Stem Cell Research & Therapy最新文献

{"title":"PDLSC-CM targets HAPLN1 in macrophages to reduce root resorption in delayed replanted teeth.","authors":"Lu Jia, Zengbo Zhao, Ying Zhang, Liping Zhang, Yan Liu, Hongyu Ma, Peng Zhang, Xiangdong Liu, Lu Zhang, Hang Yang, Zihan Yang, Zhe Ma, Huimin Wang, Zhiyong Hou, Huijie Ma","doi":"10.1186/s13287-026-05154-7","DOIUrl":"10.1186/s13287-026-05154-7","url":null,"abstract":"<p><strong>Background: </strong>Tooth avulsion is the most serious dental trauma, mainly affecting anterior teeth in adolescents. Delayed tooth replantation is the most common situation in clinical, but root resorption is a common complication that can lead to tooth loss. As implant is not feasible in adolescents, strategies to mitigate root resorption remain a major challenge in dentistry. We aim to evaluate the therapeutic effect and potential target of periodontal ligament stem cell-conditioned medium (PDLSC-CM) to reduce root resorption in delayed replanted tooth.</p><p><strong>Methods: </strong>Clinical samples from delayed tooth replantation patients were analyzed by X-ray and histological staining. A rat model of delayed tooth replantation was established, with PDLSC-CM applied as the tooth preservative and irrigating solution. Root resorption was assessed by micro-CT and histopathology. Proteomic screening followed by Western blot and immunofluorescence was used to identify and validate key molecules. Macrophage polarization and osteoclastogenesis were examined in vitro using RAW264.7 and bone marrow-derived macrophages. Recombinant adeno-associated virus (rAAV) was used to validate the key protein molecules.</p><p><strong>Results: </strong>Human avulsed tooth with delayed replantation shows obvious root resorption and high expressions of inflammatory cytokines and osteoclast-related factors in periapical tissue. PDLSC-CM reduces the root resorption and inhibits the expressions of inflammatory cytokines and osteoclast-related factors in root and periapical tissue of delayed replantation of avulsed tooth in rats. PDLSC-CM downregulates the expression of HAPLN1 mainly in macrophages, thereby inhibits inflammation and osteoclastogenesis of delayed replanted tooth root. Overexpression of HAPLN1 abolishes the protective effect of PDLSC-CM on delayed replanted tooth root.</p><p><strong>Conclusion: </strong>HAPLN1 reduction in macrophages plays a pivotal role in PDLSC-CM reducing root resorption. PDLSC-CM is a promising preservation medium for avulsed teeth with potential clinical applications, and the development of drug candidate targeting HAPLN1 has favorable clinical prospects.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13599259/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148376945","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 monolayer to organoids and multi-organ microphysiological systems: advancing regenerative medicine and precision therapies.","authors":"Mahmood S Choudhery, Ahmad Niaz, Taqdees Arif, Ruhma Mahmood","doi":"10.1186/s13287-026-05111-4","DOIUrl":"10.1186/s13287-026-05111-4","url":null,"abstract":"<p><strong>Background: </strong>The landscape of in vitro models has evolved from simple two dimensional (2D) cultures to three-dimensional (3D) organoids and multi-organ microphysiological systems. Early monolayer cultures enabled directed differentiation but provided limited physiological relevance.</p><p><strong>Main body: </strong>The development of organoid technology is a significant invention, which allows the cells to self-organize into complex 3D structures to recapitulate the cell diversity, architecture and functions of natural tissues. This has enabled more effective modelling of patient-specific diseases and processes. The latest development of the multi-organ microphysiological systems, integrates organoids or engineered tissues with microfluidic channels through which nutrients are perfused, and blood flow as well as mechanical stimuli are mimicked. This technology provides precise control over the tissue microenvironment to facilitate dynamic cell interactions and communication among different tissue types.