STEM CELLS最新文献

{"title":"A novel trained mesenchymal stromal cell-based therapy, HXB-319, effectively controls progressive glomerulonephritis in a murine lupus model.","authors":"Hulya Bukulmez, Adrienne Dennis, Jane Reese, Sarah Kleinsorge-Block, Scott Sieg, Kristin B Highland, Steven N Emancipator","doi":"10.1093/stmcls/sxaf040","DOIUrl":"https://doi.org/10.1093/stmcls/sxaf040","url":null,"abstract":"<p><strong>Introduction: </strong>Systemic lupus erythematosus (SLE) is driven by abnormal type-I and -II interferon activation, affecting a variety of immunocompetent cells. Mesenchymal stromal cells (MSCs) can modulate inflammation but often lack consistent potency. We developed HXB-319, an MSC-based therapy targeting inflammatory pathways in SLE. Previously, HXB-319 was shown to reduce alveolar hemorrhage in an SLE model. Here, we report its effects in a model of SLE that progresses to end stage kidney disease.</p><p><strong>Materials and methods: </strong>SLE-like disease was induced via intraperitoneal (IP) pristane injection in female BALB/cJ mice, followed by treatment with naïve MSCs or HXB-319. Over 9 months, survival and proteinuria were monitored. Upon euthanasia, kidneys were analyzed for histopathology and gene expression, splenocytes for immune subsets by flow cytometry, and serum for autoantibodies, growth factors and cytokines.</p><p><strong>Results: </strong>HXB-319 significantly altered plasmacytoid dendritic cells, CD4+PD-L1+ cells and both CD4+ and CD8+ RORγt+ (Th17 cells) subsets. HXB-310 lowered IFN-γ (p< 0.001), IL-17A (p=0.01), BAFF (p<0.05), and anti-dsDNA (p<0.05), compared to untreated mice. HXB-319, but not naïve MSCs, significantly improved survival, halted progression of kidney disease and stabilized proteinuria (all p < 0.05).</p><p><strong>Conclusion: </strong>HXB-319 demonstrates potential for mitigating SLE associated glomerulonephritis, improving survival and reducing proteinuria and glomerulosclerosis.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144525760","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":"m6A mRNA demethylase FTO promotes chondrogenic differentiation of human bone marrow mesenchymal stem cells by targeting SMAD3.","authors":"Tao Shu, Dongfeng Zhang, Jiachun Li, Hanzhong Liu, Lukuan Cui, Juyuan Gu, Liang Wu, Wenfen Liu, Junming Wan, Xiaozuo Zheng","doi":"10.1093/stmcls/sxaf035","DOIUrl":"https://doi.org/10.1093/stmcls/sxaf035","url":null,"abstract":"<p><p>Bone marrow mesenchymal stem cells (BMSCs) have chondrogenic differentiation potential to treat cartilage injury. N6 methyladenosine (m6A), one of the most prevalent mRNA modification, has been reported to be crucial in cartilage disease. Herein, we further investigated the effects and underlying mechanisms in the modification of m6A on the chondrogenic differentiation of MSCs. This study showed that the m6A level was decreased in the chondrogenic differentiation of MSCs and m6A mRNA demethylation fat mass and obesity-associated protein (FTO) played an important role in these processes. The overexpression of FTO has been demonstrated to improve the levels of chondrogenic markers. We confirmed that FTO directly binded to SMAD3 mRNA and increased its demethylation, which promoted the chondrogenic differentiation of MSCs. We further indicated that the m6A \"reader\" YTHDF2 was probably related with the chondrogenic differentiation of MSCs. SiFTO attenuated the SiYTHDF2-increased mRNA stability of SMAD3, leading to the declining levels of chondrogenic markers. Collectively, these results reveal FTO could act as an important mediator of SMAD3 mRNA demethylation and improve the chondrogenic differentiation of MSCs.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144504332","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":"Correction to: Importin 13 Serves as a Potential Marker for Corneal Epithelial Progenitor Cells.","authors":"","doi":"10.1093/stmcls/sxaf037","DOIUrl":"10.1093/stmcls/sxaf037","url":null,"abstract":"","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":"43 7","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144473574","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":"In reply to Letter to the Editor from Paudel: Comment on \"Changes in iPSC-Astrocyte Morphology Reflect Alzheimer's Disease Patient Clinical Markers\".","authors":"Noel J Buckley, Helen A Rowland","doi":"10.1093/stmcls/sxaf031","DOIUrl":"10.1093/stmcls/sxaf031","url":null,"abstract":"","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/PMC12202090/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144075012","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":"Transcriptomic analysis of the m6A reader YTHDF2 in the maintenance and differentiation of human embryonic stem cells.","authors":"Boshi Feng, Yanxi Chen, Huanchang Tu, Jin Zhang, Lingling Tong, Xiaohan Lyu, Aaron Trent Irving, Di Chen","doi":"10.1093/stmcls/sxaf032","DOIUrl":"10.1093/stmcls/sxaf032","url":null,"abstract":"<p><p>As the most abundant internal modification on mRNAs, N6-methyladenosine (m6A) has been discovered to be involved in different biological processes. Mostly determined by m6A methyl-transferases (m6A writers) and demethylases (m6A erasers), different cell types possess differential m6A profiles of transcriptomes. However, the interpretation of the m6A-encoded epitranscriptomic information needs m6A readers to bind and recruit different machinery for regulating the target mRNAs, which in turn, may regulate cell fates. The functions of the m6A readers in the regulation of the maintenance and differentiation of human embryonic stem cells (hESCs) remain largely unknown. In this study, we deleted the whole genomic region of the m6A reader YTHDF2 and discovered that YTHDF2 is dispensable for the maintenance, but important for the differentiation of hESCs, especially for the differentiation towards ectoderm. Furthermore, we identified the m6A-modified ROBO1 mRNAs as potential targets by YTHDF2 in regulating hESC to neuroectoderm differentiation. This study reveals the potential roles of the m6A reader YTHDF2 in regulating the specification of neuroectodermal cell fate.</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/PMC12202760/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144148896","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":"Comment on \"Changes in iPSC-Astrocyte Morphology Reflect Alzheimer's Disease Patient Clinical Markers\".","authors":"Leepy Paudel","doi":"10.1093/stmcls/sxaf030","DOIUrl":"10.1093/stmcls/sxaf030","url":null,"abstract":"","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/PMC12202085/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143954445","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":"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}

{"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}

{"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}

{"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}