Stem Cells Translational Medicine最新文献

{"title":"Extracellular vesicles conjugated with c(RGDyk) peptide targeting integrin αVβ3 repair optic nerve injury through YAP/TAZ and Smad2/3 signaling.","authors":"Mira Park, Hyun Ah Shin, Hey Jin Lee, Jong Hyun Moon, Jun Yong Kim, Won-Kyu Rhim, Dong Keun Han, Helen Lew","doi":"10.1093/stcltm/szag006","DOIUrl":"10.1093/stcltm/szag006","url":null,"abstract":"<p><p>Extracellular vesicles (EVs) derived from mesenchymal stem cells have therapeutic potential for optic nerve injury. However, further investigations are needed to increase their efficacy. In this study, we tried to enhance targeting and recovery function of EVs using conjugation with integrin αVβ3 antagonist-c(RGDyk) peptide. The molecular mechanism of neuronal repair was investigated as a potential treatment for optic nerve injury. EVs were shown to restore effectively the abnormal regulations of neuronal markers in optic nerve injury models. Notably, the functionally optimized c(RGDyK)_EVs exhibited superior targeting capabilities and modulated neuroregeneration in cases of hypoxic damage and inflammation. Single-cell RNA-seq analysis of R28 cells revealed significant regulation of transcription of genes involved in retinal ganglion cell (RGC) regeneration, neuronal growth, and inflammation by c(RGDyK)_EVs via the Yap-Taz signaling pathway. This study highlighted the enhanced therapeutic potential of c(RGDyK)_EVs over naïve EVs in the context of optic nerve disease. The findings suggested that c(RGDyK)_EVs hold promise as an alternative therapy for optic nerve injury.</p>","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":"15 3","pages":""},"PeriodicalIF":5.9,"publicationDate":"2026-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12948935/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147318220","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alveolar ridge preservation with lyophilized microspheres of human dental pulp stem cells following 3D dynamic osteogenic induction.","authors":"Yangyang Li, Jethro Zih-Shuo Wang, Zihan Yang, Fawen Wang, Haoyu Li, Chi Yang, Wenwen Yu, Zhiyuan Zhang","doi":"10.1093/stcltm/szag015","DOIUrl":"10.1093/stcltm/szag015","url":null,"abstract":"<p><p>The clinical use of bone graft materials for alveolar ridge preservation following tooth extraction has become a standard procedure to facilitate subsequent implant restoration and prosthetic rehabilitation. However, the therapeutic efficacy of these materials is substantially limited by their bio-inertness, lack of cellular activity, and unpredictable resorption rates. The development of bioactive osteogenic materials capable of host integration and active promotion of bone regeneration would represent a significant advancement over current clinical protocols. To address this challenge, our research has focused on developing bioactive biomaterials using human dental pulp stem cells (hDPSCs). This study proposes a novel strategy for alveolar ridge repair utilizing lyophilized hDPSC microspheres preconditioned through a three-dimensional (3D) dynamic osteogenic induction system. We cultured hDPSCs into 3D microspheres and subjected them to osteogenic induction within our established dynamic culture system, followed by lyophilization to prepare \"off-the-shelf\" osteogenic tissues. The resulting lyophilized microsphere constructs were implanted into fresh extraction sockets of SD rats and New Zealand white rabbits and evaluated over 4 weeks. Comparative analysis demonstrated that the lyophilized microsphere group exhibited significantly enhanced alveolar bone preservation, superior new bone formation, and improved bone microarchitecture compared to both control groups and traditional artificial bone powder groups. This preclinical study validates the potential of lyophilized hDPSC microspheres as an efficient and clinically promising bioactive material for post-extraction alveolar ridge reconstruction.