Stem Cells Translational Medicine最新文献

{"title":"Ckb-Cryab-Drp1 axis enhances BMSC osteogenic differentiation and mouse alveolar bone healing through mitochondrial fission modulation.","authors":"Mingxi Wang, Long Wang, Jingchan Wang, Shan Gao, Guoqing Li, Chunbo Tang","doi":"10.1093/stcltm/szag056","DOIUrl":"10.1093/stcltm/szag056","url":null,"abstract":"<p><p>Repairing bone defects resulting from trauma, infection, or tumor resection remains a significant challenge in clinical practice. Particularly in the oral and maxillofacial region, achieving predictable bone regeneration is especially difficult due to the complex anatomical structure and the critical need for optimal aesthetic and functional outcomes. A deeper understanding of the molecular mechanisms governing osteogenic differentiation is therefore essential to develop effective strategies for bone repair. Although creatine kinase B (Ckb) is known for its role in energy metabolism, its function in bone regeneration remains poorly understood. In this investigation, we found that Ckb is specifically expressed in jaw mesenchymal cells. Functional assays demonstrated that Ckb promoted osteogenic differentiation of bone marrow mesenchymal stem cells in vitro. Consistently, Ckb overexpression promoted alveolar bone healing in a mouse tooth-extraction model, while Ckb knockdown impaired bone regeneration. We discovered that Ckb localized to mitochondria and enhanced mitochondrial fission by increasing dynamin-related protein 1 (Drp1) Ser616 phosphorylation. The pro-osteogenic impact of Ckb was reduced by pharmacologically inhibiting mitochondrial fission with Mdivi-1. This result was replicated by Drp1 knockdown, indicating that Drp1 is essential for Ckb-mediated osteogenesis. Transcriptome sequencing identified αB-crystallin (Cryab) as a key downstream effector of Ckb, and co-immunoprecipitation confirmed a physical interaction between Ckb and Cryab. Crucially, Cryab overexpression rescued the osteogenic and mitochondrial dysfunction caused by Ckb knockdown. Collectively, our research reveals a unique Ckb-Cryab-Drp1 axis that controls mitochondrial dynamics to coordinate osteogenesis, offering a molecular basis for guiding MSC-based bone regeneration techniques.</p>","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":"15 8","pages":""},"PeriodicalIF":5.9,"publicationDate":"2026-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13441178/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148679729","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":"Functional characterization of human iPSC-derived sensory neuron processes in microfluidic cultures.","authors":"Laura Kleckner, Omar Mossad, Anil Kumar Kalia, Ramin Raouf","doi":"10.1093/stcltm/szag065","DOIUrl":"10.1093/stcltm/szag065","url":null,"abstract":"<p><p>Rodent cell culture models have long underpinned research into nociceptive signaling; however, their limited recapitulation of human nociceptor biology has created a translational gap in analgesic development. While primary human sensory neurons are relevant, their use is hampered by scarcity, ethical constraints, donor variability, and difficulties in long-term culture. Furthermore, conventional cultures lack the compartmentalization needed to study sensory neuron processes and fail to recapitulate the synaptic connectivity between sensory and spinal cord neurons, limiting their translational relevance. To address these limitations, we utilized a microfluidic platform enabling compartmentalized culture of human induced pluripotent stem cell (hiPSC) derived sensory neurons (hiPSC-SNs) to study the function of their processes. We also demonstrate the feasibility of microfluidic co-cultures of hiPSC-SN with human iPSC-derived cortical excitatory neurons (hiPSC-CNs) as a basis for future development of models for sensory-to-CNs communication circuit. Using optimized protocols, we maintained stable microfluidic cultures and confirmed expression of pain-relevant sodium channels (Nav1.7, Nav1.8) in hiPSC-SN in both mono- and co-culture configurations. Leveraging this compartmentalized platform, we demonstrate that pharmacological blockade of Nav1.7 and Nav1.8 inhibits signal propagation along sensory neuron processes. We also demonstrate that growth factors modulate excitability of these processes. This functional validation underscores the platform's capability to investigate signal transmission along human sensory processes and demonstrates its potential for modelling more complex cellular interactions. Thus, we present a human iPSC-based microfluidic culture model that enables detailed study of sensory neuron processes and assessment of analgesics targeting nociceptive transmission, offering a significant advance toward analgesic drug discovery.