</p><p><strong>Conclusion: </strong>These platforms more precisely mimic human biological processes, thereby improving disease modelling, drug screening, and the development of tissue grafts for regenerative therapies. This review discusses the evolution from 2D monolayer cell cultures, through the formation of organoids, to the engineering of organ-on-a-chip systems. It underlines how these technologies have advanced regenerative therapies by enhancing the ability to repair or replace damaged tissues and precision medicine through the creation of patient-specific disease models and personalized treatment strategies. Importantly, this review provides a comparative critical assessment of the functional capabilities, limitations, and translational readiness of each platform, identifying the specific contexts in which each system excels or falls short of its alternatives.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13599119/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148370028","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":"SATB1 regulates the osteogenic differentiation of PDLSCs via HDAC1 mediated non-histone protein deacetylation and ubiquitination mechanism and through p38 MAPK pathway under hydrogen peroxide-induced senescent conditions.","authors":"Meijun Hu, Jiaxin Song, Wanhao Yan, Yu Jiang, Chen Zhang, Haoqing Yang, Zhipeng Fan","doi":"10.1186/s13287-026-05150-x","DOIUrl":"10.1186/s13287-026-05150-x","url":null,"abstract":"<p><strong>Background: </strong>Periodontitis is a chronic inflammatory disease that affects the supporting tissues around teeth. A reduction in the pluripotency of periodontal ligament stem cells (PDLSCs) has been identified as a pivotal factor in age-related alveolar bone loss. This study investigated the effects of special AT-rich binding protein 1 (SATB1) on the osteogenic differentiation capacity of PDLSCs under H₂O₂-induced senescent conditions and its potential mechanisms, thereby providing new insights into periodontal regeneration in patients with periodontitis.</p><p><strong>Methods: </strong>The osteogenic differentiation capacity of PDLSCs was determined by alkaline phosphatase (ALP) activity, alizarin red S (ARS) staining, and western blotting. Co-immunoprecipitation (Co-IP) was used to detect the binding of SATB1 to histone deacetylase 1 (HDAC1) and a ubiquitination assay was employed to detect the protein stability of SATB1.</p><p><strong>Results: </strong>Under normal and H₂O₂-stimulation conditions, SATB1 enhances osteogenic differentiation of PDLSCs by activating the p38 mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinase (ERK) signaling pathways. The Co-IP results indicated that SATB1 could physically bind to HDAC1 and the binding of SATB1 and HDAC1 proteins decreased under H₂O₂-induced senescent conditions. In addition, HDAC1 promoted the expression of SATB1 and rescued the osteogenic differentiation capacity of PDLSCs via the activation of the p38 MAPK pathway under senescent conditions. Nevertheless, HDAC1 deacetylation mutant (HDAC1-H141A-MUT) did not affect the binding of SATB1 and HDAC1 but lost the effect of upregulating the expression of SATB1. Moreover, HDAC1-H141A-MUT lost the ability to promote the osteogenic differentiation of PDLSCs and the activation of the p38 MAPK signaling pathway. Furthermore, protein half-life experiments indicated that HDAC1 hindered the degradation of the SATB1 protein, whereas HDAC1-H141A-MUT lost this function. In the end, ubiquitination assay demonstrated that HDAC1 inhibited the ubiquitination of SATB1, while HDAC1-H141A-MUT has no effect on the ubiquitination of SATB1 protein.</p><p><strong>Conclusions: </strong>SATB1 modulated the osteogenic differentiation of PDLSCs through HDAC1 mediated non-histone protein deacetylation and ubiquitination and through the p38 MAPK pathway under H₂O₂-induced senescence conditions. Therefore, this new mechanism provides a feasible strategy for promoting periodontal tissue regeneration.