Stem Cells Translational Medicine最新文献

{"title":"Human umbilical cord mesenchymal stem cells alleviate brain injury and promote neuroregeneration via BDNF/TrkB/CREB/PI3K-Akt pathway in preterm rats with intraventricular hemorrhage.","authors":"Mingyou Yu, Ziyi Zhang, Xuxian Wu, Baoying Zhang, Yang Hu, Changge Wei, Miao Ran, Manni Cao, Jinhui Zhang, Xueli Ding, Yan Wang, Can Liu, Maoqiong Chen, Jianwei Xu","doi":"10.1093/stcltm/szag086","DOIUrl":"10.1093/stcltm/szag086","url":null,"abstract":"<p><strong>Objective: </strong>To explore the neuroprotective effect and molecular mechanism of human umbilical cord mesenchymal stem cells (hUC-MSCs) in preterm rats with intraventricular hemorrhage (IVH), and provide experimental basis for clinical treatment of neonatal IVH.</p><p><strong>Methods: </strong>Tissue block adherence method was used to isolate and culture hUC-MSCs, and P4 Sprague-Dawley premature rats were divided into sham, IVH model, and hUC-MSC treatment groups. Collagenase VIIS was injected to establish IVH model, and hUC-MSCs were injected into lateral ventricles. Cell colonization, body weight, neurobehavior, brain histology, apoptosis, and related molecular indicators were detected via fluorescence tracking, behavioral tests, staining, RT-PCR, Western blot (WB), and ELISA. Bioinformatics combined with ANA12 blocking assay verified core pathways.</p><p><strong>Results: </strong>hUC-MSCs survived in rat brain for at least 7 days. Compared with the model group, the treatment group gained weight faster, neurobehavioral function was markedly improved, neuronal apoptosis decreased sharply, and brain tissue damage was alleviated. hUC-MSCs up-regulated anti-apoptotic, anti-inflammatory, antioxidant and neurogenesis-related molecules and activated BDNF/TrkB/CREB/PI3K-Akt pathway; TrkB blockade reversed all protective effects.</p><p><strong>Conclusion: </strong>hUC-MSCs exert multi-target neuroprotection by activating BDNF/TrkB/CREB/PI3K-Akt pathway, which offers a novel strategy for IVH treatment in preterm infants.</p>","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":"15 11","pages":""},"PeriodicalIF":5.9,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13675110/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149207408","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":"Kidney organoids as a platform to study plasminogen-induced injury and uPA-based therapies.","authors":"Marina de Cos, Samuel Mon-Wei Yu, Jacob Wright, Nanditha Anandakrishnan, Kristin Meliambro, Jenny S Wong, Evren Azeloglu, Kirk N Campbell","doi":"10.1093/stcltm/szag078","DOIUrl":"10.1093/stcltm/szag078","url":null,"abstract":"<p><p>Urinary plasminogen has been implicated in the progression of proteinuric kidney diseases, yet its direct role in mediating injury along the nephron remains incompletely understood. Experimental models commonly used to study plasminogen-mediated damage are limited by incomplete phenotypic fidelity or interspecies differences, hindering translational relevance. Here, we used kidney organoids generated from H9 human embryonic stem cells to investigate the effects of plasminogen exposure and to evaluate urokinase-type plasminogen activator (uPA) inhibition with amiloride as a therapeutic strategy. Kidney organoids were exposed to plasminogen in the presence or absence of amiloride, and uPA activity was quantified using a fluorescence-based assay. Compartment-specific injury was assessed by confocal microscopy, automated image analysis, and AI-assisted nuclear segmentation, while targeted transcriptomic changes were evaluated using bulk quantitative PCR. Plasminogen exposure induced glomerular injury, characterized by reduced podocalyxin, nephrin, podocin, and WT1 expression, decreased glomerular cell density, and increased apoptosis. Proximal tubules exhibited reduced LTL and megalin expression, with increased KIM-1, whereas distal tubules were relatively preserved. Amiloride effectively inhibited uPA activity and partially restored podocyte and proximal tubular marker expression, but did not prevent apoptosis, indicating incomplete protection against plasminogen-induced injury. These findings support preferential plasminogen-induced injury along the glomerular-proximal tubular axis and highlight the utility of human kidney organoids for modeling this process, while underscoring the need for further validation and broader molecular profiling to strengthen their application in mechanistic studies and therapeutic discovery.