Stem Cells International最新文献

{"title":"Adipose-Derived Stem Cell Exosomes in Diabetic Wound Repair: Molecular Crosstalk, Bioengineering Strategies, and Translational Challenges.","authors":"Danna Yao, Yujie Xiao, Mali Zhou, Panpan Sun, Ling Wang, Hongtao Wang","doi":"10.1155/sci/4151678","DOIUrl":"10.1155/sci/4151678","url":null,"abstract":"<p><p>Diabetic wounds are sustained by persistent inflammation, impaired angiogenesis, abnormal extracellular matrix (ECM) remodeling, and delayed re-epithelialization. Adipose-derived stem cell exosomes (ADSC-Exos) offer a cell-free strategy because their multicomponent cargo can modulate immune responses, vascular regeneration, fibroblast activity, and epidermal repair. Mechanistic studies suggest that ADSC-Exos promote macrophage immunometabolic reprogramming, restore pro-angiogenic signaling, improve matrix homeostasis, and protect keratinocytes from oxidative injury. Engineering approaches and biomaterial-based delivery systems may further improve local retention, controlled release, and therapeutic activity. Distinct from existing ADSC-Exos reviews, this review adopts a pathology-to-translation framework that connects the major pathological features of diabetic wounds with ADSC-Exos mechanisms, engineering strategies, delivery optimization, and clinical translation. Particular emphasis is placed on donor- and process-dependent heterogeneity, potency assessment, GMP-compatible manufacturing, biodistribution, long-term safety, and regulation. Overall, ADSC-Exos represent a mechanistically compelling preclinical platform, but clinical translation will require reproducible product quality, standardized potency criteria, scalable manufacturing, and rigorous clinical validation.</p>","PeriodicalId":21962,"journal":{"name":"Stem Cells International","volume":"2026 ","pages":"4151678"},"PeriodicalIF":3.6,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13587927/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149008895","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":"Early-Onset Preeclampsia-Derived hUC-MSCs Exhibit Accelerated Initial Culture Kinetics Without Sustained Growth Advantage: A Comparative In Vitro Study.","authors":"İbrahim Alptekin, Bilge Alptekin, Ezel Erkan, Ferda Topal Celikkan, Derya Uyan Hendem, Dilek Şahin, Alp Can","doi":"10.1155/sci/3980640","DOIUrl":"10.1155/sci/3980640","url":null,"abstract":"<p><p>Preeclampsia (PE) is a pregnancy-related disorder associated with significant maternal and fetal morbidity, and intrauterine conditions may influence the biological behavior of human umbilical cord (UC)-derived mesenchymal stem cells (hUC-MSCs). However, comparative data between early-onset PE (EOPE) and late-onset PE (LOPE) remain limited. This study aimed to compare the in vitro growth kinetics of hUC-MSCs derived from pregnancies complicated by EOPE and LOPE. In this comparative in vitro study, UC samples (<i>n</i> = 66) were classified into three groups according to the maternal clinical condition: control (<i>n</i> = 22), EOPE (<i>n</i> = 22), and LOPE (<i>n</i> = 22). Cells were isolated using a mechanical explant method and cultured under standard conditions. Culture parameters, including cell-outgrowth time, time to 90% confluency (<i>P</i> ₀), first passage duration (<i>P</i> ₁), and total culture duration (<i>P</i> ₀+<i>P</i> ₁), were recorded. Population doubling time (PDT) was calculated using both outgrowth-adjusted and <i>P</i> ₁-based approaches, and phenotypic characterization was performed by flow cytometry. Cell-outgrowth time did not differ significantly among the groups (<i>p</i> = 0.930). <i>P</i> ₀ duration differed significantly among the groups (<i>p</i> < 0.001). EOPE-derived cells exhibited a shorter <i>P</i> ₀ duration (19.00 ± 2.19 days) than both control-derived cells (21.65 ± 1.63 days; Tukey-adjusted <i>p</i> = 0.0004) and LOPE-derived cells (20.71 ± 2.35 days; Tukey-adjusted <i>p</i> = 0.0266). <i>P</i> ₁ duration and total culture duration did not differ significantly among the groups (<i>p</i> = 1.000 and <i>p</i> = 0.090, respectively). The outgrowth-adjusted group-level PDT estimate was lower in EOPE (16.6 h) than in LOPE (18.4 h) and controls (19.1 h), whereas the <i>P</i> ₁-based PDT estimates were closely similar across the groups (~32 h). Total cell yield and viability were numerically similar across the groups. These findings indicate that EOPE-derived hUC-MSCs exhibit an early culture-specific kinetic difference, predominantly reflected by a shorter <i>P</i> ₀ duration, without a sustained difference in subsequent <i>P</i> ₁ expansion or total culture duration. The accelerated early growth may reflect adaptive responses to the intrauterine environment rather than enhanced functional potential, suggesting that early culture parameters may serve as sensitive indicators of disease-related alterations.