STEM CELLS最新文献

{"title":"15-PGDH inhibition enhances hematopoietic regeneration during aging.","authors":"Rahul Chaudhary, Brittany A Cordova, Marcus Hong, Bailey R Klein, Lyannah A Contreras, Ritisha Rashmil, Filip Goshevski, Julianne N P Smith, Derek J Taylor, Andrew A Pieper, Sanford Markowitz, Amar B Desai","doi":"10.1093/stmcls/sxaf047","DOIUrl":"https://doi.org/10.1093/stmcls/sxaf047","url":null,"abstract":"<p><p>Hematopoietic aging is characterized by diminished stem cell regenerative capacity and an increased risk of hematologic dysfunction. We previously identified that the prostaglandin-degrading enzyme 15-hydroxyprostaglandin dehydrogenase (15-PGDH) regulates hematopoietic stem cell activity. Here, we expand on this work and demonstrate that in aged mice, (1) 15-PGDH expression and activity remain conserved in the bone marrow and spleen, suggesting it remains a viable therapeutic target in aging, (2) prolonged PGDH inhibition (PGDHi) significantly increases the frequency and number of phenotypic hematopoietic stem and progenitor cells across multiple compartments, with transcriptional changes indicative of enhanced function, (3) PGDHi-treated bone marrow enhances short-term hematopoietic recovery following transplantation, leading to improved peripheral blood output and accelerated multilineage reconstitution, and (4) PGDHi confers a competitive advantage in primary hematopoietic transplantation while mitigating age-associated myeloid bias in secondary transplants. Notably, these effects occur without perturbing steady-state blood production, suggesting that PGDHi enhances hematopoiesis under regenerative conditions while maintaining homeostasis. Our work identifies PGDHi as a translatable intervention to rejuvenate aged HSCs and mitigate hematopoietic decline.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144558663","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":"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":"Stem Cells within the HPA Axis in Tissue Homeostasis and Disease.","authors":"Mario Schubert, Kaomei Guan, Charlotte Steenblock","doi":"10.1093/stmcls/sxaf039","DOIUrl":"https://doi.org/10.1093/stmcls/sxaf039","url":null,"abstract":"<p><p>The hypothalamus-pituitary-adrenal (HPA) axis is crucial for the energy metabolism, cardiovascular function, and stress response. Importantly, neuronal signalling circuits in the hypothalamus, along with hormones released from the pituitary and adrenal gland, must adapt to physiological demands or pathological conditions. Stem and progenitor cells are pivotal in this regulation, either by giving rise to distinct cell types or by interacting with progenitor or hormone-producing cells. While lineage-tracing studies in rodent models have explored the role of stem cells in the HPA axis, our understanding of the mechanisms underlying this dynamic tissue plasticity remains limited, especially in humans. Moreover, single-cell RNA sequencing has revealed significant heterogeneity among stem cell populations in the HPA-axis, raising questions about the functional relevance of individual subclusters during development and adulthood. In this concise review, we summarise current knowledge on stem cells in the HPA axis, focusing on their origins, localisation of different stem cell populations, and sex-specific activity in maintaining tissue integrity. We further address their role under pathophysiological conditions, including metabolic disease, cancer, and stress. Lastly, we discuss emerging strategies for replacing lost or damaged stem or progenitor cells during ageing, highlighting recent achievements in the in vitro differentiation of hypothalamic, pituitary, and adrenal stem cells.</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":"144537603","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}