</p>","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":"15 8","pages":""},"PeriodicalIF":5.9,"publicationDate":"2026-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13453313/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148702277","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":"Markers of beta cell and alpha cell mass in human stem cell-generated implants with glycemic control at human setpoint.","authors":"Kaat De Groot, Krista Suenens, Geert Stangé, Zhidong Ling, Diedert De Paep, Eline Segers, Evert Kroon, Bart Keymeulen, Daniel Jacobs-Tulleneers-Thevissen, Daniel Pipeleers","doi":"10.1093/stcltm/szag068","DOIUrl":"https://doi.org/10.1093/stcltm/szag068","url":null,"abstract":"<p><p>Human stem cell (SC)-generated beta cell implants represent a potential cure for type 1 diabetes. Studies in rodents and patients showed that they can establish a glucose-regulated source of insulin in recipients with depleted pancreatic beta cell mass. Their therapeutic significance is, however, determined by their capacity to restore glycemic control by the human glucostat. It is so far unknown which implant characteristics are needed for this key endpoint. The present study addresses this question in mice. SC-derived preparations with a defined beta cell dose and alpha cell proportion were implanted in the epididymal fat pad of normoglycemic SCID/beige mice (mouse glucostat basal glycemia 166 mg/dL). At post-transplant week 20, 12/25 recipients reached glycemic control at the human glucostat (glycemia ≤ 90 mg/dL) following a time-dependent increase of basal and glucose-induced plasma human C-peptide and decrease of mouse C-peptide towards under detection limit. Formation of their functional human beta cell mass was preceded by formation of a human alpha cell mass that became the source for circulating glucagon and a contributor to glycemic control. The insulin content of the implants reached the values in the pancreas of control mice and were thus identified as in situ markers for implants that established the glycemic endpoint. Co-existence with a functional alpha cell mass places alpha cell formation as a potential additional component for achieving the goal. Our study also demonstrates the relevance of using normoglycemic mice to assess stem cell therapy protocols for beta cell replacement.</p>","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":"15 8","pages":""},"PeriodicalIF":5.9,"publicationDate":"2026-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13475381/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148761992","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":"Patient-specific iPSC-derived ECs identify QKI-7 as a key regulator of endothelial dysfunction and potential therapeutic target in diabetes.","authors":"Victoria A Cornelius, Jenna Fulton, Clare Donaghy, Stuart McKeown, Hojjat Naderi-Meshkin, Shu-Dong Zhang, Wiwit Ananda Wahyu Setyaningsih, Andrew Yacoub, Anna Zampetaki, Alan W Stitt, Noemi Lois, David J Grieve, Andriana Margariti","doi":"10.1093/stcltm/szag057","DOIUrl":"10.1093/stcltm/szag057","url":null,"abstract":"<p><p>Diabetic vascular complications remain a major cause of morbidity and mortality, yet the molecular mechanisms underlying endothelial dysfunction in diabetes remain incompletely understood. Endothelial dysfunction is a key contributor to vascular pathology, and patient-derived induced pluripotent stem cell-derived endothelial cells (iPSC-ECs) provide a human platform to investigate disease-associated endothelial phenotypes under controlled conditions. Here, we identify the RNA-binding protein Quaking-7 (QKI-7) as a key regulatory factor associated with endothelial dysfunction in patient-derived iPSC-ECs. Using cells derived from diabetic and non-diabetic donors maintained under standard culture conditions, we demonstrate that elevated QKI-7 expression is associated with reduced expression of endothelial homeostatic genes (COL4A2, JUN, TMEM184A, and PPP1R15A) and impaired angiogenic capacity, including reduced tube formation. Importantly, these findings were further validated in three-dimensional blood vessel organoid models, supporting the relevance of QKI-7-associated endothelial phenotypes in a more physiologically complex vascular system. Connectivity mapping identified FDA-approved compounds, including simvastatin, halcinonide, and retinoic acid, as potential modulators of QKI-7-associated pathways. Functional validation in iPSC-ECs demonstrated that these compounds reduce QKI-7 expression and improve endothelial functional readouts. Together, these findings identify QKI-7 as a regulatory node associated with endothelial dysfunction in patient-derived iPSC-ECs and highlight the utility of human iPSC-based vascular models for identifying candidate therapeutic strategies. While these models capture endothelial phenotypes associated with diabetic donor origin, further studies in more complex in vivo systems will be required to establish causal relevance to vascular disease.