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13595774/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148370014","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 stem cells-conditioned medium (ADMSCs-CM) improves testicular function and sperm DNA damage via Nrf2 antioxidant signaling pathways in rat unilateral varicocele.","authors":"Somayeh Khosravi-Farsani, Farnaz Khadivi, Masoud Rafiei, Reza Ahmadi, Reza Khosravi-Farsani, Hossein Amini-Khoei, Forouzan Rahmani","doi":"10.1186/s13287-026-05145-8","DOIUrl":"10.1186/s13287-026-05145-8","url":null,"abstract":"<p><strong>Background: </strong>Varicocele is an excessive dilation of the pampiniform plexus. Although the accurate mechanism of varicocele-induced infertility is still unknown, oxidative stress plays a major function. A great attention has recently been attracted towards the MSCs' secreted factors for the treatment of diseases. So, we investigated the effect of adipose derived stem cells-conditioned medium (ADMSCs- CM) on Nrf2 signaling pathway, downstream antioxidant enzymes, sperm DNA and acrosome damage following varicocele surgery.</p><p><strong>Methods: </strong>Rats were divided into sham, varicocele, Varicocele + DMEM/F-12, and ADMSCs-CM groups. ADMSCs were isolated, confirmed, and ADMSCs-CM was prepared. Spermatogenesis quantification was done by H& E-stained testicular sections. The percentage of sperm DNA fragmentation and acrosome integrity was assessed through acridine orange and coomassie blue stainings. The testicular levels of MDA, TAC, SOD, and CAT were assessed. Relative expression of Nrf2/ Ho-1 genes evaluated through Real-time PCR.</p><p><strong>Results: </strong>Mean percentage of sperm acrosome integrity, TDI, SPI, and Johnsen's criteria decreased (p < 0.0001), mean percentage of sperm DNA fragmentation (p < 0.0001), and testicular MDA (p < 0.001) significantly increased in the varicocele group. Unilateral varicocele reduced notably testicular levels of TAC (p < 0.0001), SOD (p < 0.01), and CAT (p < 0.05). ADMSCs-CM improved significantly sperm acrosome integrity (p < 0.01) and sperm DNA fragmentation (p < 0.05). Also, results demonstrated a remarkable recovery in spermatogenic parameters. There is a significant improvement in MDA, SOD (p < 0.05), and TAC (p < 0.01) levels in the ADMSCs-CM group. Treatment with AMSCs resulted in a non-significant increase in the mRNA expression of both Nrf2 and Ho-1 genes compared with the varicocele group, whereas a significant increase was observed compared with the sham group.</p><p><strong>Conclusions: </strong>Intratesticular administration of ADMSCs-CM could be a promising approach for the partial restoration of spermatogenesis and sperm damage potentially through Nrf2 antioxidant signaling pathway and reducing oxidative injury induced by varicocele.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13599101/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148377020","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":"Emerging roles of the long non-coding RNAs MALAT1 and TUG1 during differentiation of adipose tissue-derived mesenchymal stem cells towards insulin-producing cells.","authors":"Eman F Sanad, Alaa Ahmed Saad, Joy Rafeek, Rana Mokbel, Mayar Abdallah, Nadeen Emad, Hagar Adel Mohamed, Yasmin Alaa, Yumna Medhat Mahmoud, Dina H Kassem","doi":"10.1186/s13287-026-05125-y","DOIUrl":"10.1186/s13287-026-05125-y","url":null,"abstract":"<p><strong>Background: </strong>Generation of insulin-producing cells (IPCs) from stem cells provides great hope for patients with diabetes mellitus (DM). Long non-coding RNAs (lncRNAs) ignited much interest regarding their role in determining the fate of stem cells. The lncRNAs MALAT1 and TUG1 have been reported to be interrelated with β-cell dysfunction and/or DM. However, their role during generation of IPCs from stem cells has not been adequately studied. Thus, the current study aimed to investigate the role of MALAT1 and TUG1 during differentiation of adipose tissue-derived mesenchymal stem cells (Ad-MSCs) towards IPCs.</p><p><strong>Methods: </strong>Ad-MSCs were isolated from rat epididymal fat pads, characterized and induced to differentiate towards IPCs. Assessment of differentiation was done by measuring expression levels of various β-cell-related markers using RT-qPCR, as well as morphological changes, and dithizone staining. Expression levels of MALAT1 and TUG1 were also measured by RT-qPCR. Several in-silico analyses were done using RNA-protein Association and Interaction Networks (RAIN) database.