STEM CELLS最新文献

{"title":"Human umbilical cord mesenchymal stem cells enhance folliculogenesis and fertility in premature ovarian failure mice via regulating steroid synthesis.","authors":"Xingyu Xu, Jiaxuan Zhang, Yi Li, Xiaoyu Wang, Tonghui Zhu, Zhaohua Zhang, Hongli Li, Xiaolei Liang","doi":"10.1093/stmcls/sxag037","DOIUrl":"10.1093/stmcls/sxag037","url":null,"abstract":"<p><strong>Background: </strong>Premature ovarian failure (POF) is a dysfunction that severely impacts women's physiological health and reproductive function. Human umbilical cord mesenchymal stem cell (hUCMSC) transplantation offers a promising therapeutic option for restoring ovarian function. However, its efficacy and underlying mechanisms are not yet fully understood.</p><p><strong>Methods: </strong>A POF mouse model was established using cyclophosphamide induction, and hUCMSCs were transplanted into the ovaries through in situ injection. Treatment efficacy was evaluated by assessing hormone levels, estrous cycle, follicle count, and reproductive outcomes. Furthermore, metabolomic sequencing was performed on the ovarian tissues of mice to explore the mechanism underlying the therapeutic effect of hUCMSCs.</p><p><strong>Results: </strong>Compared with the POF control group, the hUCMSC treatment group showed significant improvements: primordial and primary follicle counts increased by 8-fold and 5-fold, respectively, while atretic follicle ratios decreased by 50%. Pregnancy rates in treatment group increased from 30% to 60%, with average litter sizes rising from 1.6 pups/litter to 4.1 pups/litter. The expression of key genes (Cyp11a1, Cyp19a1, Star) in the steroidogenesis pathway was significantly upregulated in ovarian tissues, which restored the levels of steroid hormones such as progesterone and thereby stabilized serum sex hormone levels.</p><p><strong>Conclusions: </strong>In situ injection of hUCMSCs can restore ovarian function and fertility in POF mice by reducing granulosa cell apoptosis and upregulating steroidogenesis pathways.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148987327","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":"Editor's Note: Hyaluronan Is Crucial for Stem Cell Differentiation into Smooth Muscle Lineage.","authors":"","doi":"10.1093/stmcls/sxag055","DOIUrl":"10.1093/stmcls/sxag055","url":null,"abstract":"","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":"44 10","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13661007/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149178346","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":"EPLIN stabilizes cell-cell adhesion complexes to facilitate TGF-β1-induced fibroblastic differentiation of human periodontal ligament stem cells.","authors":"A-Hyeong Choi, Seon-Yle Ko, Young-Joo Jang","doi":"10.1093/stmcls/sxag053","DOIUrl":"10.1093/stmcls/sxag053","url":null,"abstract":"<p><strong>Objectives: </strong>Periodontal ligament stem cells (hPDLSCs) are essential for periodontal regeneration, yet the molecular mechanisms governing their differentiation into functional fibroblasts remain poorly understood. This study aimed to identify novel regulatory molecules of PDL fibroblastic differentiation and elucidate the role of epithelial protein lost in neoplasm (EPLIN) in the fibroblastic differentiation.</p><p><strong>Methods: </strong>hPDLSCs were differentiated into PDL fibroblasts using TGF-β1. A novel antibody (anti-LG45) identified EPLIN as a target antigen. Functional roles of EPLIN were investigated through siRNA-mediated depletion and ectopic overexpression. Phalloidin staining for F-actin and co-immunoprecipitation were performed to analyze adherens junction integrity.</p><p><strong>Results: </strong>TGF-β1 treatment successfully induced fibroblastic differentiation, as evidenced by significant increases in fibroblastic marker expressions, which were abolished by the TGF-β receptor inhibitor SB-431542. A novel anti-LG45 antibody was found to specifically recognize EPLIN in differentiated PDL fibroblasts. EPLIN depletion significantly reduced the fibroblastic differentiation and disrupted the typical elongated morphology of PDL fibroblasts. Mechanistically, EPLIN depletion led to filament fragmentation and cytoskeletal collapse, decoupled N-cadherin from the cytoskeleton, and accelerated cell proliferation. Conversely, ectopic overexpression of EPLIN-α or β was sufficient to inhibit proliferation and induce fibroblastic markers even without TGF-β1 stimulation.