Stem Cells International最新文献

{"title":"Fibrinogen Alpha Chain (FGA) Associates With Epithelial-Mesenchymal Transition, Stemness, and the USP-Catenin Complex in Colorectal Cancer.","authors":"Hao Lin, Weixu Chen, Qing Li","doi":"10.1155/sci/9599574","DOIUrl":"https://doi.org/10.1155/sci/9599574","url":null,"abstract":"<p><strong>Background: </strong>Colorectal cancer (CRC) progression is heavily driven by epithelial-mesenchymal transition (EMT) and the acquisition of cancer stem cell (CSC) properties. Elucidating the specific molecular drivers and dynamic indicators underlying these processes is crucial for advancing CRC management.</p><p><strong>Methods: </strong>The clinical significance and diagnostic value of fibrinogen alpha chain (FGA) were evaluated using TCGA data, immunohistochemistry (IHC), and paired pre- and postoperative serum samples. The biological functions of FGA were assessed in HCT116 cells through Transwell and 3D spheroid formation assays. Immunoprecipitation-mass spectrometry (IP-MS) and protein-protein interaction (PPI) network analyses were utilized to uncover the underlying molecular mechanisms.</p><p><strong>Results: </strong>FGA mRNA and protein are significantly upregulated in CRC tissues, and preliminary data indicate elevated serum FGA in CRC patients. Clinically, aberrant FGA expression correlates with tumor histological type, lymphatic invasion, and poor survival outcomes. In vitro, FGA overexpression is associated with the downregulation of E-cadherin, upregulation of mesenchymal markers (Vimentin, ZEB1, Snail), and increased cell migration and spheroid formation. Mechanistically, IP-MS identified a potential PPI network wherein FGA associates with ubiquitin-specific proteases (USP7, USP10) and the catenin complex (β-catenin, p120-catenin), suggesting a potential role in mediating pro-stemness signaling.</p><p><strong>Conclusion: </strong>These findings suggest that FGA may contribute to CRC plasticity by modulating EMT and stem-like properties in vitro. Furthermore, its dynamic postoperative reduction warrants further investigation to determine its utility for non-invasive tumor monitoring.</p>","PeriodicalId":21962,"journal":{"name":"Stem Cells International","volume":"2026 ","pages":"9599574"},"PeriodicalIF":3.6,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13678855/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149224601","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":"Strategies for Differentiation of Corneal Endothelial Cells From Stem Cells: Current Advances and Challenges.","authors":"Ling Li, Yan Huang, Yuanyuan Wu, Qiuping Wang, Jing Ji, Lizhen Wang","doi":"10.1155/sci/5329168","DOIUrl":"https://doi.org/10.1155/sci/5329168","url":null,"abstract":"<p><p>The corneal endothelium, located in the posterior layer of the cornea, is critical to the maintenance of corneal clarity. Due to the limited proliferative capacity of the corneal endothelium, cell loss or damage can affect visual health. The lack of healthy corneal donors worldwide limits corneal transplantation, which is still the most successful clinical treatment. Since stem cells possess self-renewal capacity and can differentiate into various cell types including corneal endothelial cells (CECs), they represent a promising candidate for regenerative medicine. Many methods have been developed to induce stem cells to differentiate into CECs, mainly including chemical induction, physical induction, and coculture with adult corneal cells such as lens epithelial cells and CECs. In this review, the structure, function and marker identification of CECs are firstly introduced. Then, the methods and research progress regarding the differentiation of multipotent stem cells (mesenchymal stem cells [MSCs]) and pluripotent stem cells (embryonic stem cells [ESCs] and induced pluripotent stem cells [iPSCs]) into CECs are reviewed in detail, and both in vivo and clinical applications of stem cell-derived CECs are discussed. Finally, the challenges in stem cell differentiation into CECs are summarized, and future development directions are suggested.