Stem Cells International最新文献

{"title":"miR-1275 Delivered via Mesenchymal Stem Cell-Derived Extracellular Vesicles Regulates ER-Phagy Through AXIN2 in Nucleus Pulposus Cells.","authors":"Zhiwu Dong, Hailong Zhang, Wenwei Yang, Keliang Huang, Xin Zhang, Lianxiang Xing, Ying Zhang, Kewen Zhao","doi":"10.1155/sci/5091529","DOIUrl":"10.1155/sci/5091529","url":null,"abstract":"<p><p>Intervertebral disc degeneration (IDD) is a major contributor to low back pain, a prevalent and debilitating condition. Nucleus pulposus (NP) cells are essential for maintaining disc homeostasis, and their dysfunction plays a crucial role in IDD development. This study aimed to explore the potential role of miR-1275, delivered via mesenchymal stem cell-derived extracellular vesicles (MSCs-EVs), in IDD pathogenesis and to elucidate the underlying molecular mechanisms through <i>in vitro</i> investigations. Decreased miR-1275 expression and elevated endoplasmic reticulum (ER) stress were observed in degenerated human NP tissues compared to normal controls. An <i>in vitro</i> IDD model was established by treating NP cells (NPCs) with advanced glycation end products (AGEs). Subsequent experiments demonstrated that EVs from miR-1275-overexpressing MSCs reduced AGE-induced ER stress, extracellular matrix (ECM) degradation, and apoptosis in NPCs by enhancing ER-phagy. Bioinformatic analyses identified AXIN2 as a direct target of miR-1275. Remarkably, AXIN2 overexpression significantly attenuated the effects of miR-1275 on NPC proliferation, apoptosis, ER stress, and ER-phagy under AGE-induced conditions. Mechanistic studies validated AXIN2 as a target of miR-1275, with miR-1275 binding to the 3' untranslated region of AXIN2 and regulating its expression. Collectively, our <i>in vitro</i> findings reveal that MSCs-EVs carrying miR-1275 can modulate ER stress and enhance ER-phagy in NPCs through the targeted downregulation of AXIN2, suggesting a potential molecular mechanism in IDD pathogenesis.</p>","PeriodicalId":21962,"journal":{"name":"Stem Cells International","volume":"2025 ","pages":"5091529"},"PeriodicalIF":3.8,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12140824/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144235288","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcription Factor SOX10 Improves Migration and Homing of MSCs After Myocardial Infarction by Upregulating CXCR4.","authors":"Baoping Deng, Qili Liu, Jiemin Yang, Jing Xu, Hongmei Zheng, Weiping Deng","doi":"10.1155/sci/1880402","DOIUrl":"10.1155/sci/1880402","url":null,"abstract":"<p><p><b>Background:</b> CXCR4 enhances the homing of mesenchymal stem cells (MSCs), thereby potentially improving outcomes in myocardial infarction (MI). However, the molecular mechanisms underlying MSC homing remain poorly understood. <b>Methods:</b> The identity of MSCs was confirmed through flow cytometry, utilizing their cluster of differentiation (CD) marker profile. Migration and invasion were assessed using wound healing and transwell assays. In a rat MI model, myocardial function, hemodynamic parameters, and the degree of myocardial fiber damage were evaluated post-MSC treatment, along with the observation of MSC homing. Luciferase assays identified binding sites between SOX10 and the CXCR4 promoter, and the effects of SOX10 on MSC migration, invasion, and homing were explored both <i>in vitro</i> and <i>in vivo</i>. <b>Results:</b> Overexpression of CXCR4 significantly enhanced MSC migration, invasion, and homing. MSCs overexpressing CXCR4 improved cardiac function and reduced infarct size in the rat MI model. A direct interaction between SOX10 and CXCR4 was confirmed, with SOX10 acting as a transcription factor to upregulate CXCR4 expression, thereby enhancing MSC homing and ameliorating MI in rats. Knockdown of SOX10 reversed the beneficial effects of CXCR4-overexpressing MSCs on MI therapy, as well as the functional impact of CXCR4 on MSCs. <b>Conclusion:</b> In conclusion, SOX10 facilitates MSC homing by upregulating CXCR4 expression, offering a potential therapeutic approach for MI treatment.