</p>","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":"15 10","pages":""},"PeriodicalIF":5.9,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13593615/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149017352","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":"Single-cell transcriptomics reveals critical role of CD74 in bone marrow-derived mesenchymal stem cells.","authors":"Qinqin Xu, Carson Curtis, Jiahao Zhang, Arjun Verma, Aaron J Sheppard, Jeffrey Deng, Hicham Drissi, Shane Barton, Patrick Massey, Yufeng Dong","doi":"10.1093/stcltm/szag082","DOIUrl":"10.1093/stcltm/szag082","url":null,"abstract":"<p><strong>Background: </strong>Human bone marrow aspirates have been widely used for skeletal tissue regeneration. However, clinical outcomes of the tissue repair after transplantation are variable.</p><p><strong>Methods: </strong>In this study, we analyzed the molecular signatures and osteogenic differentiation potential of bone marrow-derived mesenchymal stromal cells (BMSCs) from different donors.</p><p><strong>Results: </strong>Our results clearly showed that BMSCs isolated from different patients exhibited different osteogenic capacities and growth rates. Moreover, single-cell RNA sequencing revealed that these BMSCs expressed elevated levels of genes associated with early osteogenesis, chondrogenesis, and adipogenesis. Differentially expressed genes related to cell cycles were enriched in clusters from all 5 different samples, suggesting these genes play an important role in BMSC maintenance and differentiation. More importantly, the BMSCs with the lowest osteogenic differentiation potential showed a dramatic decrease in the expression of cell surface protein CD74 when compared to other osteogenic genes. Knockdown of CD74 in BMSCs with high osteogenic potential significantly reduced their osteogenic capacity.</p><p><strong>Conclusions: </strong>These findings suggest that CD74 is a novel predictive marker of outcomes following BMSC transplantation. Furthermore, CD74-high BMSCs may represent a subpopulation of bone marrow cells responsible for bone marrow aspirate-mediated tissue regeneration.</p>","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":"15 10","pages":""},"PeriodicalIF":5.9,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13588712/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149002559","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":"JAG1 c.1615C > T mutation impairs bile duct regeneration but not differentiation in hepatic organoids derived from a patient with Alagille syndrome.","authors":"Zirui Wan, Haiyan Zhang, Lu Zhang, Xiaofang Cao, Lisha An, Bin Wang, Jingyun Guan, Jinlin Jia, Chen Liu, Xiaohua Jin, Yue Li, Guohua Liu, Xu Ma","doi":"10.1093/stcltm/szag073","DOIUrl":"10.1093/stcltm/szag073","url":null,"abstract":"<p><strong>Objective: </strong>Alagille syndrome (ALGS) is an autosomal dominant disorder caused primarily by mutations in JAG1. Intrahepatic bile duct paucity is the most consistently reported feature of ALGS; however, the mechanisms associated with biliary defects remain unclear.</p><p><strong>Methods: </strong>Here, we reverted or introduced the JAG1 c.1615C > T mutation to patient-specific induced pluripotent stem cells (iPSC) or human embryonic stem cells (hESCs) using base editors to generate isogenic cell lines and examine cellular phenotypes associated with this mutation in hepatic organoids.</p><p><strong>Results: </strong>We observed that JAG1 mutant lines showed no significant differences in cholangiocyte differentiation or function compared with the corresponding wild-type lines. By contrast, organoids derived from JAG1 mutant cells showed reduced cell survival, attenuated responsiveness to VEGF stimulation, and abnormal cell polarity.</p><p><strong>Conclusions: </strong>These findings offer a new insight into the biliary pathologies in ALGS and provide theoretical support for future proof-of-concept studies of novel therapeutic approaches for ALGS.</p>","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":"15 10","pages":""},"PeriodicalIF":5.9,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13593616/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149017375","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":"Haploidentical HSCT vs immunosuppressive therapy for severe aplastic anemia in patients aged 40-65 years: a retrospective comparative study.","authors":"Sheng-Nan Gao, Jin-Song Jia, Xiao-Jun Huang, Yuan-Yuan Zhang, Ting-Ting Han, Hai-Xia Fu, Yun He, Yao Chen, Jing-Zhi Wang, Xiao-Dong Mo, Yu-Qian Sun, Wei Han, Yu Wang, Xiao-Hui Zhang, Lan-Ping Xu, Zheng-Li Xu","doi":"10.1093/stcltm/szag076","DOIUrl":"https://doi.org/10.1093/stcltm/szag076","url":null,"abstract":"<p><p>Severe aplastic anemia (SAA) is a life-threatening hematological disorder, and the optimal treatment for patients aged ≥40 years remains controversial. This retrospective study aims to conduct a comparative analysis of the efficacy of immunosuppressive therapy (IST) versus