</p>","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":"15 3","pages":""},"PeriodicalIF":5.9,"publicationDate":"2026-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12989099/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147463825","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The global regulatory landscape of stem cell medical aesthetics: challenges, comparisons, and pathways to coordination.","authors":"Yiding Xiao, Zirui Liao, Hailin Zhang, Tianjia Guan","doi":"10.1093/stcltm/szaf079","DOIUrl":"10.1093/stcltm/szaf079","url":null,"abstract":"<p><p>This paper systematically examines the regulatory frameworks of major regulatory bodies-including the United States, the European Union, Japan, South Korea, and China-regarding the use of stem cells and their derivatives (such as conditioned media and exosomes) for cosmetic purposes. Despite the rapid global growth of \"stem cell medical aesthetics\" within the cosmetic medical market, its scientific evidence remains insufficient, and it faces the core challenge of inconsistent regulatory systems. Through in-depth comparative analysis, this paper not only reveals profound differences among nations in risk perception, regulatory philosophy, and terminology definitions, but also dissects the resulting market fragmentation and patient safety risks. Based on this, the paper proposes feasible pathways to advance international regulatory coordination: The primary task is to unify core definitions and classification standards (especially for derivatives like exosomes) based on scientific consensus, and establish a risk-based tiered regulatory mechanism that clearly distinguishes medical from cosmetic applications. Concurrently, fundamental research should be strengthened and specific efficacy assessment standards (e.g., instrument measurements and patient-reported outcomes) should be developed. Crucially, this paper advocates for a hybrid regulatory model integrating conditional approval with real-world evidence tracking as a pragmatic solution balancing patient safety and technological innovation. This research aims to provide theoretical support and practical guidance for constructing a global governance framework that safeguards safety while accommodating innovation efficiency.</p>","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":"15 4","pages":""},"PeriodicalIF":5.9,"publicationDate":"2026-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13064846/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147522091","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The harmonies played by miR-302/367 cluster in pluripotency, reprogramming, and rejuvenation.","authors":"Melika Zamanian, Sharif Moradi, Hossein Baharvand","doi":"10.1093/stcltm/szaf072","DOIUrl":"10.1093/stcltm/szaf072","url":null,"abstract":"<p><p>The conserved, pluripotency-associated miR-302/367 cluster coordinates cell fate and aging via epigenetic, cell cycle, and signaling regulation. Highly expressed in pluripotent stem cells and silenced during differentiation, it promotes efficient somatic cell reprogramming by suppressing senescence mediators (eg, p16INK4a, p21) and replacing oncogenes such as c-Myc to minimize tumorigenic risks. Beyond pluripotency, the miR-302/367 cluster reduces oxidative stress, mitochondrial dysfunction, and fibrosis, indicating therapeutic potential in age-associated conditions such as neurodegenerative, ocular, and fibrotic diseases. This review summarizes the dual ability of miR-302/367 cluster in promoting cell state transitions and transiently resetting cellular aging to enable healthspan extension. We critically discuss the pivotal role of miR-302/367 cluster in pluripotency and reprogramming while countering aging hallmarks. Finally, we explore how combining single-miRNA therapeutics with clinically viable delivery systems (lipid nanoparticles and extracellular vesicles) can link cellular reprogramming with targeted rejuvenation therapies.</p>","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":"15 2","pages":""},"PeriodicalIF":5.9,"publicationDate":"2026-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12907026/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146202125","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Heterogeneity and optimal study design between cell lines in induced pluripotent stem cell-based cardiac disease modeling.","authors":"Renee G C Maas, Chris Denning, Joost P G Sluijter","doi":"10.1093/stcltm/szag001","DOIUrl":"10.1093/stcltm/szag001","url":null,"abstract":"<p><p>Human-induced pluripotent stem cell (hiPSC) technologies have provided access to in vitro models of inaccessible human cardiomyocytes (CMs), providing new insights into human disease mechanisms, therapy strategies, and cardiac toxicology. However, the robustness of reproducible outcomes and integration of data among research groups are hampered due to the variation between cell lines, clones, and batches-to-batch differences. These variable outcomes in hiPSC models are caused by differences in human donors, genetic stability, and experimental