Stem Cells International最新文献

{"title":"Stromal Vascular Fraction Gel for Osteoarthritis: Mechanisms and Therapeutic Benefits.","authors":"Runze Zhang, Yuanhang Yang, Wanli Gao, Xing Lei, Xin Yin, Wei Zhang, Ling Zhang, Yunqi Zhang, Maohua Chen, Junjun Yang, Lisheng Wu","doi":"10.1155/sci/8316087","DOIUrl":"10.1155/sci/8316087","url":null,"abstract":"<p><p>Osteoarthritis (OA), a prevalent degenerative joint disorder, is suboptimally managed by existing treatments owing to adverse effects, limited therapeutic efficacy, and the inability to achieve genuine cartilage repair. Adipose-derived stromal vascular fraction (SVF)-gel, which is abundant in stem cells and bioactive factors, has an autologous origin and favorable immunocompatibility and exhibits favorable safety and efficacy in facilitating cartilage regeneration and repair. Building upon prior research, this review discusses the clinical efficacy and potential of SVF-gel, while also recognizing challenges such as the standardization of preparation procedures and dosage optimization. Future research ought to concentrate on integrating advanced technologies, including gene editing, artificial intelligence (AI), and nanomaterials, to drive its development towards more precise and personalized therapeutic approaches.</p>","PeriodicalId":21962,"journal":{"name":"Stem Cells International","volume":"2026 ","pages":"8316087"},"PeriodicalIF":3.6,"publicationDate":"2026-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13522831/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148851367","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":"SIAH1-Mediated Ubiquitination and Degradation of TRIB3 Modulate Osteogenic and Adipogenic Differentiation.","authors":"Hao Lv, Hairu Yi, Yinghao Zhu, Yan Wang, Yuxiang Yang, Xingyu Wang, Long Liang, Jiuxiang Wang, Ting Jiang","doi":"10.1155/sci/5507620","DOIUrl":"10.1155/sci/5507620","url":null,"abstract":"<p><strong>Background: </strong>The imbalance between osteogenic and adipogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) is a key factor in osteoporosis (OP). TRIB3 acts as a molecular switch regulating this process. While E3 ubiquitin ligases are known to influence TRIB3 protein stability, the specific role of E3 ligase-mediated TRIB3 ubiquitination in directing BMSCs' fate remains unclear. This study systematically investigates this mechanism.</p><p><strong>Methods: </strong>We first predicted potential E3 ubiquitin ligases for TRIB3 using the UbiBrowser database. Differentially expressed E3 ligases were then screened from the GEO datasets. Molecular docking with the TRIB3 protein identified the candidate with the highest binding affinity for a mechanistic study. Serum samples from osteoporotic patients and healthy controls were analyzed to verify clinical correlation. For in vivo validation, we performed in vivo rescue experiments in naturally aged osteoporotic mice using femoral injection of SIAH1-knockdown lentivirus. Immunohistochemistry, immunofluorescence, and western blot were used to assess the expression of TRIB3 and SIAH1. In vitro, we overexpressed or knocked down SIAH1 to examine its effects on TRIB3 ubiquitination, protein stability, and BMSCs differentiation. TRIB3 rescue assays were performed to confirm the dependency.</p><p><strong>Results: </strong>UbiBrowser analysis identified eight E3 ubiquitin ligases targeting TRIB3. Subsequent screening selected SIAH1 for mechanistic investigation. In aged osteoporotic mice and osteoporotic patients, SIAH1 expression was significantly increased, while TRIB3 was decreased. In vivo rescue experiments showed that local knockdown of SIAH1 restored TRIB3 expression, improved bone mineral density (BMD), trabecular microarchitecture, and rebalanced osteogenic and adipogenic differentiation. In vitro, upregulating SIAH1 promoted TRIB3 ubiquitination and proteasomal degradation, reducing TRIB3 protein levels, downregulating osteogenic markers, and upregulating adipogenic markers. Knocking down SIAH1 yielded the opposite effects. TRIB3 overexpression or knockdown fully reversed the effects of SIAH1 on BMSC differentiation.</p><p><strong>Conclusion: </strong>SIAH1 promotes the ubiquitination and proteasomal degradation of TRIB3, thereby disrupting the osteogenic-adipogenic balance of BMSCs and contributing to age-related bone loss. Local inhibition of SIAH1 stabilizes TRIB3 and ameliorates OP. These findings provide a scientific basis and novel therapeutic target for regulating BMSCs differentiation and treating age-related OP via the SIAH1-TRIB3 axis.