</p>","PeriodicalId":21962,"journal":{"name":"Stem Cells International","volume":"2025 ","pages":"1880402"},"PeriodicalIF":3.8,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12129602/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144209555","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mixtures of PRR Ligands Partly Mimic the Immunomodulatory Response of <i>γ</i>i <i>Staphylococcus aureus</i>, Enhancing Osteogenic Differentiation of Human Mesenchymal Stromal Cells.","authors":"Paree Khokhani, Kelly Warmink, Moyo Kruyt, Harrie Weinans, Debby Gawlitta","doi":"10.1155/sci/1445520","DOIUrl":"10.1155/sci/1445520","url":null,"abstract":"<p><p>Recent evidence indicates the potential of gamma-irradiated (<i>γ</i>i) <i>Staphylococcus aureus</i> to be used as an osteo-immunomodulator for bone regeneration. This study aims at characterizing the inflammatory milieu caused by the stimulation of <i>γ</i>i <i>S. aureus</i> in immune cells and investigates its effects on MSC osteogenic differentiation. Furthermore, we aimed to recreate the immune-modulatory response exhibited by <i>γ</i>i <i>S. aureus</i> by using a mixture of various synthetic pathogen recognition receptor (PRR) ligands consisting of TLR2, TLR8, TLR9, and NOD2 agonists. Human peripheral blood mononuclear cells (hPBMCs), isolated from healthy human donors, were exposed to <i>γ</i>i <i>S. aureus</i> or seven different ligand mixtures. After 24 h, the conditioned medium (CM) from the hPBMCs was collected and its effects on hMSC osteogenic differentiation were investigated by assessing alkaline phosphatase (ALP) activity and matrix mineralization. The hPBMCs and their CM were also analyzed by bulk RNA sequencing and for cytokine secretion. CM from the <i>γ</i>i <i>S. aureus</i> and the mixture consisting of Pam3CSK4, C-class CpG oligodeoxynucleotide (CpG ODN C), and murabutide targeting TLR2, TLR9, and NOD2 showed a fivefold increase in ALP and matrix mineralization in a donor-dependent manner. These effects were due to the upregulation of inflammatory signaling pathways, which led to an increase in cytokines and chemokines TNF, interleukin (IL)-6, IFN-<i>γ</i>, IL-1<i>α</i>, CXCL10, CCL18, CCL17, CXCL1, and CCL5. Upregulation of genes like BMP2R, BMP6R, BGLAP, and others contributed to the upregulation of osteogenic pathways in the hPBMCs stimulated with <i>γ</i>i <i>S. aureus</i> and the aforementioned mix. Thus, formulations with mixtures of PRR ligands may serve as immune-modulatory osteogenesis-enhancing agents.</p>","PeriodicalId":21962,"journal":{"name":"Stem Cells International","volume":"2025 ","pages":"1445520"},"PeriodicalIF":3.8,"publicationDate":"2025-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12127128/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144209554","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Overexpression of Decorin Optimizes the Treatment Efficacy of Umbilical Cord Mesenchymal Stem Cells in Bleomycin-Induced Pulmonary Fibrosis in Rats.","authors":"Yaofeng Zhi, Minghui Shu, Pingsheng Tang, Yingjie Li, Min Guo, Jiongrui Deng, Haixin Mo, Meimei Wu, Baoyi Liu, Yanyang Mai, Jie Ling, Xulin Zhao, Xin Zhang, Wanli Zuo","doi":"10.1155/sci/6324980","DOIUrl":"10.1155/sci/6324980","url":null,"abstract":"<p><p>Idiopathic pulmonary fibrosis (IPF) is a long-term, diffuse pulmonary parenchyma lesion that primarily affects middle-aged and older adults. It is characterized by pulmonary interstitial fibrosis of unknown cause. The death rate upon diagnosis is higher than that of many other cancer types. Mesenchymal stem cell (MSC) treatment of organ fibrosis is a hot topic in preclinical and clinical research because it effectively treats IPF. In recent years, decorin (DCN) has been regarded as a critical mediator for its anti-inflammatory and antifibrotic effects. The purpose of this study was to generate human umbilical cord MSCs (HUC-MSCs) that overexpress DCN and to investigate the safety, mechanism, and effectiveness of using these cells to cure pulmonary fibrosis caused by bleomycin (BLM). First, lentiviral (LV) particles carrying the therapeutic DCN gene (LV-DCN) and control LV particles were created and transfected using the plasmid vector GV208 to create a viral solution for infecting HUC-MSCs. These solutions were used to create a DCN overexpression cell line and an MSC-Con. cell line infected with the control lentivirus. Intratracheal injection of BLM was used to establish a rat model of pulmonary fibrosis. On the second day following modeling, different treatments were administered, and the body weight and survival status of the rats were noted. The relevant tests were performed on days 15 and 29 following modeling. The results demonstrated that the overexpression of DCN did not affect the properties of HUC-MSCs and that these cells were effective in treating IPF. MSC-Con. and MSC-DCN reduced systemic inflammation by reducing serum interleukin (IL) 1<i>β</i>. Both cell types successfully treated pulmonary fibrosis in rats, as demonstrated by hematoxylin and eosin (HE) and Masson staining. MSC-DCN showed better efficacy due to lower mortality, higher weight gain, less alveolar inflammation, and less fibrosis. The safety of venous transplantation with MSCs was established by HE staining of the heart, liver, spleen, and kidney, as well as serum lactate dehydrogenase (LDH), creatinine (CRE), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) levels. Immunohistochemical (IHC) staining of CD68 and CD206 in lung tissue and in vitro experiments on THP-1-induced M2 macrophage polarization and transforming growth factor-beta 1 (TGF-<i>β</i>1)-induced MRC-5 fibrosis indicated that MSC-DCN may mitigate lung inflammation by altering macrophage recruitment and polarization and inhibiting TGF-<i>β</i>1 expression to reduce fibrous hyperplasia and collagen deposition, thereby improving the treatment of BLM-induced IPF.