</p>","PeriodicalId":21962,"journal":{"name":"Stem Cells International","volume":"2026 ","pages":"3980640"},"PeriodicalIF":3.6,"publicationDate":"2026-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13570448/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148956473","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":"Mechanisms of Mesenchymal Stem Cell-Derived Exosomes in Dry Eye Disease: From Inflammation Pathways to Therapeutic Prospects.","authors":"Jiahuan Yi, Fangfang Lu, Yale Tian, Yu Wang, Zihe Zhang, Xujie Deng, Zhi Wang, Shigang Xia, Jia Zhang, Qiguo Xiao","doi":"10.1155/sci/2026673","DOIUrl":"10.1155/sci/2026673","url":null,"abstract":"<p><p>Dry eye disease (DED) is a chronic ocular surface disorder triggered by tear film imbalance, in which inflammatory disruption of immune homeostasis constitutes the core pathological mechanism. Mesenchymal stem cell-derived exosomes (MSC-Exos) offer promising anti-inflammatory therapeutic potential through immune modulation, tissue repair, and their inherently low immunogenicity. This review elucidates MSC-Exos' molecular regulation of DED inflammation, demonstrating their suppression of the TLR4/NF-κB signaling axis, the IRAK1/TRAF6/NF-κB cascade reaction, the STAT3 transcriptional regulatory network, and the NLRP3 inflammasome activation pathway, while revealing a synergistic mechanism through which MSC-Exos ameliorate the ocular surface inflammatory microenvironment by modulating the Th17/Treg immune balance via the gut-eye axis and facilitating FBXW7-mediated ubiquitination degradation pathways. Despite this therapeutic potential, clinical translation is hampered by exosomal heterogeneity, difficulties in standardization, and suboptimal delivery efficiency and long-term efficacy. Future progress will require the integration of nanotechnology and gene editing to enhance therapeutic functionality, ultimately positioning MSC-Exos as precision biologics for DED.</p>","PeriodicalId":21962,"journal":{"name":"Stem Cells International","volume":"2026 ","pages":"2026673"},"PeriodicalIF":3.6,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13555284/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148921113","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":"Correction to \"Adipose-Derived Stem Cell Exosomes Antagonize the Inhibitory Effect of Dihydrotestosterone on Hair Follicle Growth by Activating Wnt/<i>β</i>-Catenin Pathway\".","authors":"","doi":"10.1155/sci/9789426","DOIUrl":"https://doi.org/10.1155/sci/9789426","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1155/2023/5548112.].</p>","PeriodicalId":21962,"journal":{"name":"Stem Cells International","volume":"2026 ","pages":"9789426"},"PeriodicalIF":3.6,"publicationDate":"2026-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13548133/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148906930","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":"Biological Characteristics of Stromal Cells Differ Between Primary Lung Adenocarcinoma, Peritumoral Lung, and Distal Lung Tissues.","authors":"Go Kamimura, Masaya Aoki, Tao-Sheng Li, Tatsuhiko Furukawa, Masatatsu Yamamoto, Yuka Ishihara, Kohichi Kawahara, Kazuhiro Ueda","doi":"10.1155/sci/6807362","DOIUrl":"10.1155/sci/6807362","url":null,"abstract":"<p><strong>Background: </strong>Stromal cells are known to play critical roles in the development and progression of solid tumors including lung cancers. This study was proposed to clarify the biological features of stromal cells from intratumoral, peritumoral lung, and distal lung tissues of primary lung adenocarcinoma patients.</p><p><strong>Methods: </strong>Surgically resected lung lobes containing primary adenocarcinoma were used for isolating stromal cells. Tumor tissue, peritumoral lung tissue, and distal lung tissue were sampled and cut into small pieces for culture as \"explants.