobanking.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148798229","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Pilot Study for Establishing DSS-Induced Colitis Model in Minipigs.","authors":"Hye Won Park, Woon Kyu Lee","doi":"10.1007/s13770-026-00832-2","DOIUrl":"https://doi.org/10.1007/s13770-026-00832-2","url":null,"abstract":"<p><strong>Background: </strong>Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by relapsing and remitting colonic mucosal inflammation. Rodent dextran sodium sulfate (DSS) induced colitis models are widely used but have limited translational relevance due to anatomical and physiological differences. As a pilot feasibility study, this work aimed to explore whether graded DSS administration could induce reproducible colitis-like features in minipigs.</p><p><strong>Methods: </strong>We developed a pilot large-animal UC model using Sus scrofa minipigs. Eight male Micropigs® were divided into four groups, with three groups receiving DSS at 0.2, 0.4, or 0.8 g/kg/day for 7 days. Clinical signs, body weight, colon length, endoscopic evaluation, and histopathology were assessed.</p><p><strong>Results: </strong>DSS administration induced dose-dependent UC features. Group 4 minipigs (0.8 g/kg/day) showed the most severe clinical manifestations, including diarrhea, anorexia, and lethargy. Colon length was reduced by 34% in Group 4 compared to controls. Endoscopy revealed progressive mucosal edema, hemorrhage, and erosions. Histopathological scoring confirmed severe inflammation, crypt loss, and ulceration in higher-dose groups. Dose-dependent trends were consistently observed across clinical signs, endoscopic findings, and histopathological features.</p><p><strong>Conclusion: </strong>This DSS-induced minipig colitis model replicates clinical, endoscopic, and histological hallmarks of human UC. As an exploratory pilot study, it provides proof-of-concept for minipigs as a translational platform for inflammatory bowel disease (IBD) research and therapeutic evaluation.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148702258","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Harnessing Artificial Intelligence for Regeneration of Endometrium in Asherman's Syndrome.","authors":"Gokulnath Anbalagan, Namasivaya Naveen Shanmuga Sundaram, Nandakumar Venkatesan","doi":"10.1007/s13770-026-00810-8","DOIUrl":"10.1007/s13770-026-00810-8","url":null,"abstract":"<p><strong>Background: </strong>Asherman's Syndrome or intrauterine adhesions develop due to acquired endometrium damage, resulting in partial to complete dysfunction of the endometrium within the uterine cavity. The pathophysiology of these adhesions is not clear. Still, the widely accepted mechanism for the development of these adhesions is attributed to three different causes: i. iatrogenic or mechanical, including curettage; ii. pathophysiological conditions, including infection, miscarriage, and Müllerian malformations; and iii. idiopathic.</p><p><strong>Objective: </strong>This review critically evaluates the different therapeutic strategies used to manage or treat Asherman's syndrome and the various issues associated with each treatment.</p><p><strong>Methods: </strong>A thorough literature review was performed for other types of polymers currently used or tested for the regeneration of endometrium both clinically and preclinically, and the issues associated with each of the polymers are also discussed.</p><p><strong>Results: </strong>Finally, we conclude the manuscript by exploring Artificial Intelligence's role in predicting, classifying, and identifying intrauterine adhesions, including machine learning and deep learning algorithms. We also discuss the role of AI in improving biomaterial properties, enhancing stem cell viability, and refining AI-driven diagnostic and therapeutic strategies for better clinical outcomes.</p><p><strong>Conclusion: </strong>In alignment with the United Nations Sustainable Development Goal 4 (Quality Education), this review aims to promote advanced interdisciplinary learning by integrating biomedical engineering, materials science, and artificial intelligence to educate and empower future researchers in regenerative medicine.