haploidentical hematopoietic stem cell transplantation (haplo-HSCT) specifically in elderly patients. To minimize selection bias, propensity score matching (PSM) was performed to pair samples based on age and Eastern Cooperative Oncology Group score, thereby addressing treatment responses and survival outcomes while ensuring balanced baseline characteristics between the 2 groups. The study reveals that while overall survival (OS) rates were similar (69.6% ± 13.3% vs. 68.6% ± 12.1%, P = 0.80), haplo-HSCT significantly outperformed IST in terms of failure-free survival (FFS) rates (68.7% ± 12.1% vs. 46.5% ± 20.2%, P = 0.025). Multivariate Cox regression analysis confirmed that treatment modality and disease severity were independent predictors of FFS. These findings support haplo-HSCT as a viable first-line treatment option for appropriately selected elderly SAA patients, providing evidence for treatment options in patients with SAA aged 40 and above.</p>","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":"15 10","pages":""},"PeriodicalIF":5.9,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13629439/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149115005","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":"Fate of long-term culture on hepatocyte-like cells generated from human adipose-derived mesenchymal stem cells.","authors":"Mengling Ji, Yu Saito, Yuhei Waki, Shuhai Chen, Tetsuya Ikemoto, Takayuki Noma, Hiroki Teraoku, Shinichiro Yamada, Yuji Morine, Mitsuo Shimada","doi":"10.1093/stcltm/szag061","DOIUrl":"10.1093/stcltm/szag061","url":null,"abstract":"<p><strong>Background: </strong>We previously established a 21-day protocol to generate hepatocyte-like cells (HLCs) from adipose-derived stem cells and are conducting preclinical studies toward their clinical application in liver failure. This study examined how long HLCs maintain viability and hepatocyte-specific functions after differentiation.</p><p><strong>Methods: </strong>Adipose-derived stem cells (2.0 × 106) were differentiated into HLCs using a 3-step protocol for 21 days. After differentiation, cells were either transferred to transplantation medium (TM), used clinically, or maintained in step-3 differentiation medium (DM). Cell viability, hepatocyte-specific gene expression, and functional assays were performed on days 24 and 28. Because bile acid synthesis may induce cytotoxicity during extended culture, the expression of bile acid-related genes and transporters was evaluated on day 35.</p><p><strong>Results: </strong>Viability markedly decreased when HLCs were transferred to TM, whereas cells maintained in DM preserved viability up to day 28. The expression of mature hepatocyte markers (AAT, ALB, CPS1, and OTC) remained comparable between days 21 and 28. Hepatocyte functions, including CYP3A4 activity and ammonia metabolism, were also sustained in DM-cultured HLCs. Importantly, genes involved in bile acid synthesis and transport, which could contribute to cytotoxicity during prolonged culture, were undetectable even after 28 days.</p><p><strong>Conclusion: </strong>HLCs generated using our protocol maintained viability and hepatocyte-specific functions for at least 28 days when cultured in DM, without detectable bile acid-related gene expression. These findings suggest that transplantation timing can be flexibly adjusted for at least 1 week after the completion of differentiation.</p>","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":"15 10","pages":""},"PeriodicalIF":5.9,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13588577/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149002520","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":"Effect of intrathecal injection of mesenchymal stem cell-neural progenitors on cerebrospinal fluid biomarkers in progressive multiple sclerosis.","authors":"Violaine K Harris, Andrea Jiang, Sofia Ricciarini, Nikki Jagid, Maureen McCormick, Cara Kizilbash, Saud A Sadiq","doi":"10.1093/stcltm/szag083","DOIUrl":"10.1093/stcltm/szag083","url":null,"abstract":"<p><p>Mesenchymal stem cell-neural progenitors (MSC-NP) are a bone marrow mesenchymal stem cell-derived population of cells with trophic and immunomodulatory properties with therapeutic potential in multiple sclerosis (MS). Early phase clinical trials have investigated the safety and efficacy of intrathecal administration of autologous MSC-NPs in people with progressive MS. To better understand the biological response to MSC-NP treatment, we analyzed cerebrospinal fluid (CSF) biomarkers in 2 separate cohorts of trial subjects with secondary progressive or primary progressive MS from both a phase 2 trial (n = 50) and an expanded access trial (n = 43) who received repeated administrations of autologous