</p>","PeriodicalId":21962,"journal":{"name":"Stem Cells International","volume":"2026 ","pages":"5507620"},"PeriodicalIF":3.6,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13519890/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148841084","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":"Adipose-Derived Mesenchymal Stem Cells Reduce miR-214-5p to Promote Ovarian Cancer Progression via the β-Catenin Pathway by Targeting PAX8.","authors":"Ningxia Sun, Jing Wang, Hanxu Yang, Xiangyu Liu, Yijing Chu","doi":"10.1155/sci/7152310","DOIUrl":"https://doi.org/10.1155/sci/7152310","url":null,"abstract":"<p><strong>Background: </strong>Building on our previous work, we found that human omental adipose-derived mesenchymal stem cells (ADSCs) promote ovarian cancer growth and metastasis by inducing PAX8, a key oncogenic transcription factor in ovarian cancer. TAZ is a core downstream effector of the Hippo signaling pathway, closely associated with malignant progression in multiple tumors, and our prior work confirmed that PAX8 can stabilize TAZ protein. In this study, we aimed to further clarify how ADSCs regulate PAX8 to explore the downstream signaling pathway driving malignant progression in ovarian cancer.</p><p><strong>Materials and methods: </strong>Ovarian cancer cells were treated with ADSC-conditioned medium (ADSC-CM) to investigate the regulatory effect of ADSCs on miR-214-5p expression. qRT-PCR and western blot were applied to detect the levels of miR-214-5p, PAX8, β-catenin, and TAZ, so as to dissect the regulatory relationship of ADSCs/miR-214-5p/PAX8/β-catenin/TAZ. A dual-luciferase reporter assay verified the direct targeting interaction between miR-214-5p and PAX8. CCK-8 and Transwell invasion assays were conducted to assess the biological functions of the miR-214-5p/PAX8 axis in ovarian cancer progression.</p><p><strong>Results: </strong>We show that ADSC treatment significantly downregulated miR-214-5p in ovarian cancer cells. Moreover, PAX8 is a direct target of miR-214-5p: knockdown or overexpression of miR-214-5p altered PAX8 expression by directly binding to PAX8 mRNA. Additionally, PAX8 stabilizes TAZ by activating the β-catenin pathway. Functionally, miR-214-5p inhibited ovarian cancer cell proliferation and invasion by downregulating PAX8.</p><p><strong>Conclusion: </strong>Taken together, ADSCs downregulate miR-214-5p to increase PAX8 expression, which sequentially activates the β-catenin pathway and stabilizes TAZ. This novel signaling axis is responsible for ADSC-induced ovarian cancer growth and metastasis.</p>","PeriodicalId":21962,"journal":{"name":"Stem Cells International","volume":"2026 ","pages":"7152310"},"PeriodicalIF":3.6,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13490915/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148797991","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":"Comprehensive Preclinical Safety Evaluation of Clinical-Grade hESC-Derived Multipotent Mesenchymal Stem Cells for Interstitial Cystitis.","authors":"Jeong Min Shin, Ah Reum Kang, Dong Seol Gwak, Su Jin Kim, Jin Won Seo, Eun-Young Kim, Ki-Sung Hong, Se-Pill Park, Hyung-Min Chung","doi":"10.1155/sci/5539154","DOIUrl":"https://doi.org/10.1155/sci/5539154","url":null,"abstract":"<p><p>Human embryonic stem cell (hESC)-derived multipotent mesenchymal stem cells (MMSCs) offer therapeutic potential for interstitial cystitis (IC); however, safety concerns, such as tumorigenicity from residual undifferentiated hESCs, must be thoroughly addressed. To address these concerns, we conducted comprehensive in vitro and in vivo safety assessments of clinical-grade MMSCs. Flow cytometry, qRT-PCR, and/or RNA sequencing confirmed the absence of pluripotency markers, including <i>OCT3/4</i>, <i>TRA-1-60</i>, <i>TRA-1-81</i>, and <i>NANOG</i>, in MMSCs. In good laboratory practice (GLP)-compliant studies, BALB/c-<i>nu/nu</i> immunodeficient mice received a single intra-detrusor muscle injection of MMSCs. No adverse clinical signs or immune responses were observed at doses corresponding to up to 6 × 10⁹ cells in humans, the maximum feasible clinical dose based on body weight conversion. Furthermore, no tumor formation was detected for up to 52 weeks following either intra-detrusor muscle or subcutaneous administration. Spiking studies showed teratoma formation only when undifferentiated hESCs exceeded 1%, supporting the absence of tumorigenic risk in the final MMSC product. Biodistribution analyses revealed that MMSCs remained localized at the injection site and were cleared from major organs within 10 days. These findings indicate that MMSCs contain no detectable hESCs within the sensitivity limits of the assays, exhibit no immunogenicity or tumorigenic potential, and are safe for intra-detrusor muscle administration, supporting their clinical application as a cell-based therapy for IC.