</p>","PeriodicalId":21962,"journal":{"name":"Stem Cells International","volume":"2026 ","pages":"5329168"},"PeriodicalIF":3.6,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13650382/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149167988","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":"Beyond the Cell: Stem Cell-Derived Exosomes as Next-Generation Tools in Regenerative Therapy.","authors":"Hazem A El-Kady, Majdeldin E Abdelgilil, Hagar W Mandour, Rahaf Altartoor, Ziad Mustafa Abd El-Wahab, Sarah Alosman, Soha M Abdelzaher, Ibrahim M Fangary, Yasmine Hosny","doi":"10.1155/sci/1054968","DOIUrl":"10.1155/sci/1054968","url":null,"abstract":"<p><p>Exosomes derived from stem cells have gained significant interest in recent years due to their considerable promise as a cell-free therapy in drug delivery and regenerative medicine. Their therapeutic appeal lies in their immune-modulating properties, along with a lower risk of immune response or tumor formation compared to whole cell-based therapies. It has been highlighted that exosomes can be engineered to deliver therapeutic molecules such as RNAs, proteins, and drugs to specific cells, tissues, and organs, making them a promising tool for targeted therapies. This review summarizes the sources of exosomes from different types of stem cells, covering the components of their molecular cargos from different types of RNAs, proteins, growth factors, and other molecules. The focus is on the different advanced methods used to isolate and characterize the exosomes. Exosomes have many therapeutic applications related to cancer, cardiovascular diseases, neurodegenerative disease, wound healing, bone repair, and renal and hepatic injuries.</p>","PeriodicalId":21962,"journal":{"name":"Stem Cells International","volume":"2026 ","pages":"1054968"},"PeriodicalIF":3.6,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13643360/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149128361","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":"Renovascular Disease and Its Impact on Endogenous Kidney Repair: Stem/Progenitor Cells.","authors":"Vinaya C Iyer, Lilach O Lerman, Alfonso Eirin","doi":"10.1155/sci/4007512","DOIUrl":"https://doi.org/10.1155/sci/4007512","url":null,"abstract":"<p><strong>Background: </strong>Renovascular disease (RVD), a progressive condition characterized by narrowing or occlusion of the renal arteries, is an important cause of secondary hypertension and chronic kidney disease (CKD) in older adults, associated with high cardiovascular morbidity and mortality. Recent evidence suggests that RVD compromises renal repair by impairing complementary vascular, stromal, and tubular repair systems, including endothelial progenitor cells (EPCs), mesenchymal stem/stromal cells (MSCs), and tubular regenerative pathways.</p><p><strong>Summary: </strong>RVD exposes these endogenous repair cells to multiple injurious stressors, including renal ischemia, hypertension, mechanical stretch, renin-angiotensin-aldosterone system (RASS) activation, and hypoxia. These upstream stressors trigger convergent cellular mechanisms, including oxidative stress, mitochondrial dysfunction, epigenetic and post-transcriptional (mRNA/miRNA) alterations, endoplasmic reticulum (ER) stress, cellular senescence, and apoptosis, leading to impaired reparative capacity. Cardiovascular comorbidities, including obesity, diabetes, and metabolic syndrome (MetS), further exacerbate these maladaptive responses. Experimental studies suggest that mitoprotective agents, epigenetic and miRNA modulators, ER-stress inhibitors, and extracellular vesicle (EV)-based therapies may preserve or restore stem/progenitor cell function.</p><p><strong>Key messages: </strong>This review summarizes the current understanding of the impact of RVD on endogenous renal repair, focusing on the complementary roles of EPCs, MSCs, and tubular regenerative pathways, including resident renal progenitor cells, scattered tubular-like cells (STCs), and injury-induced epithelial plasticity. We discuss how common pathological stressors converge on shared molecular pathways to impair endogenous repair and highlight emerging therapeutic strategies aimed at preserving or restoring the regenerative capacity of these endogenous repair systems.