STEM CELLSPub Date : 2025-06-24DOI: 10.1093/stmcls/sxaf028
Hsing-Yi Yu, Yang-Zhe Huang, Edward Chern
{"title":"Rabbit induced pluripotent stem cells-derived mesenchymal stem cells for enhanced wound healing.","authors":"Hsing-Yi Yu, Yang-Zhe Huang, Edward Chern","doi":"10.1093/stmcls/sxaf028","DOIUrl":"10.1093/stmcls/sxaf028","url":null,"abstract":"<p><p>Mesenchymal stem cells (MSCs) are pivotal in regenerative medicine, particularly for their efficacy in tissue repair. However, sourcing high-quality MSCs presents challenges due to limited availability and compromised function. Induced pluripotent stem cells (iPSCs) offer a promising alternative for generating MSCs through specific differentiation protocols. In this study, we employed rabbit iPSCs to explore their capacity for differentiation into MSCs, facilitated by the use of SB431542, a TGF-β signaling inhibitor. Upon treatment with SB431542, rabbit iPSCs underwent embryoid body (EB) formation, leading to successful differentiation into the mesenchymal lineage. Our results demonstrated significant upregulation of mesodermal markers while reduced expression of ectodermal and endodermal markers, confirming effective MSC differentiation. Additionally, in a mouse wound healing model, rabbit iPSC-derived MSCs significantly enhanced wound closure compared to controls. These findings highlight the potential of SB431542 in generating functional iPSC-derived MSCs, offering valuable applications in regenerative medicine across species.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144075060","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
STEM CELLSPub Date : 2025-06-24DOI: 10.1093/stmcls/sxae063
Peng Huang, Xiaofei Qin, Chuiqin Fan, Huifeng Zhong, Manna Wang, Fuyi Chen, Maochuan Liao, Nanpeng Zheng, Hongwu Wang, Bingchun Lin, Lian Ma
{"title":"Advantages of cell proliferation and immune regulation in CD146+NESTIN+ HUMSCs: insights from single-cell RNA sequencing.","authors":"Peng Huang, Xiaofei Qin, Chuiqin Fan, Huifeng Zhong, Manna Wang, Fuyi Chen, Maochuan Liao, Nanpeng Zheng, Hongwu Wang, Bingchun Lin, Lian Ma","doi":"10.1093/stmcls/sxae063","DOIUrl":"10.1093/stmcls/sxae063","url":null,"abstract":"<p><p>The heterogeneity of stem cells is a significant factor inhibiting their clinical application, as different cell subpopulations may exhibit substantial differences in biological functions. We performed single-cell sequencing on human umbilical cord mesenchymal stem cells (HUMSCs) from 3 donors of different gestational ages (22 + 5, 28, and 39 weeks). We also compared the data with single-cell sequencing data from BMSCs from 2 public databases. The content of CD146+Nestin+ MSCs in preterm HUMSCs (22 + 5W: 30.2%, 28W: 25.8%) was higher than that in full-term HUMSCs (39W: 0.5%) and BMSCs (BMSC1: 0, BMSC2: 0.9%). Cell cycle analysis indicated a higher proportion of cells in the proliferative G2M phase in CD146+Nestin+ MSCs (40.8%) compared to CD146+Nestin- MSCs (20%) and CD146-Nestin- MSCs (12.5%). The degree of differentiation assessment suggested that CD146+Nestin+ MSCs exhibited lower differentiation than other cell subpopulations. Differential gene analysis revealed that CD146+Nestin+ MSCs overexpressed immune regulation-related factors. GO and KEGG enrichment analysis of modules identified by weighted gene co-expression network analysis suggested enrichment in pathways related to cellular immune regulation, antimicrobial activity, and proliferation. Immune-related gene analysis indicated that CD146+Nestin+ MSCs exhibited expression of multiple immune-related genes associated with \"antimicrobials,\" \"cytokines,\" and \"cytokine receptors.\" Gene regulatory network analysis revealed high expression of immune-related regulators RELB, GAPB1, and EHF in CD146+Nestin+ MSCs. Our study provides a single-cell atlas of preterm HUMSCs, demonstrating the expression of CD146+Nestin+ MSCs across different tissues and confirming their advantages in cellular proliferation, antimicrobial activity, immune regulation, and low differentiation at the RNA level. This contributes valuable insights for the clinical application of HUMSCs.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12199618/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142454402","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}