</p>","PeriodicalId":21962,"journal":{"name":"Stem Cells International","volume":"2025 ","pages":"6324980"},"PeriodicalIF":3.8,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12119169/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144175021","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of Bariatric Surgery-Related Weight Loss on the Characteristics, Metabolism, and Immunomodulation of Adipose Stromal/Stem Cells in a Follow-Up Study.","authors":"Amna Adnan, Miia Juntunen, Tuula Tyrväinen, Minna Kelloniemi, Laura Kummola, Reija Autio, Mimmi Patrikoski, Susanna Miettinen","doi":"10.1155/sci/1212255","DOIUrl":"10.1155/sci/1212255","url":null,"abstract":"<p><p><b>Background:</b> The success of adipose stromal/stem cell (ASC)-based therapies may depend on donor characteristics such as body mass index (BMI). A high BMI may negatively impact the therapeutic potential of ASCs, but the effects of weight loss on ASC-mediated immunoregulation have not been extensively studied. <b>Methods:</b> ASCs were obtained from donors with obesity (obASCs) undergoing bariatric surgery and from the same donors after weight loss (wlASCs). Plasma samples, adipose tissue histology, and ASC characteristics, such as mitochondrial respiration and inflammatory factors, were studied before and after weight loss. The immunomodulatory capacity of ob/wlASCs was evaluated in cocultures with prepolarized and preactivated proinflammatory (M1) and anti-inflammatory (M2) macrophages by determining macrophage surface markers, gene expression, and cytokine secretion. <b>Results:</b> Weight loss significantly decreased plasma leptin levels and increased adiponectin levels. After weight loss, crown-like structures (CLSs) were undetectable, and the adipocyte size decreased. Weight loss significantly improved mitochondrial respiration in ASCs and resulted in a notable increase in their proliferative capacity. The proinflammatory marker genes tumor necrosis factor alpha (<i>TNF-α</i>), chemokine ligand 5 (<i>CCL5</i>), and cyclooxygenase-2 (<i>COX2</i>), as well as the proinflammatory cytokine interleukin 12p70 (IL-12p70), were significantly downregulated, while the anti-inflammatory gene tumor necrosis factor-inducible gene 6 (<i>TSG6</i>) was also significantly downregulated in ASC monocultures after weight loss. Following weight loss, ASCs exhibited increased proinflammatory properties when cocultured with macrophages, characterized by the downregulation of anti-inflammatory factors, along with the upregulation of several proinflammatory factors, compared with the effects of macrophage monocultures. Conversely, wlASCs demonstrated improved immunosuppressive functions in coculture with macrophages, as indicated by the upregulation of <i>TSG6</i> gene expression and interleukin 4 (IL-4) secretion. <b>Conclusions:</b> Weight loss improved donors' metabolic health and partially recovered ASCs' anti-inflammatory gene expression and cytokine secretion profiles in monocultures. However, it was inadequate to fully restore the immunosuppressive functions of ASCs in cocultures with macrophages. Therefore, not only donor BMI but also weight loss history, among other donor characteristics, might be considered for optimal ASC-based therapy.</p>","PeriodicalId":21962,"journal":{"name":"Stem Cells International","volume":"2025 ","pages":"1212255"},"PeriodicalIF":3.8,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12092157/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144111858","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spatio-Temporal Regulation of IGFs in Enamel Development: Molecular Mechanisms From Ameloblast Polarity to Mineralization Homeostasis.","authors":"Xue Zeng, Pengcheng He","doi":"10.1155/sci/9665706","DOIUrl":"10.1155/sci/9665706","url":null,"abstract":"<p><p>The development of enamel relies on the precise regulation of ameloblast differentiation, enamel matrix secretion, and mineralization. The formation of enamel is crucial for the normal function of dental tissues, and promoting enamel remineralization is of significant importance for the treatment of dental caries. Understanding the underlying mechanisms of enamel development is essential for oral therapy and provides a bridge to tooth regeneration. Among various growth factors, the insulin-like growth factor (IGF) family, including IGF-1 and IGF-2, has been shown to play a key role in enamel formation by activating signaling pathways such as PI3K/AKT and MAPK. This review summarizes the role of the IGF family in tooth development and enamel formation and sheds light on key parts of the research for future treatment improvements.