</p>","PeriodicalId":21962,"journal":{"name":"Stem Cells International","volume":"2026 ","pages":"4007512"},"PeriodicalIF":3.6,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13625202/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149114840","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":"CD73-Overexpressing ADSCs Promote Neurogenic Bladder Repair via A2A-JAK1/STAT3-Mediated Modulation of Inflammation and Macrophage Polarization.","authors":"Guanqun Zhu, Guoyi Jiang, Jiao Huang, Yuxuan He, Zongliang Zhang, Rui Zhang, Xinbao Yin, Kai Zhao, Xiaokun Yang, Woong Jin Bae, Ke Wang","doi":"10.1155/sci/8564160","DOIUrl":"https://doi.org/10.1155/sci/8564160","url":null,"abstract":"<p><strong>Background: </strong>Neurogenic bladder (NB) is characterized by chronic inflammation and bladder tissue injury, and current treatments fail to restore the inflammatory microenvironment or tissue integrity. Although adipose-derived stem cell (ADSC) therapy shows regenerative potential, its efficacy is limited by inflammation; whether CD73 overexpression enhances ADSC therapeutic effects in NB remains unclear.</p><p><strong>Methods: </strong>A rat model of NB was established via pelvic nerve (PN) injury and treated with CD73-overexpressing ADSCs (CD73⁺ADSCs). Bladder function, histological remodeling, and apoptosis were evaluated in vivo. In vitro, conditioned medium (CM) from CD73⁺ADSCs was applied to LPS-injured rat bladder transitional epithelial cells (RB-TECs) and macrophages to assess proliferation, migration, apoptosis, inflammatory responses, and macrophage polarization. Key signaling pathways were examined, and label-free quantitative (LFQ) proteomics was performed to characterize global molecular reprogramming.</p><p><strong>Results: </strong>CD73⁺ADSCs significantly improved urodynamic function, restored smooth muscle architecture, and reduced apoptosis in NB rats. In vitro, CD73⁺ADSC-CM promoted urothelial cell proliferation and migration while attenuating cell death. Mechanistically, CD73⁺ADSCs enhanced extracellular adenosine production, at least partly dependent on pharmacologically sensitive A2A receptor signaling, suppressed NF-κB activation, reduced proinflammatory cytokine release, promoted macrophage polarization toward an M2 phenotype, and inhibited NLRP3 inflammasome activation. Proteomic analysis revealed a global shift toward antiinflammatory and reparative molecular programs.</p><p><strong>Conclusion: </strong>Our findings suggest that CD73 contributes to the immunomodulatory and reparative properties of ADSCs under inflammatory conditions. By coordinating adenosinergic signaling, inflammatory suppression, and repair-associated pathways, CD73⁺ADSCs effectively reprogram the NB microenvironment and represent a promising regenerative therapeutic strategy for NB.</p>","PeriodicalId":21962,"journal":{"name":"Stem Cells International","volume":"2026 ","pages":"8564160"},"PeriodicalIF":3.6,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13624695/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149114804","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 Role and Mechanism of Hair Follicle Neural Crest Stem Cells and Their Small Extracellular Vesicles in Repair of Peripheral Nerve Injury.","authors":"Jiachen Zheng, Siying Fei, Yang Xu, Chi Zhang, Haiyan Lin, Fang Liu","doi":"10.1155/sci/1665875","DOIUrl":"10.1155/sci/1665875","url":null,"abstract":"<p><p>Peripheral nerve injury (PNI) remains a vital clinical challenge due to the limited efficacy of current therapeutic strategies. Autologous nerve grafting, the gold standard for repairing PNI, remains limited by certain donor site morbidity, and alternative approaches include cell therapy, nerve conduits, gene therapy, and electrical stimulation with immune rejection and ethical controversies. Yet, hair follicle neural crest stem cells (hfNCSCs), a pluripotent cell population originating from the embryonic neural crest, have emerged as a promising candidate. hfNCSCs exhibit high differentiation potential, ethical