STEM CELLSPub Date : 2025-06-24DOI: 10.1093/stmcls/sxaf014
Maria Soltero-Rivera, Boaz Arzi, Lynda Bourebaba, Krzysztof Marycz
{"title":"Impact of pro-inflammatory cytokine preconditioning on metabolism and extracellular vesicles in feline mesenchymal stromal cells: a preliminary study.","authors":"Maria Soltero-Rivera, Boaz Arzi, Lynda Bourebaba, Krzysztof Marycz","doi":"10.1093/stmcls/sxaf014","DOIUrl":"10.1093/stmcls/sxaf014","url":null,"abstract":"<p><strong>Background: </strong>Extracellular vesicles (EVs) derived from mesenchymal stem cells have shown promise in treating inflammation. This study investigates whether preconditioning feline adipose-derived stem cells (FeASCs) with inflammatory cytokines, specifically IFN-γ and TNF-α, enhances the anti-inflammatory efficacy of MSC-derived EVs.</p><p><strong>Objective: </strong>We hypothesize that cytokine-primed FeASCs will produce EVs with improved anti-inflammatory properties and that this preconditioning will affect mitochondrial dynamics to enhance EV therapy effectiveness.</p><p><strong>Methods: </strong>FeASCs were exposed to a TNF-α/IFN-γ combination to mimic a pro-inflammatory milieu favoring ASCs' immunosuppressive phenotype. We analyzed morphological, metabolic, and immunomodulatory characteristics of native and cytokine-primed FeASCs. EVs were assessed for anti-inflammatory and mitochondrial-related markers. We also evaluated mitochondrial function and apoptosis markers in cytokine-primed cells.</p><p><strong>Results: </strong>Cytokine priming led to significant morphological changes in FeASCs, including enhanced cell projections and increased apoptosis. EVs from cytokine-primed FeASCs exhibited a heightened immunomodulatory profile, with increased expression of both pro-inflammatory and anti-inflammatory mediators. Transcriptomic analysis of these EVs revealed the upregulation of genes associated with cell proliferation, survival, and apoptosis. Mitochondrial function was impaired in cytokine-primed cells, but mitochondrial morphology remained unchanged. EVs from these cells contained higher levels of mitochondrial-related transcripts, indicating a compensatory response.</p><p><strong>Conclusions: </strong>Cytokine-primed FeASCs generate EVs with enhanced immunomodulatory potential, highlighting their therapeutic promise. However, further research is needed to validate their efficacy and safety and refine preconditioning strategies to optimize EV-based therapies for inflammatory conditions. These advancements could pave the way for broader applications in regenerative medicine.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12199603/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143762629","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}
STEM CELLSPub Date : 2025-06-24DOI: 10.1093/stmcls/sxaf017
Shanyu Ye, Yanqing Wang, Ziwei Luo, Aijun Liu, Xican Li, Jiasong Guo, Wei Zhao, Dongfeng Chen, Lin Yang, Helu Liu
{"title":"E3 ligase Trim63 promotes the chondrogenic differentiation of mesenchymal stem cells by catalyzing K27-linked cysteine ubiquitination of Myh11.","authors":"Shanyu Ye, Yanqing Wang, Ziwei Luo, Aijun Liu, Xican Li, Jiasong Guo, Wei Zhao, Dongfeng Chen, Lin Yang, Helu Liu","doi":"10.1093/stmcls/sxaf017","DOIUrl":"10.1093/stmcls/sxaf017","url":null,"abstract":"<p><p>Mesenchymal stem cells (MSCs) are multipotent stem cells that have a chondrogenic differentiation capacity. However, the molecular mechanism underlying the chondrogenic differentiation of MSCs has not been fully elucidated, which hinders further development of MSC-based cell therapies for cartilage repair in the clinic. Here, we showed that the E3 ubiquitin ligase Trim63 positively regulates the chondrogenic differentiation of MSCs by catalyzing the K27-linked cysteine ubiquitination of Myh11. Trim63 directly interacts with Myh11 and catalyzes K27-linked ubiquitination of cys382. Mutation of cys382 diminishes Trim63-catalyzed K27-linked ubiquitination and chondrogenic differentiation of MSCs. A deficiency in Trim63 significantly impairs the chondrogenic differentiation of MSCs. Trim63 enhances the repair of articular cartilage defects in vivo. Taken together, the results of our study demonstrated that Trim63 promotes the chondrogenic differentiation of MSCs by catalyzing K27-linked cysteine ubiquitination of Myh11, which provides an alternative therapeutic target for cartilage regeneration and repair.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143956961","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