</p>","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":"15 8","pages":""},"PeriodicalIF":5.9,"publicationDate":"2026-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13446219/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148685901","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":"From evidence to practice: factors influencing the implementation of cord blood treatment for cerebral palsy in the United States.","authors":"Madison C B Paton, Joanne Kurtzberg, Jessica Sun, Sarah Reedman, Remy Blatch-Williams, Michael Fahey, Iona Novak, Megan Finch-Edmondson","doi":"10.1093/stcltm/szag074","DOIUrl":"10.1093/stcltm/szag074","url":null,"abstract":"<p><strong>Background and aims: </strong>Cord blood infusion is an emerging treatment for cerebral palsy (CP) currently offered in the United States through clinical trials and an expanded access pathway. This study aimed to understand the barriers and facilitators influencing implementation of cord blood treatment for CP, to help inform future implementation efforts.</p><p><strong>Methods: </strong>Semi-structured interviews were conducted with US professionals involved in the cord blood treatment program for CP at Duke University and a collaborator site. Data were analyzed using reflexive thematic analysis.</p><p><strong>Results: </strong>From 16 interviews, 5 themes were identified capturing patterned barriers and enablers. Key facilitators included boundary-spanning clinical leadership, interprofessional coordination, dedicated resourcing, responsiveness to community demand, an established safety profile, and a strong research culture. Barriers included the need for cross-disciplinary expertise, uncertainty regarding efficacy evidence, funding and regulatory constraints, and system-level challenges. Participants described that many barriers were overcome to establish the program, while acknowledging that others may persist and are context dependent.</p><p><strong>Conclusions: </strong>Findings highlight that implementation of cord blood treatment for CP is feasible within specialized settings but contingent on local infrastructure, governance, and workforce capacity. Identified facilitators align with established implementation strategies and offer transferable insights, while underscoring the need for regulatory approval, ethical oversight, and system-level supports to enable equitable and sustainable access to emerging regenerative therapies for CP.</p>","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":"15 8","pages":""},"PeriodicalIF":5.9,"publicationDate":"2026-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13453308/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148702279","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":"A human iPSC-derived 3D spinal cord organoid model to study radiation-induced neural injury.","authors":"Yifei Jiang, Xubo Li, Jingguang Zeng, Shiju Chen, Runtao Zhou, Yixun Wu, Ganggang Kong, Fawei Liao, Bo Wang, Fangze Qi, Cheng Gu, Shiyi Yin, Qiguang Pang, Weidong Mu, Qingtang Zhu, Canbin Zheng","doi":"10.1093/stcltm/szag042","DOIUrl":"10.1093/stcltm/szag042","url":null,"abstract":"<p><strong>Background: </strong>Radiation therapy remains a cornerstone in the treatment of primary and metastatic tumors; however, its efficacy is limited by the spinal cord's high sensitivity to radiation-induced injury. To better understand the mechanisms underlying spinal cord radiosensitivity, we developed a three-dimensional human spinal cord organoid model derived from human-induced pluripotent stem cells using a neuroectodermal differentiation protocol that closely mimics embryonic spinal cord development.</p><p><strong>Methods: </strong>Mature spinal cord organoids were exposed to a clinically relevant 2 Gy dose of ionizing radiation, and subsequent assessments included evaluation of DNA damage, astrocytic response, and neuronal functionality.</p><p><strong>Results: </strong>The organoids successfully recapitulated key features of spinal cord development, including neural differentiation, spontaneous electrophysiological activity, and functional maturation. Radiation exposure led to pronounced DNA double-strand breaks, particularly in SOX2-expressing progenitor cells. Astrocyte hyperplasia was evident through increased GFAP expression, indicating a reactive gliosis response. Electrophysiological analysis revealed a marked reduction in spike frequency and burst activity, indicative of impaired neuronal function. Although partial recovery was observed over time, functional deficits persisted, suggesting sustained damage.</p><p><strong>Conclusion: </strong>This human spinal cord organoid model offers a physiologically relevant platform for studying radiation-induced spinal cord injury and provides valuable insights into the cellular and functional consequences of radiation exposure. It holds significant potential for advancing neuroprotective strategies and therapeutic interventions targeting radiation-induced damage in the central nervous system.