acceptability, and accessibility, possessing significant advantages in axonal regeneration and functional recovery. Concurrently, small extracellular vesicles (sEVs) derived from stem cells have garnered increasing attention for their low immunogenicity, non-tumorigenicity, and convenient storage. Preclinical studies highlight their synergistic potential in modulating neuroinflammation, enhancing Schwann cell (SC) activity, and promoting nerve repair. This review summarizes recent advances in hfNCSCs and sEVs for PNI repair, with a focus on molecular mechanisms and translational applications. We further discuss the challenges and future directions of hfNCSCs-sEVs as a cell-free therapeutic strategy in neural regeneration.</p>","PeriodicalId":21962,"journal":{"name":"Stem Cells International","volume":"2026 ","pages":"1665875"},"PeriodicalIF":3.6,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13621818/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149081243","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":"Human Umbilical Cord Mesenchymal Stem Cell-Derived Exosomes Attenuate IMQ-Induced Psoriasiform Dermatitis: A Preclinical Experimental Study of Exosomal miR-125b-5p/STAT3 Signaling.","authors":"Ziyan Li, Rui Ren, Yunjia Wang, Zhichao Fan, Yijun Zhang, Jieling Fu, Jiaxin Huang, Yuting Huang, Kaiyuan Zhang, Qian Li","doi":"10.1155/sci/4935728","DOIUrl":"10.1155/sci/4935728","url":null,"abstract":"<p><strong>Background and aims: </strong>Psoriasis is a chronic inflammatory skin disease driven largely by dysregulation of the IL-23/Th17 axis and excessive keratinocyte proliferation. Human umbilical cord mesenchymal stem cell (MSC)-derived exosomes (hucMSC-Exos) represent a potential cell-free therapeutic strategy, but their mechanisms remain incompletely defined. This study evaluated the effects of hucMSC-Exos in psoriasiform inflammation and investigated the contribution of exosomal miR-125b-5p and its relationship with STAT3 signaling.</p><p><strong>Methods: </strong>hucMSC-Exos were isolated by differential ultracentrifugation and characterized by nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM), and immunoblotting. Therapeutic effects were assessed in an imiquimod (IMQ)-induced mouse model of psoriasiform dermatitis using PASI-like scoring, histopathology, immunohistochemistry, flow cytometry, and western blotting. Exosomal microRNAs (miRNAs) were profiled by high-throughput sequencing. STAT3 targeting was examined by dual-luciferase reporter assays, and the functional contribution of miR-125b-5p was assessed using exosomes loaded with a miR-125b-5p inhibitory oligonucleotide and negative-control exosomes (NC-Exos).</p><p><strong>Results: </strong>hucMSC-Exos alleviated IMQ-induced psoriasiform dermatitis, as reflected by reduced epidermal hyperplasia and fewer Ki-67-positive keratinocytes. Exosome treatment was associated with decreased phosphorylation of STAT3 and JNK, lower IL-23 and IL-17A expression, decreased Th17-cell frequency, and increased regulatory T cell (Treg)-cell frequency. In vitro, hucMSC-Exos suppressed Th17-cell proliferation while promoting Treg-cell expansion. miR-125b-5p was among the abundant miRNAs detected in hucMSC-Exos, and dual-luciferase reporter assays supported STAT3 as a direct target of miR-125b-5p. Compared with NC-Exos, inhibitor-loaded exosomes (IN-Exos) were less effective at alleviating IMQ-induced psoriasiform dermatitis; this reduced efficacy was accompanied by increased STAT3 and JNK phosphorylation, higher IL-23 and IL-17A expression, a higher Th17-cell frequency, and a lower Treg-cell frequency.</p><p><strong>Conclusion: </strong>hucMSC-Exos attenuated psoriasiform inflammation and were associated with reduced inflammatory signaling, decreased Th17-cell frequency, and increased Treg-cell frequency. Our findings further suggest that exosomal miR-125b-5p contributes, at least in part, to these effects through direct regulation of STAT3.