</p>","PeriodicalId":21962,"journal":{"name":"Stem Cells International","volume":"2025 ","pages":"9665706"},"PeriodicalIF":3.8,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12092154/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144111910","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tenogenic Cues Are Biochemically and Environmentally Distinct for Tendon Stem Cells and Mesenchymal/Stromal Stem Cells.","authors":"Vera Citro, Marta Clerici, Giovanna Della Porta, Nicola Maffulli, Aldo R Boccaccini, Tina P Dale, Nicholas R Forsyth","doi":"10.1155/sci/9047956","DOIUrl":"10.1155/sci/9047956","url":null,"abstract":"<p><p>Tendon tissue engineering draws on regenerative medicine principles, offering innovative solutions to address the challenges posed by tendon injuries and degenerative conditions. Tendons' inherent limited regenerative capacity often hinders complete recovery from injuries, leading to chronic conditions and impaired functionality. Autologous mesenchymal/stromal stem cells (MSCs) and tendon-derived stem cells (TSCs), combined with growth factors (GFs) like GDF-5, GDF-6 and GDF-7, are emerging as potential therapies for tendinopathy. These GFs are crucial for tendon development and promoting tenogenic differentiation, though the exact pathways they activate remain unclear. For this reason, directly comparing all three pathways to assess their impact on both MSCs and TSCs is essential. This study examined the effects of GDF-5, GDF-6 and GDF-7 on tenogenic differentiation in MSCs and TSCs, with a focus on how oxygen levels (21% O₂ vs. physoxia at 2% O₂) influence this process. The expression profiles of key tenogenic genes (Scleraxis [Scx], Tenomodulin [Tnmd], Thrombospondin-4 [Thromb-4] and Tenascin-C [Tnc-C]) were explored by quantitative reverse transcription PCR (RT-qPCR) following supplementation with individual GFs. Transcriptional analysis was complemented by Tnmd immunofluorescence (IF) and image analysis to identify optimal differentiation parameters. The study highlighted GDF-7 as a powerful inducer of tenocyte-like cell differentiation in MSCs, showcasing sustained expression of tenogenic genes over time in 21% O₂. Moreover, TSCs in physoxia differentiate into tenocytes without an additional GF requirement. In conclusion, the study lays a foundation for understanding the complex interplay of GFs, oxygen levels and cellular responses in the quest for tendon regeneration. In doing so, it establishes that different cell types have differing biochemical requirements for induction of tenogenic differentiation. While offering promising avenues for tissue engineering platforms, it underscores the need for further research to fully harness the potential of MSCs and TSCs in vivo for tendon regeneration.</p>","PeriodicalId":21962,"journal":{"name":"Stem Cells International","volume":"2025 ","pages":"9047956"},"PeriodicalIF":3.8,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12092158/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144111941","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcriptome and Proteome Analysis Identify Decorin as a Principal Antifibrotic Component Trapping TGF-<i>β</i>1 Within Adipose-Derived Stem Cell Secretome.","authors":"Lin Kang, Zhujun Li, Fangyuan Li, Ziming Li, Liquan Wang, Tianhao Li, Jieyu Xiang, Songlu Tseng, Nanze Yu, Jiuzuo Huang, Xiao Long","doi":"10.1155/sci/1416567","DOIUrl":"10.1155/sci/1416567","url":null,"abstract":"<p><p>Adipose-derived stem cells (ADSCs) demonstrated therapeutic potential in various fibrotic diseases, with their paracrine proteins playing a crucial role. Nonetheless, the principal paracrine factors of ADSCs responsible for antifibrosis have not yet been well identified. To address this issue, we initially confirmed that ADSCs could attenuate fibrosis and suppress TGF-<i>β</i>1 in bleomycin-induced skin fibrosis mouse models. RNA-sequencing of the cocultured fibroblasts demonstrated that ADSCs effectively inhibited the TGF-<i>β</i>/Smad2 signaling pathway in fibroblasts through the paracrine approach. Proteomic analysis of the cell supernatant (CS) demonstrated a significant upregulation of 97 proteins in the secretome of ADSCs, among which decorin (DCN) exhibited a