</p>","PeriodicalId":21962,"journal":{"name":"Stem Cells International","volume":"2026 ","pages":"5539154"},"PeriodicalIF":3.6,"publicationDate":"2026-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13484282/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148797971","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":"Role of Interleukin-10 Overexpressing Mesenchymal Stem Cells in Promoting Bone Marrow Functional Recovery in Aplastic Anemia Mice.","authors":"Qinglin Mo, Lixuan Chen, Yingnan Wu, Zhaolin Chen, Fangfang Lin, Yang Xiao, Zenghui Liu","doi":"10.1155/sci/2300675","DOIUrl":"10.1155/sci/2300675","url":null,"abstract":"<p><strong>Background: </strong>Mesenchymal stem cells (MSCs) are multipotent, nonhematopoietic progenitors capable of supporting hematopoiesis and regulating immunity. Clinical studies have shown that MSCs can aid hematopoietic recovery and balance T helper 17 (Th17) and Treg cells in some aplastic anemia (AA) patients refractory to immunosuppressive therapy (IST). However, full clinical efficacy remains unachieved. To enhance MSC immune regulation while ensuring safety, previous research found interleukin-10 (IL-10), an immunosuppressive factor, can boost MSC function. In this study, we used lentiviral transduction to induce IL-10 gene overexpression in human umbilical cord-derived MSCs and validated their efficacy and safety in AA mouse models.</p><p><strong>Methods: </strong>MSCs were isolated from umbilical cords and genetically modified via lentiviral transduction to overexpress IL-10, generating OEIL10-MSCs. Empty vector plasmids (pCDH-CMV-MCS-EF1-copGFP) were transduced into MSC to create PCDH-MSCs. Both in vitro and in vivo experiments were conducted to investigate their functional changes and mechanisms. Mouse models of nonsevere AA (NSAA) and severe AA (SAA) were established and treated with OEIL10-MSCs or control PCDH-MSCs. The therapeutic efficacy of OEIL10-MSCs in AA was evaluated by assessing blood cell counts, Th17/Treg ratios, and bone marrow histopathology in an AA mouse model. Safety was assessed through liver and kidney function tests.</p><p><strong>Results: </strong>In vitro experiments verified that OEIL10-MSCs exhibited enhanced proliferation capacity, improved anti-inflammatory ability, and reduced oxidative stress levels. In NSAA mouse models, OEIL10-MSCs were more effective in restoring hematopoietic function and elevating Treg cell proportions. In contrast, in SAA mouse models, OEIL10-MSCs demonstrated superior efficacy in elevating red blood cell (RBC) levels and reducing DNA damage compared to PCDH-MSCs.</p><p><strong>Conclusion: </strong>Overexpression of IL-10 may enhance the efficacy of MSCs in treating AA, presenting a promising therapeutic strategy for the clinical application of MSCs.</p>","PeriodicalId":21962,"journal":{"name":"Stem Cells International","volume":"2026 ","pages":"2300675"},"PeriodicalIF":3.6,"publicationDate":"2026-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13464113/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148726872","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":"A Novel Cellular Therapy for Preterm Complications: Safety Profile of Allogeneic Cord Blood Mononuclear Cells in a Pilot Clinical Study.","authors":"Jia Chen, Yabo Mei, Liu He, Zhenlan Du, Guosheng Xing, Xue Du, Liping Cheng, Xiaofei Wei, Danhua Zhao, Yanan Gu, Qiuping Li, Zhichun Feng","doi":"10.1155/sci/9979914","DOIUrl":"10.1155/sci/9979914","url":null,"abstract":"<p><strong>Background: </strong>Preclinical evidence supports the potential use of human umbilical cord blood-derived mononuclear cells (hUCB-MNCs) for preterm infants with preterm birth-associated complications (PBAC). Allogeneic hUCB-MNCs could extend this therapeutic option to infants without autologous cord blood available at birth.