\" The biological features of stromal cells were evaluated by cell isolating efficiency, cell morphology, cell surface marker, gene expression profile, and cytokine secretion.</p><p><strong>Results: </strong>Spindle shaped fibroblast-like cells were outgrown successfully from the \"explants\" with comparable efficiency among different tissues. All outgrowth cells were vimentin-positive and cytokeratin-negative, consistent with stromal cell phenotypes. Quantitative analysis on the width-to-length ratio of cells indicated different morphological differences among stromal cells. Moreover, the expression of α-smooth muscle actin (α-SMA), a marker for cancer-associated fibroblasts (CAFs), was more extensively observed in stromal cells from tumor tissues than others and, its PCR array showed higher expression of extracellular matrix (ECM)-related factors <i>COL11A1</i> and <i>TIMP3</i>, in contrast, cytokine array analysis revealed more abundant release of immune-suppressive factors from stromal cells of peritumoral tissues.</p><p><strong>Conclusion: </strong>Stromal cells from tumor, peritumoral, and distal lung tissues display distinct biological characteristics. Further investigation is needed to elucidate their specific roles in tumor progression.</p>","PeriodicalId":21962,"journal":{"name":"Stem Cells International","volume":"2026 ","pages":"6807362"},"PeriodicalIF":3.6,"publicationDate":"2026-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13550995/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148913685","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":"Evidence for a Neural Stem Cell Niche in the Postnatal Rat Vestibular Ganglion: An In Vitro Study.","authors":"Sabine Sommerer, Kristen Rak, Bjoern Spahn, Stephan Hackenberg, Johannes Voelker, Jonas Engert","doi":"10.1155/sci/5567583","DOIUrl":"10.1155/sci/5567583","url":null,"abstract":"<p><p>Vestibular dysfunction significantly contributes to dizziness, balance issues, and falls, yet causal treatments are still unavailable. The vestibular ganglion (VG), the primary sensory ganglion of the vestibular nerve, is increasingly seen as a key site of vestibular degeneration. Neural stem cells (NSCs) have been identified in several areas of the auditory and vestibular pathways. Endogenous activation of NSCs represents a promising regenerative strategy. However, the presence of NSCs within the VG remains uncertain. In this study, VG tissue from postnatal day (PND) 8 Sprague-Dawley rats was isolated, enzymatically dissociated, and cultured in serum-free neurosphere conditions. The dissociated VG cells reliably formed free-floating neurospheres that grew over multiple passages. Immunocytochemistry showed expression of NSC and progenitor markers, including Sox-2, Nestin, Musashi-1, Atoh-1, and doublecortin, in both neurospheres and VG tissue sections. Additional analyses demonstrated persistence of Sox-2-, Atoh-1-, and Nestin-positive populations in the adult VG. After differentiation, individual cells from neurospheres developed into β-III-tubulin-positive neurons, glial fibrillary acidic protein (GFAP)-positive astrocytes, and myelin basic protein (MBP)-positive myelinating glial cells, while a significant portion retained Nestin expression, indicating a progenitor-like state. These findings demonstrate that VG-derived cells meet the main criteria of NSCs: self-renewal, progenitor formation, and multipotent differentiation into neuronal and glial lineages. Our results provide the first evidence of a neurogenically capable cell population in the postnatal rat VG and support the persistence of progenitor-associated cell populations into adulthood. This identifies the VG as a novel endogenous regenerative reservoir, positioning it as a promising target for strategies that activate resident cells to restore vestibular function.</p>","PeriodicalId":21962,"journal":{"name":"Stem Cells International","volume":"2026 ","pages":"5567583"},"PeriodicalIF":3.6,"publicationDate":"2026-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13547954/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148906996","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":"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":"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":"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}