variability, which affect morphology, cellular heterogeneity, transcript and protein abundance, and differentiation potency. This review summarizes the usage of hiPSC-CMs obtained from multiple lines and evaluates the corresponding experimental variation between studies to perform in-depth in vitro power calculations. Our meta-analyses show that although 4 or more hiPSC lines are used in 21 published case-control studies, these reports still contain high heterogeneity between functional parameters. In specific CM readouts, the SD is >40%, meaning that the variation between different cell lines is larger than the effect of the studied mutation, drug response, or toxicity. Results indicate a need for careful selection of hiPSC lines, controls, and readout stability and these insights will further guide the power of hiPSC lines in biomedical applications.</p>","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":"15 2","pages":""},"PeriodicalIF":5.9,"publicationDate":"2026-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12866806/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146066710","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic potential of MSCs and their exosomes in hepatic Ischaemia-Reperfusion injury: a systematic review and meta-analysis of rodent studies.","authors":"Yanxi Mu, Weixiong Zhu, Wentao Ma, Yu Cheng, Bo Ren, Yusheng Cheng, Wence Zhou","doi":"10.1093/stcltm/szaf078","DOIUrl":"10.1093/stcltm/szaf078","url":null,"abstract":"<p><strong>Objective: </strong>This meta-analysis comprehensively evaluates the therapeutic efficacy and mechanisms of mesenchymal stem cells (MSCs) and their exosomes in rodent models of hepatic ischemia-reperfusion injury (HIRI), providing preclinical support for future clinical translation.</p><p><strong>Methods: </strong>In accordance with the PRISMA guidelines, we systematically searched PubMed, Web of Science, Embase, Cochrane Library, and ClinicalTrials.gov for studies published from inception to January 13, 2025, and identified 64 eligible studies. Risk of bias was evaluated using the SYRCLE tool, and Review Manager 5.4.1 was employed for meta-analysis, calculating SMD and 95%CI. Primary outcomes included liver function (ALT/AST), histopathological scores (Suzuki's score, necrotic area ratio), inflammatory cytokines (TNF-α), and apoptosis markers (c-caspase 3).</p><p><strong>Results: </strong>MSCs and their exosomes significantly ameliorated HIRI. In the 60-minute ischemia group, ALT (SMD = 3.49, P < .00001) and AST (SMD = 3.86, P < .00001) decreased, along with lower Suzuki scores (SMD = 3.12), necrotic area ratios (SMD = 3.56), and TNF-α levels (SMD = 2.83). In the 90-minute group, ALT (SMD = 4.09, P < .00001) and AST (SMD = 3.78, P < .00001) were also reduced. Mechanistically, MSCs exert therapeutic effects through antioxidative, anti-inflammatory, anti-apoptotic, and pro-regenerative pathways. Considerable heterogeneity (I2 = 52-86%) was observed, likely due to variations in dosage (1 × 105-1 × 109 cells), administration routes (intravenous/portal vein), and reperfusion durations (3-24 hours). Genetic modifications (e.g., HO-1 overexpression) further enhanced therapeutic outcomes.</p><p><strong>Conclusion: </strong>MSCs and their exosomes mitigate HIRI through multi-target mechanisms but requires standardized protocols. Future studies should prioritize large-animal validation and translational research to facilitate precision clinical application.</p>","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":"15 2","pages":""},"PeriodicalIF":5.9,"publicationDate":"2026-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12832943/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146046941","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epicardial cell activation as a paradigm shift in cardiac repair and regeneration.","authors":"Roberto Vanni, Matteo Aubry, Mauro Rinaldi, Raffaella Rastaldo, Claudia Giachino","doi":"10.1093/stcltm/szaf074","DOIUrl":"10.1093/stcltm/szaf074","url":null,"abstract":"<p><p>Cardiovascular diseases, particularly myocardial infarction, remain a leading cause of mortality globally, primarily due to the adult heart's limited regenerative capacity. Recent discoveries have highlighted the epicardium, a mesothelial layer surrounding the heart, as a critical player in cardiac repair and regeneration. During development, the epicardium plays a central role in heart formation by providing progenitor cells, structural components, and paracrine signals. Emerging evidence