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":" ","pages":"791-813"},"PeriodicalIF":5.1,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13415714/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148158245","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Thermosensitive Injectable Hydrogel Incorporating Telopeptide-Free Type I Collagen Promotes Cartilage Regeneration: An In Vivo Study.","authors":"Lilan Gao, Henglin Zhang, Xianglong Lin, Yanliuxing Yan, Yansong Tan, Chunqiu Zhang","doi":"10.1007/s13770-026-00813-5","DOIUrl":"10.1007/s13770-026-00813-5","url":null,"abstract":"<p><strong>Background: </strong>In cartilage tissue engineering, successfully mimicking the natural extracellular matrix is essential for promoting hyaline cartilage regeneration. The triple-helix structure of collagen has been identified as a critical element in this process, though preserving this structure while minimizing immunogenicity remains a significant challenge.</p><p><strong>Methods: </strong>This study employed high-precision enzymatic digestion technology to specifically remove immunogenic terminal fragments from collagen while preserving its functional triple-helix configuration. The resulting collagen-based hydrogel was engineered with thermosensitive properties, enabling it to adaptively fill irregular cartilage defects and undergo rapid gelation at body temperature.</p><p><strong>Result: </strong>The modified collagen hydrogel demonstrated significantly improved biological safety, with complement activation levels substantially decreasing following removal of terminal peptide segments-confirming the immunogenic role of these regions. Mechanically, the hydrogel successfully replicated the viscoelastic characteristics of natural cartilage, exhibiting matched dynamic mechanical properties capable of cushioning shear-induced damage. Its porous architecture facilitated accelerated nutrient transport while supporting effective cell adhesion and guiding organized proteoglycan deposition with minimal fibrosis. In vivo evaluation revealed a 30.7% higher MOCART score in the experimental group compared to controls, with mechanical properties closely approximating those of healthy native cartilage.</p><p><strong>Conclusion: </strong>Collagen hydrogels that maintain the triple-helix structure represent a highly promising biomaterial platform for cartilage regeneration, combining excellent biocompatibility, functional mechanical properties, and significant tissue repair capability while effectively addressing the critical challenge of immunogenicity through targeted terminal peptide removal.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":" ","pages":"933-948"},"PeriodicalIF":5.1,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13415418/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148176804","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intratumoral Injectable Click-Crosslinked Hyaluronic Acid Depot for Sustained Gemcitabine Delivery.","authors":"Kyung Eun Son, Yejin Lee, Yejin Kim, Songmin Lee, Yewon Kim, Tae Woong Kang, Kyungsook Kim, Moon Suk Kim","doi":"10.1007/s13770-026-00819-z","DOIUrl":"10.1007/s13770-026-00819-z","url":null,"abstract":"<p><strong>Background: </strong>Gemcitabine (GE) is a widely used chemotherapeutic agent for solid tumors; however, its therapeutic efficacy is often compromised by rapid diffusion from the tumor site and insufficient intratumoral retention following local administration. Injectable hydrogel-based drug depots offer a promising strategy to prolong local drug availability and enhance antitumor efficacy while minimizing systemic toxicity.</p><p><strong>Methods: </strong>An intratumoral injectable, gemcitabine-loaded, click-crosslinked hyaluronic acid hydrogel (GE + Cx-HA) was developed using a bioorthogonal click reaction to enable rapid in situ gelation. Physicochemical properties, gelation behavior, viscoelasticity, and injectability through a fine-gauge needle were characterized. In vitro gemcitabine release profiles and anticancer activity against B16F10 melanoma cells were evaluated. Antitumor efficacy, angiogenesis inhibition, and systemic toxicity were assessed in a murine melanoma model following a single intratumoral injection.</p><p><strong>Results: </strong>GE + Cx-HA remained in a low-viscosity solution state prior to injection and rapidly formed a stable hydrogel depot upon click crosslinking without needle clogging. The crosslinked network significantly suppressed burst release and enabled sustained gemcitabine release in vitro. Compared with free gemcitabine, GE + Cx-HA exhibited prolonged anticancer activity against B16F10 melanoma cells. In vivo, a single intratumoral administration of GE + Cx-HA markedly inhibited tumor growth and angiogenesis for up to 18 days, without observable systemic toxicity.