</p><p><strong>Methods: </strong>This phase I, open-label, single-arm, and single-center study enrolled 10 preterm infants (gestational age [GA] 27.1 ± 0.7 weeks) with two or more PBAC. All received a single intravenous infusion of allogeneic, partially or fully human leukocyte antigen (HLA)-mismatched hUCB-MNCs without preconditioning or immunosuppression. The median cell was (3.51 ± 0.93) × 10⁶ cells/kg. Safety, adverse events, and clinical outcomes were assessed over a 2-year follow-up period.</p><p><strong>Results: </strong>All infants survived intensive care unit discharge. Four infants were lost to follow-up for parental reasons, with no in-hospital adverse events noted, their long-term outcomes remain unconfirmed. No infusion-related adverse events, acute reactions, or graft-versus-host disease (GVHD) were detected. One case of cerebral palsy was diagnosed during follow-up and was unrelated to cell infusion. Five of the six infants with evaluable long-term data had no respiratory, developmental, or neurological complications. Plasma inflammatory cytokines exhibited exploratory changes after infusion, without confirmed causality. All infants with follow-up data reached age-appropriate growth at 12 and 24 months of corrected age.</p><p><strong>Conclusions: </strong>No major infusion-related adverse events were observed in preterm infants with PBAC receiving allogeneic hUCB-MNC infusion. Six infants completed 2-year follow-up and four were lost to follow-up. Constrained by small sample size and attrition, the results need further verification in larger controlled trials.</p><p><strong>Trial registration: </strong>Chinese Clinical Trial Registry: ChiCTR-OPN-15006932, ChiCTR2000035227.</p>","PeriodicalId":21962,"journal":{"name":"Stem Cells International","volume":"2026 ","pages":"9979914"},"PeriodicalIF":3.6,"publicationDate":"2026-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13464116/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148721494","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":"Mesenchymal Stem Cells Modulate Regulatory T Cells: From Molecular Mechanisms to Disease Therapy.","authors":"Meng Yuan, Ting Sun, Yaru Qiao, Peter Muro, Bo Wang, Xiangjun Zhou, Fei Mao","doi":"10.1155/sci/6457805","DOIUrl":"10.1155/sci/6457805","url":null,"abstract":"<p><p>Mesenchymal stem cells (MSCs) and regulatory T cells (Tregs) form a key immunoregulatory axis essential for maintaining immune homeostasis and treating autoimmune diseases, transplant rejection, and inflammatory disorders. Although both MSCs and Tregs have been individually studied, a clear synthesis of how MSCs regulate Treg function across distinct mechanistic layers and disease contexts remains lacking. MSCs regulate Treg differentiation, expansion, and functional stability through paracrine signaling, intercellular contact-dependent pathways, extracellular vesicle (EV)-mediated transfer of microRNAs (miRNAs) and proteins, mitochondrial transfer, and metabolic and epigenetic reprogramming. These mechanisms restore Th17/Treg balance, suppress inflammation, and promote tissue repair. Preclinical studies demonstrate strong therapeutic potential in multiple immune-mediated diseases; however, clinical translation remains limited. Unlike previous studies, this review integrates soluble and exosomal signaling pathways, compares shared and disease-specific regulatory mechanisms, and critically evaluates MSC source variability, methodological limitations, and causes of clinical inconsistency. It aims to provide a conceptual framework to guide future mechanistic studies and clinical development of MSC-Treg-based therapies.</p>","PeriodicalId":21962,"journal":{"name":"Stem Cells International","volume":"2026 ","pages":"6457805"},"PeriodicalIF":3.6,"publicationDate":"2026-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13454365/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148707583","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":"Stem Cell Models for Elucidating Cellular Mechanisms of Substance Use Disorders and Advancing Addiction Pharmacology.","authors":"Ji Sun Koo, Huiping Zhang","doi":"10.1155/sci/1717710","DOIUrl":"10.1155/sci/1717710","url":null,"abstract":"<p><p>Substance use disorders (SUDs) impose major global morbidity and mortality, yet the cellular mechanisms linking genetic risk to neural vulnerability, disrupted neurodevelopment, and