particularly elevated level of overexpression. Protein-protein interaction (PPI) network analysis indicated a strong correlation between DCN and TGF-<i>β</i>1, with DCN effectively trapping TGF-<i>β</i>1 through core protein binding. Cell experiments demonstrated that DCN could effectively inhibit TGF-<i>β</i>1-induced fibroblast proliferation. Therefore, it was concluded that DCN was a crucial protein in ADSC secretome that exerted antifibrotic effects by inhibiting TGF-<i>β</i>1. This study conducted an in-depth insight into the paracrine function of ADSCs through transcriptome and proteome analysis, identifying DCN as an essential paracrine factor mediating the antifibrotic effect of ADSCs, which could provide valuable theoretical support for the use of ADSC secretions as well as DCN in the treatment of fibrotic diseases.</p>","PeriodicalId":21962,"journal":{"name":"Stem Cells International","volume":"2025 ","pages":"1416567"},"PeriodicalIF":3.8,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12084782/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144094821","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impacts of Circular RNAs on the Osteogenic Differentiation of Dental Stem Cells.","authors":"Yang Wang, Meijie Tu, Huihui Gao, Shuli Deng","doi":"10.1155/sci/8338337","DOIUrl":"https://doi.org/10.1155/sci/8338337","url":null,"abstract":"<p><p>Dental stem cells are widely viewed as good options for bone regeneration because of their ease of acquisition, innate ability to renew themselves, and ability to differentiate into different types of cells. However, the process of osteogenic differentiation of dental stem cells is orchestrated by an intricate system of regulatory mechanisms. Recent studies have demonstrated the critical impacts of circular RNAs (circRNAs) on osteogenic differentiation of dental stem cells. Exploring the roles and regulatory pathways of circRNAs in dental stem cells could identify novel targets and approaches for utilizing dental stem cell therapy in clinical settings. This review provides a comprehensive overview of the functions and mechanisms of circRNAs, with a particular focus on their expression patterns and regulatory roles in osteogenic differentiation of various dental stem cell types. Furthermore, this review discusses current research challenges in this field and proposes future directions for advancing our understanding of circRNA-mediated regulation in dental stem cell biology.</p>","PeriodicalId":21962,"journal":{"name":"Stem Cells International","volume":"2025 ","pages":"8338337"},"PeriodicalIF":3.8,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12081154/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144080498","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunological Safety Evaluation of Exosomes Derived From Human Umbilical Cord Mesenchymal Stem Cells in Mice.","authors":"Cancan Wang, Xinmei Hu, Yu Liu, Yu Xiao, Peng Jiang, Yunjing Lin, Xiaomin Liu, Zhengmian Zhang, Liang-Cheng Li, Zhongquan Qi","doi":"10.1155/sci/9986368","DOIUrl":"https://doi.org/10.1155/sci/9986368","url":null,"abstract":"<p><p>Mounting evidence indicates that exosomes derived from human umbilical cord mesenchymal stem cells (hucMSCs-exosomes) combine the advantages of hucMSC pluripotency with their nanoscale dimensions, enhancing their clinical potential through prolonged circulation half-life. Despite these promising characteristics, research on their immunological toxicity remains insufficient. This study focuses on the impact of hucMSC-exosomes on the general toxicity and immunopathological indicators. When mice received tail vein injections of 6 × 10¹⁰ hucMSC-exosomes particles, we observed no significant changes in body weight, feed intake, blood composition, organ indices, or histopathological findings throughout the 14 days observation period. Similarly, blood levels of immunoglobulins, cytokines, and lymphocyte subpopulations remained stable. The hucMSC-exosomes produced no detectable negative effects on immune organs including the thymus, spleen, and bone marrow. These findings indicate that intravenous administration of 6 × 10¹⁰ particles of hucMSC-exosomes appears relatively safe at the murine level. This assessment of safety and immunological impact following intravenous hucMSC-exosomes infusion offers experimental support for potential clinical applications and future analyses in this field.</p>","PeriodicalId":21962,"journal":{"name":"Stem Cells International","volume":"2025 ","pages":"9986368"},"PeriodicalIF":3.8,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12049250/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144034751","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}