</p><p><strong>Conclusion: </strong>These results demonstrate that GE + Cx-HA functions as an effective intratumoral drug depot, providing sustained local chemotherapy and enhanced antitumor efficacy, highlighting its potential as a localized therapeutic platform for solid tumor treatment.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":" ","pages":"815-831"},"PeriodicalIF":5.1,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13415715/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148228202","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Essential Oils in Skin Tissue Engineering: Opportunities, Integration, and Overcoming Challenges.","authors":"Elif Emekdar, Selcen Ari Yuka, Azime Erarslan","doi":"10.1007/s13770-026-00814-4","DOIUrl":"10.1007/s13770-026-00814-4","url":null,"abstract":"<p><strong>Background: </strong>Essential oils (EOs) derived from plants have been utilized for the development of various approaches in biomedical applications due to their superior properties. In particular, their antimicrobial, anti-inflammatory, antioxidant, and wound-healing effects, alongside their biocompatibility and biodegradability, have made EOs a significant complementary agent in tissue regeneration-focused applications. Initial uses of EOs focused primarily on direct application and evaluation of their therapeutic efficacy; however, these approaches have been limited by issues such as volatility, instability, and potential for irritation.</p><p><strong>Methods: </strong>This review focuses on current perspectives in tissue engineering strategies, based on the biological functions of EO, such as biocompatibility, antimicrobial, anticancer, and antioxidant properties. Based on this comprehensive background of biological functions, current studies addressing nanoparticle systems, smart delivery systems, and wound dressings and coatings have been analyzed to identify existing issues and strategies to tackle these challenges.</p><p><strong>Results: </strong>In skin tissue engineering applications, innovative strategies such as nanoparticle encapsulation, integration into smart delivery systems, and the development of wound dressings containing EO have been developed. These advanced approaches offer advantages such as improved EO stability, controlled release, and enhanced efficacy, while also enriching the biofunctionality of the platform. While advanced delivery systems improve the stability of EOs, long-term stability under physiological and clinical conditions remains challenging. However, compared to conventional methods, these advancements strengthen the potential of EOs to drive tissue repair processes in a more controlled and functional manner.</p><p><strong>Conclusion: </strong>The integration of EO-based tissue engineering with nanotechnology offers a promising approach to optimizing the biological effects of these systems and enhancing the success of their application. Although challenges such as safety, biomaterial interactions, and scalability persist, recent advancements are rapidly overcoming these obstacles. EO-based strategies hold significant potential for overcoming current limitations and advancing the field, particularly in skin tissue engineering.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":" ","pages":"771-789"},"PeriodicalIF":5.1,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13415709/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148472793","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Remote Ischemic Preconditioning Enhances Skin Flap Survival via ZNF667/SDF1-Mediated Endothelial Progenitor Cells Functions for Angiogenesis.","authors":"Yuanbin Li, Jingzhang Li, Zhonglei Liang, Xin Chen, Wei Xiong, Yuhui Huang, Aizhu Qiu, Zhuang Chen, Jianjun Kuang","doi":"10.1007/s13770-026-00817-1","DOIUrl":"10.1007/s13770-026-00817-1","url":null,"abstract":"<p><strong>Background: </strong>Flap transplantation plays a vital role in wound reconstruction. However, the mechanisms by which remote ischemic preconditioning (RIPC) may improve flap survival remain incompletely understood.</p><p><strong>Methods: </strong>Rats were randomly assigned to three groups: sham, ischemia/reperfusion (I/R), and RIPC + I/R. The I/R model was established by ligating the iliopsoas and thoracodorsal arteries to induce flap ischemia, followed by reperfusion. RIPC was performed via limb clamping. A combination of high-throughput sequencing, functional cellular assays, and live imaging was used to assess gene expression, cellular functions, and flap viability.