</p><p><strong>Results: </strong>MALAT1 and TUG1 expression levels were significantly increased during differentiation of Ad-MSCs into IPCs as compared to control uninduced cells. Furthermore, generated networks from RAIN database revealed an interplay between MALAT1 and TUG1, and between each of them with several common targets like GAS5, HOTAIR and TP53COR1.</p><p><strong>Conclusions: </strong>The current study portrays MALAT1 and TUG1 as novel interrelated molecular mediators and important regulatory nodes enhancing differentiation of Ad-MSCs towards IPCs. Their upregulation during differentiation can be interrelated with competitive endogenous RNA (ceRNA) networks, mediating various epigenetic modifications, orchestrating signaling pathways and overcoming cellular stress during reprogramming/differentiation.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"17 1","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13325589/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148368958","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":"FGFR1 frameshift mutation mediates the dysfunction of mesenchymal stem cells in craniofacial microsomia.","authors":"Shanbaga Zhao, Pan Luo, Chen Ke, Lei Li, Zhifeng Li, Bingyang Liu, Lunkun Ma, Tianying Zang, Hongwen Li, Xi Xu, Tian He, Bincheng Wang, Xiaojun Tang","doi":"10.1186/s13287-026-05096-0","DOIUrl":"10.1186/s13287-026-05096-0","url":null,"abstract":"<p><p>Craniofacial microsomia represents a congenital craniofacial anomaly characterized by a complex etiology, the precise genetic determinants of CFM have remained largely elusive. Comprehensive exome sequencing analysis performed on a cohort of CFM patients has identified a specific pathogenic frameshift mutation (c.225dupA, p. I76fs) located within the Fibroblast Growth Factor Receptor 1 gene. Extensive functional characterization utilizing human umbilical cord-derived mesenchymal stem cells demonstrated that either the presence of this FGFR1 mutation or the targeted knockdown of FGFR1 significantly attenuated the endogenous expression of the receptor. This genetic perturbation was associated with a marked impairment of osteogenic differentiation potential, a substantial reduction in cellular proliferative and migratory capacities, and an exacerbated apoptotic response. From a mechanistic perspective, the disruption of FGFR1 function exerted a suppressive effect on pivotal signaling cascades essential for skeletal development, including the P38/ERK, Wnt/β-catenin, BMP2/SMAD4, and PI3K/AKT transduction axes. Furthermore, the integrity of critical molecular interactions between FGFR1 and structural co-factors, specifically vimentin, COL1A1, and FGF1, was compromised, resulting in a concomitant downregulation of their protein abundance. Collectively, these findings elucidate that the FGFR1 frameshift mutation is a significant contributor to the pathogenesis of CFM, principally by obstructing MSC-mediated osteogenesis through the dual disruption of essential signal transduction pathways and vital protein-protein interaction networks.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13587315/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148362497","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":"Orthodontic loading modulates epithelial progenitor dynamics and enamel formation in the mouse mandibular incisor.","authors":"Idan Bar On, Yehuda Klein, Elias Shahin, Jihan Asmar, Sanako Takano, Jimmy K Hu, Stella Chaushu, Amnon Sharir","doi":"10.1186/s13287-026-05138-7","DOIUrl":"10.1186/s13287-026-05138-7","url":null,"abstract":"<p><strong>Background: </strong>Adult stem cells (SCs) maintain tissue homeostasis through a balance of self-renewal and differentiation regulated by biochemical and mechanical cues. While biochemical pathways are well studied, the in vivo mechanisms by which external forces influence SCs and their progeny remain poorly understood. The continuously growing mouse incisor offers a tractable model for investigating these mechanisms because dental epithelial stem cells (DESCs) reside in a spatially restricted apical niche, and their progeny undergo stereotyped proliferation and differentiation along the apical-incisal axis. We investigated how intrusive mechanical loading affects dental epithelial cell kinetics and enamel regeneration during injury repair.