STEM CELLSPub Date : 2025-06-20DOI: 10.1093/stmcls/sxaf038
Sophie E Givens, Abygail A Andebrhan, Eric G Schmuck, Aimee Renaud, An Xie, Somayeh Ebrahimi-Barough, Juan E Abrahante, Noah Stanis, Samuel Dudley, James R Dutton, Brenda M Ogle
{"title":"Healthy human induced pluripotent stem cell-derived cardiomyocytes exhibit sex dimorphism even without the addition of hormones.","authors":"Sophie E Givens, Abygail A Andebrhan, Eric G Schmuck, Aimee Renaud, An Xie, Somayeh Ebrahimi-Barough, Juan E Abrahante, Noah Stanis, Samuel Dudley, James R Dutton, Brenda M Ogle","doi":"10.1093/stmcls/sxaf038","DOIUrl":"https://doi.org/10.1093/stmcls/sxaf038","url":null,"abstract":"<p><p>Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) are a valuable cell type for studying human cardiac health and disease in vitro. However, it is not known whether hiPSC-CM display sex dimorphism and therefore whether sex should be incorporated as a biological variable in in vitro studies that include this cell type. To date, the vast majority of studies that utilize hiPSC-CM do not include both male and female sex nor stratify results based on sex because it is challenging to amass such a cohort of cells. Here we generated three female and three male hiPSC-lines from adult left ventricular cardiac fibroblasts as a resource for studying sex differences in in vitro cardiac models. We used this resource to generate hiPSC-CM and maintained them in basal media without exogenous hormones. Functional assessment of CM showed enhanced calcium handling in female-derived hiPSC-CM relative to male. Bulk RNA sequencing revealed over 300 differentially expressed genes (DEG) between male and female hiPSC-CM. Gene ontology analysis of DEG showed distinct differences in pathways related to cardiac pathology including cell-cell adhesion, metabolic processes, and response to ischemic stress. Differential expression of the sodium channel auxiliary unit SCN3B was found and validated through patch-clamp measurements of sodium currents showing increased peak amplitude and window current in female hiPSC-CM. These findings highlight the importance of considering sex as a variable when conducting studies to evaluate aspects of human cardiac health and disease related to cardiomyocyte function.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144511285","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
STEM CELLSPub Date : 2025-06-19DOI: 10.1093/stmcls/sxaf043
Huzefa I Husain, Manci Li, Juan E Abrahante, Natalia Calixto Mancipe, Amanda Vegoe, Yi Wen Chai, Beth Lindborg, Marc Tompkins, Brenda Ogle, Peter A Larsen, Timothy D O'Brien, Ferenc Tóth
{"title":"Consistent self-organized emergence of hyaline cartilage in hiPSC-derived multi-tissue organoids.","authors":"Huzefa I Husain, Manci Li, Juan E Abrahante, Natalia Calixto Mancipe, Amanda Vegoe, Yi Wen Chai, Beth Lindborg, Marc Tompkins, Brenda Ogle, Peter A Larsen, Timothy D O'Brien, Ferenc Tóth","doi":"10.1093/stmcls/sxaf043","DOIUrl":"https://doi.org/10.1093/stmcls/sxaf043","url":null,"abstract":"<p><p>Existing protocols for in vitro hyaline cartilage production utilizing human induced pluripotent stem cells (hiPSCs) have several challenges including a complex culturing process that uses undefined culture media, phenotypic instability, and batch-to-batch variability of the cell product. Here, our primary objective is to describe a simple, xeno- and feeder-free protocol for the generation of hyaline cartilage utilizing multi-tissue organoids (MTOs). We investigated gene regulatory networks during hiPSC-MTO differentiation using RNA sequencing and bioinformatics analyses, as well as histological and immunohistochemical methods. Interplays between BMPs and neural FGF pathways associated with the phenotypic transition of MTOs are described. Comparisons across transcriptomes revealed that the expression of chondrocyte-specific genes in MTOs correlates strongly with fetal lower-limb chondrocytes. Single-cell RNA-sequencing findings confirmed that the majority of cells belonged to the chondrogenic lineage and that they were similar across MTO batches, suggesting uniformity of the culture process. Collectively, these findings demonstrate the consistent emergence of hyaline cartilage in MTOs and the molecular pathways that govern this process, thereby establishing an accessible source of functional chondrocytes for future therapeutic evaluations.