MSC-NPs. Candidate biomarkers identified through proteomic screening were validated in both cohorts, revealing a panel of 4 biomarkers (CCL2, C-C motif chemokine ligand-2; MMP9, matrix metalloproteinase-9; SCF, stem cell factor/c-kit ligand; and CHIT1, chitotriosidase-1) that were significantly changed in CSF but not serum following treatment. Other MS biomarkers neurofilament light and glial fibrillary acidic protein were unchanged following treatment but correlated with age, and both age and Expanded Disability Status Scale (EDSS), respectively. The specific biomarker changes observed following MSC-NP injections suggest distinct biological effects following MSC-NP treatment. These biomarkers help define the pharmacodynamic response to MSC-NP treatment as well as guide the design of future clinical studies.</p>","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":"15 10","pages":""},"PeriodicalIF":5.9,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13585449/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148991522","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":"Up to 19-year cryopreservation does not impair hematopoietic progenitor function in cord blood: a 1129-unit analysis from the largest Korean public cord blood bank.","authors":"Eun Youn Roh, Hye Ryun Lee, Sue Shin, Jong Hyun Yoon, Nam-Hee Kim, Hyun-Woong Park, Byoung Jae Kim","doi":"10.1093/stcltm/szag075","DOIUrl":"10.1093/stcltm/szag075","url":null,"abstract":"<p><strong>Background: </strong>Whether umbilical cord blood (UCB) quality is maintained during decades of cryopreservation is critical for public banking policy. We analyzed post-thaw quality of 1129 UCB units cryopreserved for up to 19 years at Korea's largest public cord blood bank and examined implications for shelf-life policy.</p><p><strong>Methods: </strong>UCB units manually volume-reduced and cryopreserved between 2006 and 2025 underwent pre-transplant testing using their attached integral segments (median storage 6.5 years; range 16 days-19.0 years). Associations between storage duration and 19 quality indicators and 13 paired pre-/post-thaw complete blood count parameters were analyzed by Spearman correlation (ρ) before and after adjusting for era effects (processing and testing dates) to separate genuine storage effects from longitudinal analytical variation. Predictors of colony-forming unit (CFU) were ranked by univariate correlation and a Random Forest machine-learning model. Compliance with German/FACT-NetCord pre-transplant criteria was assessed.</p><p><strong>Results: </strong>Associations between storage duration and quality indicators were modest before adjustment (|ρ| ≤ 0.4) and were largely abolished once differences in testing era were taken into account: the storage-duration correlations for viable CD45+ and viable CD34+ both lost significance, as did CFU/CD34 + (P = .327). The post-thaw CD34+ count was the strongest predictor of CFU. Testing date, although ranked only seventh by simple correlation, rose to second in the Random Forest model, indicating an era effect not captured by pairwise analysis. The composite pre-transplant criteria pass rate was 96.2%, remaining above 93% across all storage bins.</p><p><strong>Conclusions: </strong>After up to 19 years of cryopreservation, per-CD34+ colony-forming capacity is preserved. A test-based shelf-life policy is more evidence-based than a predetermined expiration limit.</p>","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":"15 9","pages":""},"PeriodicalIF":5.9,"publicationDate":"2026-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13505624/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148819435","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":"Intranasal stem cell treatment ameliorates neuroinflammation and myelin aberrations in fetal growth-restricted rat pups.","authors":"Judit Alhama-Riba, Anastasija Aleksić, Nicola Pelizzi, Freek E Hoebeek, Caroline G M de Theije, Cora H A Nijboer","doi":"10.1093/stcltm/szag081","DOIUrl":"10.1093/stcltm/szag081","url":null,"abstract":"<p><p>Fetal growth restriction (FGR), a condition in which a fetus fails to reach its full growth potential, affects approximately 30 million infants worldwide each year and increases the risk of long-term neurodevelopmental deficits. Currently, no effective therapies exist to mitigate FGR-induced neurological impairments. Mesenchymal stem cells (MSCs) have emerged as a promising neuroregenerative therapeutic approach. Here, we used the reduced uterine perfusion pressure (RUPP) rat model of chronic placental hypoperfusion-induced FGR. We explored, for the first time, intranasal MSC administration in the early postnatal period in growth-restricted offspring as a minimally invasive and clinically