</p><p><strong>Methods: </strong>A modified orthodontic tooth movement device was adapted to apply controlled intrusive forces (0.05-0.5 N) to the mouse mandibular incisor. To stimulate regeneration, the incisal tip was trimmed, and mice were subjected to force application for three days, followed by recovery after device removal. Dental epithelial responses were evaluated using histology, dual EdU/BrdU labeling, in situ hybridization, and micro-computed tomography. Expression of proliferation (Ccnb1) and differentiation (Igfbpl1) markers, as well as nuclear localization of the mechano-responsive transcription co-factor YAP, were analyzed.</p><p><strong>Results: </strong>Forces ≥ 0.2 N caused adverse health effects, whereas 0.05 N induced consistent epithelial changes without systemic consequences. At 0.05 N loading, incisors showed delayed regeneration and hypomineralized enamel. The apical epithelium exhibited folds, tears, reduced proliferation, and premature amelogenin expression. These effects reversed after load removal, coinciding with restored proliferation and enamel deposition. Gene expression analysis revealed apical-incisal shifts in Ccnb1 and Igfbpl1 domains, consistent with altered cell kinetics. Mechanistically, loading decreased nuclear YAP localization in the central body of the labial cervical loop, suggesting a role for this mechanosensitive pathway in mediating the cellular response to mechanical force.</p><p><strong>Conclusions: </strong>This study presents an in vivo model for examining mechanical influences on dental epithelial progenitor cells. Intrusive loading suppresses proliferation, promotes precocious differentiation, and alters epithelial architecture. These findings support a role for mechanical cues in modulating tissue regeneration and provide a framework for future mechanistic studies in tooth biology.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13587434/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148362495","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":"Intratympanic injection of human umbilical cord mesenchymal stem cell derived small extracellular vesicles for refractory sudden sensorineural hearing loss: a Phase 1 trial.","authors":"Fan Shu, Yahui Wu, Yifan Zhang, Muqing Xu, Tuanming Zou, Shanshan Jiang, Jieqing Cai, Jinwei Bao, Anning Chen, Hongzheng Zhang","doi":"10.1186/s13287-026-05136-9","DOIUrl":"10.1186/s13287-026-05136-9","url":null,"abstract":"<p><strong>Background: </strong>Refractory sudden sensorineural hearing loss (RSSNHL) remains a therapeutic challenge with limited effective treatment options. Human umbilical cord mesenchymal stem cell-derived small extracellular vesicles (hucMSC-sEVs) have demonstrated otoprotective and regenerative potential in preclinical studies. This Phase 1 trial evaluated the safety of intratympanic hucMSC-sEVs in patients with RSSNHL.</p><p><strong>Methods: </strong>This single-center, open-label, single-arm clinical study enrolled RSSNHL patients between June and September 2025 (ChiCTR2500103765). Participants received intratympanic hucMSC-sEVs for five consecutive days across four dose cohorts, ranging from 8 × 10⁸ to 1 × 10¹¹ particles/mL. Follow-up assessments were conducted at 1, 2, 4, and 8 weeks after treatment, during which adverse events (AEs) were recorded, and hearing outcomes were evaluated.</p><p><strong>Results: </strong>Twelve of the thirteen enrolled patients completed the 8-week follow-up. Intratympanic administration of hucMSC-sEVs was well tolerated across all dose levels, with no dose-limited toxicity or serious AEs. The most common AEs were ear pain (5/12), ear fullness (3/12), and transient dizziness (2/12), all characteristic of intratympanic injection and resolving without intervention.</p><p><strong>Conclusions: </strong>In this Phase 1 study, intratympanic hucMSC-sEVs were well tolerated and showed preliminary signals of hearing improvement. Responses were observed only in patients receiving lower dose levels (8 × 10⁸ and 4 × 10⁹ particles/mL) and in those treated within a shorter disease window (≤ 22 days). These exploratory findings require confirmation in larger controlled trials. Trial Registration This study was registered on June 5,2025, at Chinese Clinical Trial Registry (ChiCTR2500103765).