</p>","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":"15 8","pages":""},"PeriodicalIF":5.9,"publicationDate":"2026-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13391157/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148563027","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":"Insulin gene-modified 3D stem cells for enhanced islet regeneration and systemic reversal of type 1 diabetes.","authors":"Qian Li, Xiao Ma, Kefei Yuan, Jiaxin Li, Li Fu, Nanxi Liu, Jianchuan Hu, Xiangzheng Chen, Yanna Zhang, Xiancheng Chen, Yong Zeng, Zhen Wang","doi":"10.1093/stcltm/szag054","DOIUrl":"10.1093/stcltm/szag054","url":null,"abstract":"<p><p>Type 1 diabetes (T1D) is a chronic autoimmune disease characterized by the destruction of pancreatic β cells, leading to lifelong insulin dependence and an increased risk of severe complications. Three-dimensional stem cells (3D SCs) culture systems have emerged as a superior alternative by more accurately mimicking the in vivo microenvironment and enhancing stemness maintenance, regenerative efficiency, and paracrine secretion. However, studies exploring the application of 3D SCs in T1D remain limited. Here, we developed a novel serum- and cytokine-free orbital-shaking system. It enables efficient and large-scale reprogramming of somatic cells into 3D embryonic-like stem cell spheroids (Sph-Es) characterized by robust pluripotency and improved safety. To enhance therapeutic utility, Sph-Es were irradiated and transduced with INS-expressing adenoviral vectors to generate Sph-R-Ins, allowing transient insulin production without permanent genomic modification. In STZ-induced T1D mice, Sph-R-Ins improved glycemic control and glucose tolerance and increased mouse insulin and C-peptide responses, indicating improved endogenous islet function. Donor-cell tracking analyses showed no pancreatic engraftment, supporting an indirect mode of action. Additional transcriptomic, immunological, and ex vivo studies indicated that the therapeutic benefit was accompanied by ECM-related signaling changes, reduced inflammatory infiltration, enhanced M2 macrophage polarization and Treg-associated immune regulation, improved metabolic signaling, and spheroid-derived paracrine support of islet function. Together, these findings establish a mechanically guided 3D stem cell-gene therapy platform with both endocrine and immunometabolic benefits in T1D.</p>","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":"15 8","pages":""},"PeriodicalIF":5.9,"publicationDate":"2026-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13441176/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148680004","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":"First evidence of the circulation of induced pluripotent stem cell-derived platelets in humans.","authors":"Kazumasa Takao, Yoshihiro Kumagae, Junya Kanda, Hidenori Hirose, Hiromichi Konno, Tomoyuki Inoue, Yuya Sato, Yasuko Hazama, Masaichi Hasegawa, Asano Asami, Mitsuhiro Nishimura, Akira Sawaguchi, Akifumi Takaori-Kondo, Kenichi Akamatsu","doi":"10.1093/stcltm/szag067","DOIUrl":"10.1093/stcltm/szag067","url":null,"abstract":"<p><p>Platelet products are essential for preventing and treating bleeding in patients with thrombocytopenia. However, their short shelf life and reliance on voluntary blood donations pose significant challenges to maintaining a stable supply. To overcome these limitations, induced pluripotent stem cell-derived platelets (iPSC-PLTs) have emerged as a promising alternative. The clinical application of iPSC-PLTs succeeded in demonstrating safety in an autologous transfusion setting; however, allogeneic applications remain unexplored. Here, we report the world's first clinical evaluation of an allogeneic iPSC-PLT product. An immortalized megakaryocyte cell line (imMKCL) was established from an iPSC line by introducing 3 inducible genes-c-MYC, BMI1, and BCL-XL-and subsequently generating master and working cell banks. Using the working cell bank and turbulent flow bioreactors, an allogeneic iPSC-PLT product, MEG-002, was successfully produced with clinically relevant quality and yield. MEG-002 underwent comprehensive structural and functional characterization, including in vivo efficacy testing in rabbit models, which confirmed its functionality. Preclinical safety studies revealed no concerns. A clinical trial was conducted in accordance with ethical and regulatory standards in Japan. MEG-002 was infused into a patient with aplastic anemia at a dose of 6 × 1010 platelets. No adverse events were reported, and no clinically significant changes were observed in any assessments. Furthermore, a transient increase in platelet count and evidence of iPSC-PLT circulation were observed. Despite being descriptive observations from a single subject, these findings suggest the safety and potential efficacy of allogeneic iPSC-PLTs in humans. The clinical trial is registered with the Japan Registry of Clinical Trials (jRCT2053210068).