</p><p><strong>Results: </strong>RIPC upregulated the expression of ZNF667. This protein acted as a transcriptional repressor of VHL by binding to its promoter region, where it competitively inhibited the recruitment of histone-modifying enzymes, including MLL3/4, SETD1A, and EP300. Consequently, histone methylation and acetylation were reduced, leading to suppressed VHL transcription. The downregulation of VHL diminished the ubiquitination-mediated degradation of hypoxia-inducible factor-1α (HIF-1α), which in turn enhanced the expression of stromal cell-derived factor 1 (SDF1). This signaling cascade promoted the proliferation, migration, differentiation, and tube-forming capacity of endothelial progenitor cells (EPCs). Live imaging confirmed that RIPC stimulated the recruitment of EPCs into the flap tissue, accompanied by increased microvessel density. These effects collectively enhanced angiogenesis and significantly reduced the area of flap necrosis.</p><p><strong>Conclusion: </strong>RIPC improves flap survival by modulating the ZNF667-VHL-SDF1 axis and augmenting the function of EPCs. These findings not only provide a potential therapeutic strategy for flap transplantation but also advance our understanding of the mechanisms underlying flap survival.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":" ","pages":"881-899"},"PeriodicalIF":5.1,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13415716/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148176793","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"hsa_circ_0008758 Activates the MDM2/FOXO3a/PGK1 Pathway Through the miR-361-3p/SPIN1 Axis to Promote the Warburg Effect of Non-Small Cell Lung Cancer.","authors":"Lei Wei, Fei Xu, Lei Xiong, LeLe Wang, HaiRong Huang, Kang Wang, Jing Luo, Yi Shen, YanQing Wang, Feng Jiang","doi":"10.1007/s13770-026-00816-2","DOIUrl":"10.1007/s13770-026-00816-2","url":null,"abstract":"<p><strong>Background: </strong>The involvement of circRNAs in tumors, such as non-small cell lung cancer (NSCLC), has been established. The objective of this research was to examine the function and regulatory mechanism of hsa_circ_0008758 (circ_0008758) in NSCLC.</p><p><strong>Methods: </strong>The expression of circ_0008758 in NSCLC tissues and cell lines was evaluated by RT-qPCR. Cell proliferation was assessed using the CCK-8 assay and colony formation assay. Apoptosis was evaluated through flow cytometry. Cell migration was measured using the scratch test, while cell invasion was determined using the transwell assay. The Warburg effect was assessed by measuring glucose uptake and lactic acid production using commercially available kits. The targeting relationship between miR-361-3p and circ_0008758 or SPIN1 was confirmed through a bioinformatics website analysis and a dual-luciferase reporter assay. The MDM2/FOXO3a/PGK1 pathway was examined by Western blot analysis.</p><p><strong>Results: </strong>circ_0008758 expression was augmented in NSCLC. Inhibiting circ_0008758 or elevating miR-361-3p resulted in decreased proliferation, migration, invasion, and Warburg effect in NSCLC cells, while promoting cell apoptosis. The opposite effect could be obtained by up-regulating circ_0008758 or down-regulating miR-361-3p. Furthermore, circ_0008758 was found to enhance SPIN1 expression by acting as a sponge for miR-361-3p. Up-regulating SPIN1 counteracted the effects of circ_0008758 down-regulation on NSCLC cells. Additionally, circ_0008758 was found to activate the MDM2/FOXO3a/PGK1 pathway by the miR-361-3p/SPIN1 axis.</p><p><strong>Conclusion: </strong>circ_0008758 promotes the Warburg effect in NSCLC through the miR-361-3p/SPIN1 axis and by activating the MDM2/FOXO3a/PGK1 pathway.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":" ","pages":"867-879"},"PeriodicalIF":5.1,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13415430/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148550485","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mesenchymal Stem Cell-Derived Extracellular Vesicles Attenuate Diabetic β-Cell Apoptosis and Dedifferentiation by Delivering miR-4436.","authors":"Jianbo Xu, Yuntong Sun, Fengtian Sun","doi":"10.1007/s13770-026-00823-3","DOIUrl":"10.1007/s13770-026-00823-3","url":null,"abstract":"<p><strong>Background: </strong>Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by β-cell dysfunction and insulin resistance with limited treatment options. The targeting of pancreatic β-cell apoptosis and dedifferentiation represents a promising approach for T2DM therapy. Recently, mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) have demonstrated repair potential for metabolic diseases. However, the effects of MSC-EVs on β-cell apoptosis and dedifferentiation in T2DM remain largely unclear.