drug-induced neuroadaptations remain poorly understood. Human pluripotent stem cell (hPSC) technologies, including embryonic and induced pluripotent stem cell (ESC/iPSC)-derived neurons, three-dimensional (3D) brain organoids, and organoid-on-a-chip platforms, provide scalable, human-relevant models to address this gap. ESC/iPSC-derived neuronal cultures enable interrogation of genetic and epigenetic determinants of drug susceptibility and response; cerebral organoids recapitulate tissue architecture and emergent network dynamics; and microfluidic organoid-on-a-chip systems facilitate maturation, enhance reproducibility, and enable controlled exposure paradigms. In this review, we synthesize recent stem cell-based studies of alcohol, opioid, and stimulant exposure, highlighting insights into neurodevelopmental disruption, synaptic and signaling alterations, neuroinflammation, and network-level dysfunction. We critically evaluate limitations of stem cell-based studies, including ethical concerns, inter- and intra-line variability, incomplete cellular maturation, and difficulties in modeling complex circuitry and comorbid conditions. We propose strategies to enhance translational relevance, including standardized differentiation protocols, addition of patient-derived cells and vascular and immune components, and integration of multi-omics approaches (transcriptomics, epigenomics, and proteomics) with functional readouts to map molecular pathways underlying drug vulnerability and resilience. Finally, we outline the therapeutic and precision-medicine potential of stem cell platforms for target discovery, predictive toxicology, and individualized treatment modeling. Despite remaining challenges, stem cell-based approaches offer a powerful and increasingly tractable path from genetic association to mechanistic insight and therapeutic innovation in addiction research.</p>","PeriodicalId":21962,"journal":{"name":"Stem Cells International","volume":"2026 ","pages":"1717710"},"PeriodicalIF":3.6,"publicationDate":"2026-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13451643/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148697833","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":"FAP as a Clinical Biomarker: FAP+ CAFs Orchestrate an Immunosuppressive Stem Cell Niche via the COL1A1/2-CD44 Axis in Colon Cancer.","authors":"Qian Ding, Qingyan Lu","doi":"10.1155/sci/4678145","DOIUrl":"10.1155/sci/4678145","url":null,"abstract":"<p><strong>Background: </strong>Colon cancer (CC) remains a leading cause of cancer-related mortality worldwide, driven largely by the complex interactions within the tumor microenvironment (TME). Fibroblast activation protein (FAP) is highly expressed in cancer-associated fibroblasts (CAFs) and is associated with poor prognosis, yet its role in coordinating immune evasion and cancer stemness remains to be fully elucidated.</p><p><strong>Methods: </strong>We integrated multiomics data from TCGA and GEO databases, utilizing bulk RNA-seq and single-cell RNA-seq (scRNA-seq) analyses. Findings were validated via tissue microarray (TMA) immunohistochemistry (IHC). We further employed cell-cell communication analysis, pseudotime trajectory modeling, and the Connectivity Map (CMap) for drug sensitivity prediction and molecular docking.</p><p><strong>Results: </strong>FAP was significantly upregulated in CC tissues and correlated with advanced clinical stages. scRNA-seq confirmed that FAP is predominantly expressed in CAFs. Functional analysis revealed that FAP-high tumors are enriched in extracellular matrix (ECM) remodeling and immunosuppressive pathways. Cell-cell communication analysis identified that FAP+ CAFs interact with T cells and cancer stem cells (CSCs) primarily through the COL1A1/2-CD44 axis. Specifically, FAP+ CAFs promote the differentiation of naive T cells into regulatory T cells (Tregs) and are positively correlated with various stemness markers, including CD44, ABCG2, and BMI1. Based on these findings, we established a 14-gene prognostic risk model with robust predictive accuracy (area under the curve [AUC] > 0.64) and identified AS604850 and LY364947 as potential therapeutic agents.</p><p><strong>Conclusion: </strong>Our study demonstrates that FAP+ CAFs orchestrate a dual-functional \"immunosuppressive stem cell niche\" via the COL1A1/2-CD44 signaling axis. Targeting this FAP-driven niche provides a promising strategy for overcoming immunotherapy resistance and improving clinical outcomes in CC.