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144511284","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Single-cell analysis of heterogeneity and molecular changes in cultured corneal epithelial stem cells during serial passage.","authors":"Usanee Reinprayoon, Supaporn Khramchantuk, Natthida Kittimawikrom, Praewphan Ingrungruanglert, Sarinya Phodang, Thanakorn Jaemthaworn, Sira Sriswasdi, Nipan Israsena","doi":"10.1093/stmcls/sxaf041","DOIUrl":"https://doi.org/10.1093/stmcls/sxaf041","url":null,"abstract":"<p><p>The maintenance of corneal epithelial homeostasis relies on limbal stem cells (LSCs) located at the limbus. Although short-term cultured LSC transplantation effectively treats LSC deficiency, prolonged culture leads to stemness loss and abortive colony formation, and the mechanisms remain elusive. In this study, we employed single-cell transcriptomics to investigate LSC population dynamics and changes in gene expression during extended serial culture. Transcriptomic data from 22,708 cells revealed 19 clusters, identifying three distinct limbal progenitor populations (Progenitors 1-3) with unique transcriptional profiles and cell division kinetics. All progenitor subgroups expressed stemness-related genes such as ANLN, AURKB, and HMGB2 and were detected at all stages of the cell cycle. Notably, Progenitor3 exhibited the highest levels of genes associated with stemness and the G2/M checkpoint, including ANLN, PLK1, AURKA, HMGB2, and TOP2A, and had the largest proportion of cells in G2/M. Progenitor2 was marked by histone H1 expression, while Progenitor1 displayed distinctive cell cycle kinetics. Despite stable proportions of the three progenitor populations throughout prolonged passaging, mitochondrial gene downregulation and ribosomal gene upregulation were observed. Treatment with the small molecule RepSox partially preserved LSC maintenance in long-term culture by inhibiting the epithelial-mesenchymal transition program and modulating energy and metabolic pathways. These findings provide insights for optimizing in vitro LSC expansion for cell-based therapies.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144504333","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
STEM CELLSPub Date : 2025-06-10DOI: 10.1093/stmcls/sxaf036
Nazihah Rasiwala, Gillian I Bell, Anargyros Xenocostas, David A Hess
{"title":"Contribution of cytokeratin 19-expressing cells towards islet regeneration induced by multipotent stromal cell secreted proteins.","authors":"Nazihah Rasiwala, Gillian I Bell, Anargyros Xenocostas, David A Hess","doi":"10.1093/stmcls/sxaf036","DOIUrl":"https://doi.org/10.1093/stmcls/sxaf036","url":null,"abstract":"<p><p>Residual beta cell function has been documented in 'medalist' patients that have lived with Type 1 diabetes (T1D) for >50 years. In addition, endocrine cell neogenesis first occurs in the developing human embryo from a progenitor cells derived from pancreatic ductal epithelial structure. Thus, beta cell conversion from a dormant epithelial precursor remains a promising approach to regenerate islets during T1D. We have previously shown that intra-pancreatic (iPan) injection of Wnt pathway-stimulated conditioned media (Wnt+ CdM) generated from human bone marrow-derived multipotent stromal cells (MSC) contained islet regenerative factors that reduced hyperglycemia and recovered beta cell mass in streptozotocin-treated mice. However, the endogenous source of regenerated beta cells remains unknown. Herein, we employed cytokeratin 19 (CK19)-CreERT Rosa26-mTomato lineage-tracing mice to assess endocrine conversion of CK19+ cells during MSC CdM-induced islet regeneration. Mice iPan-injected with Wnt+ CdM demonstrated reduced blood glucose levels and improved glucose tolerance compared to mice injected with unconditioned basal media. CdM-injected mice also showed increased islet number and beta cell mass, as well as CK19+ cells within regenerating islets. The frequency of insulin+ cells that co-expressed tdTomato within dissociated pancreas samples observed via flow cytometry was 5-fold higher in Wnt+ CdM-injected mice (~5%) compared to basal media-injected controls (~1%). Collectively, in vivo lineage tracing revealed conversion of CK19+ cells to functional beta cells partially contributed to islet regeneration induced by Wnt activated MSC CdM. Future studies are required to delineate alternate cell types and mechanisms participating in islet regeneration induced by direct delivery of MSC-CdM.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144256928","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