feasible cell delivery approach. RUPP pups received human Wharton's jelly-derived MSCs or vehicle intranasally at postnatal day 5 (P5) or P10, and neuropathological outcomes were assessed at P20. Pups from sham-operated dams served as controls. Intranasal MSC treatment, particularly at the early postnatal treatment timepoint (P5), ameliorated key neuropathological outcomes, as evidenced by improved brain weight and cortical myelination, enhanced oligodendrocyte maturation, and dampened microglial activation compared to vehicle-treated RUPP pups. Functional impairments, measured between P13 and P56 by eye opening, grip strength, and foot faults on the tapered beam walk, showed no significant improvement. Our findings provide proof-of-concept that early-life stem cell therapy provides histological improvements in RUPP-induced brain abnormalities. Although further optimization is needed to establish whether these effects translate into functional benefits, intranasal MSCs represent a promising, minimally invasive neuroregenerative strategy with potential clinical relevance for newborns affected by chronic placental insufficiency-induced FGR.</p>","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":"15 9","pages":""},"PeriodicalIF":5.9,"publicationDate":"2026-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13570797/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148956588","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":"Exosome therapy for knee osteoarthritis: a network meta-analysis based on rat models.","authors":"Yixiang Zhao, Haochuan You, Xiuyuan Wang, Xiping Dou, Jiangying Zhang, Yuzhe He, Lei Chen, Fei Huang, Yayi Xia","doi":"10.1093/stcltm/szag069","DOIUrl":"https://doi.org/10.1093/stcltm/szag069","url":null,"abstract":"<p><strong>Objective: </strong>To compare the therapeutic effects of exosomes from different cell sources and doses in rat knee osteoarthritis models using network meta-analysis, and to identify potential optimal strategies for preclinical optimization and clinical hypothesis generation.</p><p><strong>Methods: </strong>A systematic search of PubMed, Web of Science, Embase, and Scopus identified 27 eligible randomized controlled trials (456 rats). Traditional random-effects meta-analysis and frequentist network meta-analysis were conducted. Treatments were ranked using SUCRA values.</p><p><strong>Results: </strong>A total of 27 studies were included, comprising 456 rats. Traditional meta-analysis revealed that exosome therapy significantly reduced joint cartilage histopathological damage (reduced OARSI score: SMD = -3.78, 95% CI: -4.76, -2.80), promoted type II collagen synthesis (SMD = 3.41, 95% CI: 1.87, 4.95), and suppressed the expression of the inflammatory cytokine IL-1β (SMD = -3.26, 95% CI: -4.08, -2.44). Network meta-analysis further indicated that under high-dose conditions (≥100 μg), exosomes derived from human amniotic fluid stem cells (hAFSCs-Exo) and human umbilical cord mesenchymal stem cells (hUCMSCs-Exo) ranked highest in relative efficacy for improving the OARSI score. hUCMSCs-Exo also demonstrated the most potent anti-inflammatory effect by reducing IL-1β. Overall, exosome therapy exhibited a dose-related trend in efficacy, with high-dose transplantation showing higher probabilistic SUCRA rankings across most outcome measures. However, assessment of publication bias revealed marked asymmetry; after trim-and-fill correction, the effect size for type II collagen expression decreased from SMD = 3.41 to 1.26, suggesting that the magnitude of the treatment effect may have been overestimated. This overestimation reduces the certainty of the observed treatment effects. Despite the presence of publication bias and methodological limitations, the main conclusions remained statistically robust after trim-and-fill correction.</p><p><strong>Conclusion: </strong>Current evidence from rat models suggests that exosome therapy may substantially ameliorate the pathological progression of KOA, with exosomes derived from early developmental tissues, particularly hAFSCs-Exo and hUCMSCs-Exo, showing favorable chondroprotective and anti-inflammatory effects in the probabilistic ranking when administered at high doses. Nevertheless, the findings from publication bias and trim-and-fill analyses indicate that the existing effect sizes are likely overestimated. These results require confirmation in larger-scale, methodologically more rigorous preclinical studies.</p>","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":"15 9","pages":""},"PeriodicalIF":5.9,"publicationDate":"2026-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13485348/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148798116","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}