</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13587386/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148362421","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":"Correction: Essential role of p21^Waf1/Cip1 in the modulation of post-traumatic hippocampal Neural Stem Cells response.","authors":"Francesco Chiani, Valentina Mastrorilli, Nicole Marchetti, Andrea Macioce, Chiara Nappi, Georgios Strimpakos, Miriam Pasquini, Alessia Gambadoro, Jonathan Isacco Battistini, Debora Cutuli, Laura Petrosini, Sara Marinelli, Raffaella Scardigli, Stefano Farioli Vecchioli","doi":"10.1186/s13287-026-05142-x","DOIUrl":"10.1186/s13287-026-05142-x","url":null,"abstract":"","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"17 1","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13317322/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148353530","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 stem cells derived extracellular vesicles alleviate retinal excitotoxicity via miR-23a-5p/PLCD1/PKCA/GluA2 axis: a potential therapeutic strategy.","authors":"Duan Tianqi, Xu Huizhuo, Tang Shibo, Yu Haiyang, Luo Aixiang, Li Ming, Huang Jufang","doi":"10.1186/s13287-026-05140-z","DOIUrl":"10.1186/s13287-026-05140-z","url":null,"abstract":"<p><strong>Background: </strong>Despite excitotoxicity being a pivotal pathological mechanism in various retinal diseases, effective clinical interventions remain limited. Previous study has shown that adipose stem cell-derived extracellular vesicles (ADSC-EVs) can alleviate glutamate-induced retinal ganglion cells (RGCs) death by suppressing protein kinase C alpha (PKCA) pathway and increasing the expression of α-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid receptors (AMPARs) subunit 2 (GluA2) on the cell membrane, but the mechanisms remain unexplored.</p><p><strong>Methods: </strong>To clarify the molecular processes involved in ADSC-EVs-mediated intracellular calcium balance, we isolated ADSC-EVs using ultrafiltration and ultracentrifugation, and characterized these vesicles by transmission electron microscopy, nanoparticle tracking analysis, and flow cytometry. Small RNA sequencing was performed on glutamate-injured rat retinal precursor (R28) cells pre-treated with ADSC-EVs or PBS. Through bioinformatic analysis, we identified candidate microRNAs and predicted their potential target genes. The regulatory effects of microRNA were confirmed using propidium iodide staining, Fluo-4AM staining, western blotting, and immunofluorescence. Additionally, the RGCs counting and visual function tests were employed to evaluate the therapeutic efficacy of the microRNA in the glutamate-induced SD rat - animal model.</p><p><strong>Results: </strong>Our results demonstrated that pre-treatment with ADSC-EVs led to a significant increase in the expression levels of miR-127-3p, miR-181b-1-3p, miR-199a-3p/5p, miR-23a-5p, miR-23b-5p, and miR-486 in R28 cells. Bioinformatic analyses suggest that miR-23a-5p may contribute to regulating the calcium overload by inhibiting the expression of phospholipase C delta 1 (PLCD1). Overexpression of miR-23a-5p or pre-treatment with ADSC-EVs modulated the expression of GluA2 on the cell membrane through inhibiting the PLCD1/PKCA/GluA2 axis, thereby reducing intracellular calcium levels and diminishing R28 cell death. In contrast, inhibition of miR-23a-5p expression partially reversed the regulatory effects of ADSC-EVs on calcium concentration and cell viability. Furthermore, our findings suggest that overexpression of miR-23a-5p in retina alleviated glutamate-induced RGCs death and visual function impairment, whereas suppression of miR-23a-5p exacerbated glutamate-induced RGCs death.</p><p><strong>Conclusion: </strong>ADSC-EVs delived miR-23a-5p mitigate glutamate-induced RGCs damage by inhibiting the PLCD1/PKCA/GluA2 axis. Targeting this miR-23a-5p-mediated axis may therefore represent a promising therapeutic approach for excitotoxic RGCs injury.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13587503/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148362459","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}