</p>","PeriodicalId":21962,"journal":{"name":"Stem Cells International","volume":"2026 ","pages":"4935728"},"PeriodicalIF":3.6,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13613942/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149064445","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":"Efficacy of Fetal MSC Therapy for Osteogenesis Imperfecta: A Systematic Review and Meta-Analysis in Mice.","authors":"Rakila Kurugalage, Aditya Mukherjee, Arian Bhatia, Ruurd L Jaarsma, Krasimir Vasilev, Richard Bright, Vi-Khanh Truong","doi":"10.1155/sci/7815746","DOIUrl":"10.1155/sci/7815746","url":null,"abstract":"<p><strong>Background: </strong>Osteogenesis imperfecta (OI) is a genetic disorder marked by collagen defects that cause skeletal fragility. Current treatments improve bone density but not bone quality or fracture rates. Fetal mesenchymal stem cells (fMSCs) show superior osteogenic and immunomodulatory potential compared with adult mesenchymal stem cells (MSCs) and may offer a disease-modifying therapy.</p><p><strong>Methods: </strong>Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines, we systematically reviewed preclinical murine studies assessing the use of fMSC transplantation for OI. Data from eligible studies were pooled using random-effects meta-analysis (Hartung-Knapp adjustment). Risk ratios (RRs) were used for fracture incidence and standardized mean differences (SMDs) for mechanical and structural outcomes.</p><p><strong>Results: </strong>Four studies (219 mice: 91 treated, 128 controls) met inclusion criteria. fMSC treatment significantly reduced total long-bone fracture incidence (RR = 0.30; 95% confidence interval [CI]: 0.13-0.72; <i>p</i> = 0.027). Nonsignificant trends favored fMSC therapy for maximum load (SMD = 0.60), bone volume fraction (SMD = 0.40), cortical thickness (SMD = 0.65), and stiffness (SMD = 0.57). Heterogeneity among secondary outcomes reflected methodological variability and differences in engraftment efficiency.</p><p><strong>Conclusions: </strong>fMSC transplantation significantly reduces fracture burden and shows consistent trends toward improved bone structure and strength in OI murine models. These findings support the need for further standardized, multicenter studies to optimize cell delivery, enhance engraftment, and validate clinical efficacy in humans. However, given the small evidence base, lack of independent replication, and reliance on a single OI mouse model, these findings should be interpreted as exploratory and hypothesis-generating rather than confirmatory.</p>","PeriodicalId":21962,"journal":{"name":"Stem Cells International","volume":"2026 ","pages":"7815746"},"PeriodicalIF":3.6,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13614066/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149064365","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 Use of Human Platelet Lysate (hPL) Enables 3D Cultivation of ADSCs Derived From Human Breast Tissue.","authors":"Annelie Koenen, Annemarie Schroeder, Toralf Reimer, Guido Hildebrandt, Katrin Manda","doi":"10.1155/sci/3165313","DOIUrl":"https://doi.org/10.1155/sci/3165313","url":null,"abstract":"<p><strong>Background: </strong>For the application of mesenchymal stem cells (MSCs) in regenerative medicine, xeno-free ex vivo cultivation is necessary. Therefore, this study aimed to investigate whether adipose-derived stem cells (ADSCs) from human breast tissue could be cultivated with human platelet lysate (hPL)-a promising alternative derived from human platelets-instead of fetal bovine serum (FBS).</p><p><strong>Methods: </strong>The influence of hPL within the culture medium of ADSCs from the female breast was analyzed regarding immunophenotype, adipogenic differentiation capacity, growth kinetics, and cell cycle distribution of ADSCs. Subsequently, the formation of spheres in hPL-supplemented medium was characterized in detail.</p><p><strong>Results: </strong>In comparison to FBS, the supplementation of medium with hPL resulted in a change in morphology, but the immunophenotype remained unchanged. Furthermore, supplementation of the medium with hPL caused an improved adipogenic differentiation capacity, increased growth, and shortened population doubling time (PDT) in ADSCs. Additionally, the cultivation of ADSCs with hPL led to spontaneous formation of spheres.