</p><p><strong>Methods: </strong>We established db/db mouse model and high glucose-stimulated MIN6 cell model to evaluate the therapeutic efficacy of MSC-EVs in vivo and in vitro. Transcriptome sequencing, proteomic analysis, and microRNA (miRNA) sequencing were applied to explore the molecular mechanism underlying MSC-EV-induced β-cell protection.</p><p><strong>Results: </strong>MSC-EVs significantly mitigated hyperglycemia, improved glucose tolerance, and restored β-cell function by preventing β-cell loss and reducing dedifferentiated β-cell populations in db/db mice. Mechanistically, MSC-EV treatment reversed hyperglycemia-induced ecotropic virus integration site 1 (EVI1) upregulation in β cells, and EVI1 knockdown significantly suppressed β-cell apoptosis and dedifferentiation by promoting forkhead box protein O1 (FOXO1) expression. MiRNA sequencing revealed that miR-4436 enriched in MSC-EVs inhibited EVI1 expression by directly binding to EVI1 mRNA. MiR-4436 knockdown abolished the therapeutic effects of MSC-EVs in T2DM CONCLUSION: MSC-EVs inhibit pancreatic β-cell loss and dedifferentiation by miR-4436-mediated EVI1/FOXO1 regulation. Therefore, MSC-EV administration may represent a promising therapeutic strategy for T2DM.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":" ","pages":"901-915"},"PeriodicalIF":5.1,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13415732/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148340326","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Non-Cytopathic Mammalian Orthoreovirus Infection Triggers Innate Immune Responses in Human Tonsil-Derived Mesenchymal Stem Cells: Implications for Cell Therapy Quality Control.","authors":"Jeong Eun Kim, Ji Yeong Noh, Kyeong Eun Lee, Young Il Lee, Juyun Park, Min Chan Kim, Da Hyeon Choi, Hye Ji Jung, Hee Sung Jung, Jung Won Park, Eun-Ok Lee, Van Thi Lo, Hye Kwon Kim, Yoon Shin Park","doi":"10.1007/s13770-026-00825-1","DOIUrl":"10.1007/s13770-026-00825-1","url":null,"abstract":"<p><strong>Background: </strong>Tonsil-derived mesenchymal stem cells (TMSCs) are widely used in regenerative medicine due to their high proliferative capacity and differentiation potential. However, their origin from immunological gateways exposes them to pathogens, raising concern about viral contamination during cell preparation. Understanding how these pathogens affect the biological and immunological properties of TMSCs is crucial for ensuring the safety and consistency of cell-based therapies. This study evaluated TMSC susceptibility and molecular responses to mammalian orthoreovirus (MRV).</p><p><strong>Methods: </strong>MRV infectivity in TMSCs and the innate immune responses were investigated using RNA-seq. Viral replication was confirmed by viral titration, L1 segment RT-PCR, and transcriptome mapping. Cellular impact was assessed using Live/Dead assays and protein-protein interaction network analysis.</p><p><strong>Results: </strong>TMSCs were infected with MRV strains to evaluate their susceptibility. Although no significant cytopathic effects were observed, the cells exhibited high viral permissivity to MRV, with stable viral titers of 3.9-5.5 log TCID₅₀/ml and positive L1 gene segment RT-PCR. RNA-seq confirmed active replication, with reads successfully mapped to the MRV genome. Transcriptomic profiling showed robust induction of antiviral and stress response genes, including HSPA6, PEG10, OASL, and IFIT2. Gene set enrichment and protein network analyses highlighted enrichment of viral defense pathways and identified IL1B, ISG15, and RSAD2 as key hub genes driving the host inflammatory immune response.</p><p><strong>Conclusion: </strong>MRV establishes a permissive but non-cytopathic infection in TMSCs, triggering innate immune activation through upregulation of IL1B, ISG15, and RSAD2. This virus-induced shift from a quiescent to an immunomodulatory phenotype may compromise therapeutic consistency. Because visual quality control fails to detect latent infections, rigorous viral monitoring during TMSC preparation is essential to ensure safety in clinical applications.</p>","PeriodicalId":23126,"journal":{"name":"Tissue engineering and regenerative medicine","volume":" ","pages":"917-931"},"PeriodicalIF":5.1,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13415725/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148472774","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}