indicates that this developmental potential can be reactivated in the adult heart following injury. Upon activation, epicardial cells undergo epithelial-to-mesenchymal transition, proliferate, and secrete a range of paracrine factors that influence angiogenesis, inflammation resolution, and extracellular matrix remodeling. This review explores the mechanisms underlying epicardial activation, its contributions to heart development and myocardial repair, and its therapeutic potential. We discuss small molecule modulators, gene therapy, cellular therapies, and biomaterial-based approaches that aim to harness the regenerative capacity of the epicardium. These approaches, which move beyond scar tissue formation to possible regeneration, have the potential to transform the landscape of cardiac regenerative medicine. Despite promising preclinical results, however, challenges such as interindividual variability, incomplete differentiation of epicardial-derived cells, and delivery constraints must be addressed. Advances in single-cell technologies, biomaterial engineering, and translational research are paving the way for personalized and effective epicardium-based therapies. By redefining the role of the epicardium in cardiac biology, epicardial activation offers a novel paradigm for treating ischemic heart disease and heart failure.</p>","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":"15 2","pages":""},"PeriodicalIF":5.9,"publicationDate":"2026-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12907021/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146100710","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cellular iron flux measurement by micromagnetic resonance relaxometry as a critical quality attribute of mesenchymal stromal cells.","authors":"Yanmeng Yang, Meiqi Kang, Mengli Chen, Liang Cui, Zheng Yang, Jongyoon Han","doi":"10.1093/stcltm/szaf080","DOIUrl":"10.1093/stcltm/szaf080","url":null,"abstract":"<p><strong>Background: </strong>Clinical application of mesenchymal stromal cells (MSCs) for cartilage regeneration has been hampered by their poor retention of chondrogenic potential during in vitro culture, which has led to highly variable cartilage repair outcomes. Consequently, there is an urgent need for a reliable assay to predict MSC chondrogenic potential during cell manufacturing.</p><p><strong>Methods: </strong>In this study, we developed a nondestructive MSCs iron flux monitoring methodology using spent culture media, utilizing micromagnetic resonance relaxometry (µMRR). We demonstrated that the dynamics of iron uptake and release by MSCs in culture can be reliably inferred from iron concentration changes in culture medium, with an unprecedented temporal resolution (<1 hour).</p><p><strong>Results: </strong>Analysis of 3 MSC donors across 6 independent culture batches revealed a significant correlation between iron homeostasis (iron flux during culture) and chondrogenic differentiation outcomes, while a departure from iron homeostasis (significant iron uptake and accumulation) was correlated with impaired chondrogenesis. By contrast, cell proliferation, although essential for manufacturing to achieve sufficient cell numbers, did not reliably correlate with chondrogenic capacity. Furthermore, ascorbic acid supplementation during culture, which is known to promote MSCs proliferation and chondrogenic quality, regulated iron homeostasis by limiting iron flux.</p><p><strong>Conclusion: </strong>Our findings identify iron homeostasis as a potential chondrogenic-associated critical quality attribute of MSCs. This rapid, nondestructive monitoring strategy offers a promising approach to improve manufacturing efficiency and consistency by providing real-time insight into cellular iron flux. In addition, the methodology here impacts broader iron biology by providing a time-resolved iron flux measurement that is not currently available.