</p><p><strong>Conclusion: </strong>hPL is not only a replacement for the ethically controversial cell culture additive FBS but also offers a xeno-free method for the cultivation of breast tissue-derived ADSCs and thus represents an important step from bench to bedside.</p>","PeriodicalId":21962,"journal":{"name":"Stem Cells International","volume":"2026 ","pages":"3165313"},"PeriodicalIF":3.6,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13598434/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149040637","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":"PDGFRβ in Stem Cell Microenvironments: Cross-Tissue Evidence and Hypotheses for the Limbal Stem Cell Niche.","authors":"Shuying Liao, Guigang Li","doi":"10.1155/sci/1536168","DOIUrl":"https://doi.org/10.1155/sci/1536168","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Stem cells reside within specialized microenvironments, termed niches, composed of vascular networks, stromal cells, extracellular matrix (ECM), immune components, and neural elements, which collectively regulate quiescence, self-renewal, and lineage commitment of stem cells. Platelet-derived growth factor receptor-β (PDGFRβ), a class III receptor tyrosine kinase (RTK) predominantly expressed in perivascular and mesenchymal stromal cells, has been associated with vascular-stromal organization across multiple stem cell systems. Rather than acting mainly as a direct determinant of stemness-associated transcriptional programs, PDGFRβ may influence stem cell behavior indirectly by modulating vascular stability, matrix remodeling, metabolic gradients, and biomechanical signaling. Evidence from hematopoietic stem cells (HSCs), mesenchymal stem cells (MSCs), neural stem cells (NSCs), tumor stem cells (TSCs), renal glomerular cells, and limbal stem cells (LSCs) indicates that PDGFRβ&lt;sup&gt;+&lt;/sup&gt; stromal or perivascular cells contribute to niche architecture and function in a context-dependent manner. Through interactions with platelet-derived growth factor-B (PDGF-B), vascular endothelial growth factor (VEGF), hypoxia-related signaling, inflammatory mediators, and integrin-dependent mechanotransduction, PDGFRβ is linked to angiogenesis, stromal cell activation, ECM remodeling, and niche biomechanics. Under physiological conditions, such regulation may support tissue maintenance, repair, and regeneration, whereas persistent or dysregulated activation may contribute to fibrosis, vascular dysfunction, tumor progression, and disruption of stem cell equilibrium. This review summarizes the current understanding of PDGFRβ as a vascular-stromal component associated with stem cell niche regulation, with emphasis on cross-tissue mechanisms and context-dependent differences. Particular attention is given to the LSC niche, where PDGFRβ&lt;sup&gt;+&lt;/sup&gt; limbal niche cells (LNCs) are discussed in relation to the Palisades of Vogt, limbal vessels, basement membrane/ECM organization, and epithelial progenitor maintenance. We distinguish established evidence for PDGFRβ expression and LNC-associated stromal identity from proposed mechanisms involving vascular-stromal support, ECM remodeling, biomechanical regulation, and LSC repair. Because receptor-specific functional evidence for PDGFRβ in limbal microenvironmental cells remains limited, the limbal component of this review is presented as a hypothesis-generating framework rather than as established evidence that PDGFRβ functionally regulates the limbal niche. Collectively, available evidence supports PDGFRβ as a candidate link between vascular-stromal organization and stem cell functional states, while underscoring the need for direct PDGFRβ perturbation studies in LNCs to define its functional relevance in limbal niche stability and corneal epithelial regeneration. This framework may guide future studies of PDGFRβ-asso","PeriodicalId":21962,"journal":{"name":"Stem Cells International","volume":"2026 ","pages":"1536168"},"PeriodicalIF":3.6,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13598441/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149040543","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}