</p>","PeriodicalId":21962,"journal":{"name":"Stem Cells International","volume":"2026 ","pages":"4678145"},"PeriodicalIF":3.6,"publicationDate":"2026-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13446019/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148685870","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":"The Effectiveness Based on Optimal Dose and Administration Route, and Safety Profiles of Stem Cells and Derived Products in the Treatment of Patients With Amyotrophic Lateral Sclerosis: A Systematic Review and Meta-Analysis.","authors":"Mahdieh Pourasghari, Soraya Babaie, Raha Markazi-Movaghar, Saba Salehpour, Bina Eftekharsadat, Azizeh Farshbaf-Khalili","doi":"10.1155/sci/4122493","DOIUrl":"10.1155/sci/4122493","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;This systematic review and meta-analysis aimed to evaluate the effectiveness of stem cell therapies for patients with amyotrophic lateral sclerosis (ALS) based on optimal dosing and administration routes, as well as the safety profiles of stem cells and their derived products.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;The review followed PRISMA guidelines and involved a comprehensive literature search up to October 2025, receiving ethical approval from Tabriz University of Medical Sciences and registration in PROSPERO. It utilized international databases, including PubMed/MEDLINE, Embase, Cochrane Library, Scopus, Web of Science, ProQuest, ClinicalTrials.gov, and Science Direct. The included studies comprised randomized controlled trials (RCTs), quasi-experimental studies, and other interventional designs involving ALS patients treated with stem cell therapies. In total, 31 studies were analyzed, featuring 7 controlled trials with 370 participants and 24 non-controlled pre-post studies with 460 participants. Heterogeneity was evaluated using &lt;i&gt;I&lt;/i&gt; &lt;sup&gt;2&lt;/sup&gt; statistics, and subgroup analyses were conducted based on treatment duration and dosing.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;A pooled analysis (treatment group: &lt;i&gt;n&lt;/i&gt; = 93; control group: &lt;i&gt;n&lt;/i&gt; = 90) demonstrated a significant attenuation in the progression of disease severity, as measured by the ALS Functional Rating Scale (ALSFRS), in stem cell groups versus controls (weighted mean difference [WMD]: 8.89 95% CI: 4.12-13.67; &lt;i&gt;p&lt;/i&gt; = 0.0003), which was beneficial for both the ≥10 × 10&lt;sup&gt;6&lt;/sup&gt; and &lt;10 × 10&lt;sup&gt;6&lt;/sup&gt; dose sub-groups. However, a meta-analysis of single-arm studies in two control (pre-intervention) and intervention phases (&lt;i&gt;n&lt;/i&gt; = 88) demonstrated no significant difference in progression of ALSFRS between study phases by time: month 3 (WMD: -1.27 (-3.01 to 0.47); &lt;i&gt;p&lt;/i&gt; = 0.15), month 6 (WMD: -2.69 (-5.62 to 0.25); &lt;i&gt;p&lt;/i&gt; = 0.07), month 9 (WMD: -1.55 (-3.49 to 0.39); &lt;i&gt;p&lt;/i&gt; = 0.12), and month 12 (WMD: -7.59 (-13.95 to -1.26); &lt;i&gt;p&lt;/i&gt; = 0.02). An accelerated decline in forced vital capacity (FVC) was observed during the intervention phase, with statistically significant reductions at month 3 (WMD: -10.91; 95% CI: -16.39 to -5.43; &lt;i&gt;p&lt;/i&gt; &lt; 0.0001) and month 6 (WMD: -15.97; 95% CI: -28.60 to -3.33; &lt;i&gt;p&lt;/i&gt; = 0.01) compared with the pre-intervention control phase. Nevertheless, sensitivity analyses excluding studies involving high-dose mesenchymal stem cell (MSC) therapies demonstrated that these differences were no longer statistically significant. Moreover, no significant change in progression rate was observed at month 9 (WMD: -8.10 (-18.25 to 2.06); &lt;i&gt;p&lt;/i&gt; = 0.12). The route of MSCs administration (intrathecal [IT], intramuscular [IM], and intravenous [IV]) had no effect on the results of ALSFRS and FVC, reinforced by sensitivity analyses. Adverse events were mostly mild, with headaches most frequent in high-dose groups.&lt;/p&gt;&lt;p&gt;","PeriodicalId":21962,"journal":{"name":"Stem Cells International","volume":"2026 ","pages":"4122493"},"PeriodicalIF":3.6,"publicationDate":"2026-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13439401/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148679742","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}