</p>","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":"15 8","pages":""},"PeriodicalIF":5.9,"publicationDate":"2026-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13446221/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148685881","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":"Five-year follow-up of phase II trial of autologous cord blood mononuclear cells for bronchopulmonary dysplasia prevention in very preterm infants.","authors":"Zhuxiao Ren, Jiangxue Han, Qi Zhang, Wei Wei, Yongsheng Li, Shumei Yang, Fang Xu, Chuan Nie","doi":"10.1093/stcltm/szag045","DOIUrl":"10.1093/stcltm/szag045","url":null,"abstract":"<p><strong>Background: </strong>We previously performed a phase II clinical trial involving the intravenous infusion of autologous cord blood mononuclear cells (ACBMNCs) to prevent bronchopulmonary dysplasia in premature infants. We reported the outcomes before discharge and at 2-year follow-up of the enrolled infants. We have reported the developmental outcomes at the 5-year follow-up visit.</p><p><strong>Methods: </strong>We evaluated the 5-year long-term outcomes of ACBMNCs infusion, including growth, respiratory, and neurodevelopmental outcomes, by interviewing the parents. Children's development was assessed using scores on the Chinese version of the Ages & Stages Questionnaires (ASQ), third edition (ASQ-3), completed by the parents or guardians. The primary outcome was the neurodevelopmental outcome. The secondary outcomes were growth and respiratory outcomes.</p><p><strong>Results: </strong>In terms of the primary endpoint, intravenously infused ACBMNCs significantly improved the scores of the fine motor and personal-social domains in the ASQ (P = .044 and P = .048, respectively). This study also showed high consistency between the motor index in the Bayley score at a 2-year follow-up with both gross and fine motor domain scores, as well as the language index with communication, problem-solving, and personal-social domain scores. Although pneumonia-related hospitalizations were similar between the two groups, the intervention group showed a lower possibility of nocturnal cough.</p><p><strong>Conclusion: </strong>Infants who received intravenous ACBMNC infusion had better fine motor and personal-social abilities at 5 years than those in the control group. In addition to providing reassuring safety data, the study suggested longer-term neurodevelopmental benefits of ACBMNC intervention early in the NICU course. Further randomized placebo-controlled trials are essential to confirm these findings.</p><p><strong>Trial registration: </strong>The trial was prospectively registered at ClinicalTrials.gov (NCT02999373), registered on December 21, 2016.</p>","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":"15 8","pages":""},"PeriodicalIF":5.9,"publicationDate":"2026-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13415465/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148607571","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":"Differential miRNA profiles in fluoride-exposed rBMSCs-EVs and the influence of miR-320-3p transfer on osteogenic differentiation.","authors":"Mingyue Yin, Jing Zhang, Na Wang, Peng Luo, Xueli Pan","doi":"10.1093/stcltm/szag064","DOIUrl":"10.1093/stcltm/szag064","url":null,"abstract":"<p><p>Long-term excessive fluoride ingestion may lead to skeletal fluorosis, a disease characterized by unclear pathogenesis and lack of effective cure. Bone marrow mesenchymal stem cell-derived extracellular vesicles (BMSCs-EVs) exert a crucial regulatory effect on bone remodeling and have broad clinical application prospects. Whether BMSCs-EVs can participate in the occurrence and development of skeletal fluorosis by transferring miRNAs is a scientific question worth exploring. In this study, miRNA sequencing was used to screen for differentially expressed miRNAs in fluoride-exposed rBMSCs-EVs (F-EVs). The top 15 differentially expressed miRNAs were subjected to target gene prediction, and GO and KEGG analyses as well as PPI network construction were performed. On this basis, miR-320-3p was selected for in-depth study. First, our data revealed that miR-320-3p was upregulated in fluoride-exposed osteoblasts and was involved in the enhancement of fluoride-induced osteogenic differentiation. Subsequently, a tracing experiment confirmed that rBMSCs-EVs and their miR-320-3p could be successfully taken up by fluoride-exposed osteoblasts. Then, elevated levels of miR-320-3p in F-EVs could further promote the enhancement of fluoride-induced osteogenic differentiation, while EVs with inhibited miR-320-3p exerted a significant inhibitory effect. Mechanism studies revealed that under fluoride exposure, rBMSCs-EVs could regulate Igf1r/ERK1/2/MAPK by transferring miR-320-3p, thereby affecting osteogenic differentiation. This study is the first to elucidate the pathogenesis of skeletal fluorosis from the rBMSCs-EVs miRNAs and provides new ideas for the clinical management of skeletal fluorosis.</p>","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":"15 8","pages":""},"PeriodicalIF":5.9,"publicationDate":"2026-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13441180/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148679832","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}