</p>","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":"15 2","pages":""},"PeriodicalIF":5.9,"publicationDate":"2026-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12832954/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146046674","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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 stromal vascular fraction injection for radiation-induced bladder fibrosis: a first-in-human pilot study.","authors":"Roger Klein, Nerone Douglas, Asim Ejaz, J Peter Rubin, Paul Rusilko","doi":"10.1093/stcltm/szag002","DOIUrl":"10.1093/stcltm/szag002","url":null,"abstract":"<p><p>Pelvic radiotherapy can lead to loss of bladder compliance, detrusor overactivity, and superficial vascular proliferation. Animal studies have demonstrated a reduction in radiation-induced inflammation and fibrosis following administration of mesenchymal stem cell products. We performed a first-in-human pilot study to assess the safety and feasibility of intravesical adipose stromal vascular fraction injection in an 82-year-old man with a history of brachytherapy for prostate cancer. Following FDA and IRB approval, subcutaneous adipose tissue harvested under local anesthesia was immediately processed using the SVF-2 device (GID Bio). The cell product, consisting of 4.58 × 107 stromal vascular fraction cells resuspended in 20 cc/s of lactated ringers, was injected into the bladder wall using a flexible cystoscope. Urinary symptoms, urologic flow parameters, repeat cystoscopy with bladder biopsy, and MRI were employed during the 16-month follow-up period. There were no postprocedural complications. The patient reported expected symptoms of self-limited dysuria, hematuria, and flank bruising in the 2 weeks following the procedure. Urinary symptoms and flow parameters remained stable for 6 months but progressed slightly at 15 months. A repeat cystoscopy with biopsy showed stabilization of disease without concern for secondary malignancy. The patient's 12-month postprocedural MRI and 15-month urodynamics study were unchanged from prior. This study demonstrates the safety and feasibility of adipose harvest under local anesthesia, followed by point-of-care isolation and administration of an adipose-derived cell product via cystoscopic-guided intravesical injection. This pilot is foundational for further clinical studies to elucidate effective dosing and patient selection in the treatment of bladder fibrosis with cell therapy.</p>","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":"15 2","pages":""},"PeriodicalIF":5.9,"publicationDate":"2026-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12907017/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146107300","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extracellular vesicles derived from differentiated granulosa-like cells restore the ovarian function of rats with premature ovarian insufficiency.","authors":"Cheng Zou, Zelan Yang, Yan Zou, Hanyu Xiao, Yufei Deng, Jin Bai, Liaoqiong Fang, Zhibiao Wang","doi":"10.1093/stcltm/szaf081","DOIUrl":"10.1093/stcltm/szaf081","url":null,"abstract":"<p><p>Specifically differentiated cells exhibit greater therapeutic efficacy than mesenchymal stem cells (MSCs), and extracellular vesicles (EVs) present therapeutic benefits similar to those of parental cells and fewer safety issues. Ovarian granulosa cells (OGCs) play a critical role in the pathogenesis of premature ovarian insufficiency (POI), a common gynecological disease that can cause infertility and has no effective treatment. Here, we investigated whether umbilical cord mesenchymal stem cells (UCMSCs) can differentiate into ovarian granulosa-like cells (GLCs) and whether GLC-EVs are more effective in restoring ovarian function than UCMSC-EVs are in POI model rats. Here, we differentiated rat UCMSCs (rUCMSCs) into GLCs in vitro using cytokines and hormones and isolated GLC-EVs. We then used chemotherapy-induced POI model rats to verify the ability of GLC-EVs to repair ovarian function. We found that GLCs/GLCs-EVs expressed granulosa cell markers (FOXL2 and FSHR). We demonstrated that GLC-EVs outperformed rUCMSC-EVs by restoring the estrous cycle and ovarian morphology, increasing the number of follicles, regulating serum hormone levels, and restoring fertility in POI model rats. Mechanistically, GLC-EVs showed enhanced ovarian tropism. Proteomic analysis identified PLAU as a key component of GLC-EVs, and subsequent antibody blockade experiments demonstrated that PLAU contributes to primordial follicle activation through promoting FOXO3A phosphorylation (pFOXO3A). This study provides the first proof that EVs derived from differentiated cells enhance therapeutic precision for POI, improve the tissue targeting of EV therapy, and provide a generalized strategy for clinical cell-free therapy.</p>","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":"15 2","pages":""},"PeriodicalIF":5.9,"publicationDate":"2026-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12832956/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146046647","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}