STEM CELLSPub Date : 2025-05-27DOI: 10.1093/stmcls/sxaf010
Mathilde Colinet, Ioana Chiver, Antonela Bonafina, Gérald Masset, Daniel Almansa, Emmanuel Di Valentin, Jean-Claude Twizere, Laurent Nguyen, Ira Espuny-Camacho
{"title":"SARS-CoV2 infection triggers inflammatory conditions and astrogliosis-related gene expression in long-term human cortical organoids.","authors":"Mathilde Colinet, Ioana Chiver, Antonela Bonafina, Gérald Masset, Daniel Almansa, Emmanuel Di Valentin, Jean-Claude Twizere, Laurent Nguyen, Ira Espuny-Camacho","doi":"10.1093/stmcls/sxaf010","DOIUrl":"10.1093/stmcls/sxaf010","url":null,"abstract":"<p><p>SARS-CoV2, severe acute respiratory syndrome coronavirus 2, is frequently associated with neurological manifestations. Despite the presence of mild to severe CNS-related symptoms in a cohort of patients, there is no consensus whether the virus can infect directly brain tissue or if the symptoms in patients are a consequence of peripheral infectivity of the virus. Here, we use long-term human stem cell-derived cortical organoids to assess SARS-CoV2 infectivity of brain cells and unravel the cell-type tropism and its downstream pathological effects. Our results show consistent and reproducible low levels of SARS-CoV2 infection of astrocytes, deep projection neurons, upper callosal neurons, and inhibitory neurons in 6 months of human cortical organoids. Interestingly, astrocytes showed the highest infection rate among all infected cell populations which led to changes in their morphology and upregulation of SERPINA3, CD44, and S100A10 astrogliosis markers. Further, transcriptomic analysis revealed overall changes in expression of genes related to cell metabolism, astrogliosis and, inflammation and further, upregulation of cell survival pathways. Thus, local and minor infectivity of SARS-CoV2 in the brain may induce widespread adverse effects and lead to the resilience of dysregulated neurons and astrocytes within an inflammatory environment.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12121356/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143655708","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":"MSC-derived exosomal miR-125b-5p suppressed retinal microvascular endothelial cell ferroptosis in diabetic retinopathy.","authors":"Jun Tong, Yueqin Chen, Xinru Ling, Zhenping Huang, Genhong Yao, Zhenggao Xie","doi":"10.1093/stmcls/sxaf023","DOIUrl":"10.1093/stmcls/sxaf023","url":null,"abstract":"<p><p>Progressive endothelial cell injury of retinal vascular is a vital factor in diabetic retinopathy (DR) pathogenesis. Mesenchymal stem cells-derived small extracellular vesicles (MSC-sEVs) showed beneficial effects on DR. However, the effects of MSC-sEVs on endothelial dysfunction of DR and the mechanism is still unclear. In this study, MSC-sEVs mitigated retinal blood-retina barrier (BRB) impairment in rats with streptozotocin (STZ)-induced DR by reducing ferroptosis in vivo and in vitro. MSC-sEVs miRNA sequencing analysis revealed that miR-125b-5p may mediate human retina microvascular endothelial cells (HRMECs) ferroptosis and P53 as a downstream target based on dual-luciferase reporter assays. Silencing miR-125b-5p in MSC-sEVs reversed the therapeutic effects of MSC-sEVs on rats with DR and advanced glycation end products (AGEs)-treated HRMECs. Additionally, overexpression of miR-125b-5p could diminish ferroptosis in HRMECs, and this effect could be effectively reversed by overexpressing P53. This study indicated the potential therapeutic effect of MSC-sEVs on vascular endothelial function maintenance and that the delivery of sEVs carrying miR-125b-5p could prevent endothelial cell ferroptosis by inhibiting P53, thereby protecting the BRB.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143956900","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}