</p><p><strong>Conclusion: </strong>EPLIN is a key regulatory factor that stabilizes the linkage between the actin cytoskeleton and adherens junctions, maintaining the fibroblastic phenotype and preventing unscheduled proliferation in hPDLSCs. This study indicates the importance of cytoskeletal structural integrity in PDL differentiation. Under this circumstance, EPLIN serves as a regulator that maintains the fibroblastic differentiation state of hPDLSCs and prevents unscheduled proliferation.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13653676/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149035936","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":"Transverse tibial transport accelerated of diabetic wound healing via enhanced Wnt/β-catenin-driven BMSCs mobilization and angiogenesis.","authors":"Baoping Deng, Xiaoyong Ge, Junjie Li, Weiping Deng","doi":"10.1093/stmcls/sxag049","DOIUrl":"10.1093/stmcls/sxag049","url":null,"abstract":"<p><strong>Background: </strong>The management of severe diabetic foot ulcers (DFUs) remains a major clinical challenge. Tibial cortex transverse transport (TTT) has emerged as an effective surgical intervention, but its underlying mechanism, particularly concerning stem cell mobilization and signaling pathways, is largely unknown.</p><p><strong>Methods: </strong>A diabetic DFU model was established in New Zealand white rabbits using Streptozotocin (STZ), followed by TTT surgery. Wound healing was evaluated through photography, H&E, and Masson's trichrome staining. Angiogenesis was assessed by high-resolution X-ray angiography and immunofluorescence. Bone marrow-derived mesenchymal stem cell (BMSC) mobilization was analyzed via CFU-F assays and flow cytometry. Serum levels of SDF-1α, CXCR4, VEGF, and Ang2 were measured by enzyme-linked immunosorbent assay and quantitative real-time polymerase chain reaction. The activity of the Wnt/β-catenin pathway was determined by Western blot.</p><p><strong>Results: </strong>Tibial cortex transverse transport significantly accelerated wound closure and enhanced tissue regeneration, with improved epidermal/dermal restoration and collagen deposition. Consistently, neovascularization in wounds was markedly promoted. Mechanistically, TTT activated the Wnt/β‑catenin signaling pathway in BMSCs, which was associated with enhanced BMSC quantity, mobilization, and migration capacity. Inhibition of this pathway attenuated the TTT‑induced pro‑healing effects.</p><p><strong>Conclusion: </strong>Tibial cortex transverse transport promotes healing of DFUs primarily by activating the Wnt/β-catenin pathway in BMSCs, thereby enhancing their mobilization, homing, and pro-angiogenic capacity. This study reveals a key molecular mechanism underlying TTT's efficacy and supports its therapeutic potential for refractory Diabetic foot ulcer (DFU).</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148872290","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":"Expression of Concern: Hyaluronan Is Crucial for Stem Cell Differentiation into Smooth Muscle Lineage.","authors":"","doi":"10.1093/stmcls/sxag050","DOIUrl":"10.1093/stmcls/sxag050","url":null,"abstract":"","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":"44 10","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13613004/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149015039","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":"Mesenchymal stem cells and empagliflozin: a potential therapeutic approach for autophagy and Klotho modulation in diabetic kidney disease.","authors":"Marcella L Franco, Stephany Beyerstedt, Bruno S Barbosa, Tuany R Alves, Andrei F da Silva, Melise O Mariano, Alanah K G Carlos, Jaqueline C Arjona, Gleice R Josefi-Rocha, Rosana M C Bastos, Érika B Rangel","doi":"10.1093/stmcls/sxag043","DOIUrl":"10.1093/stmcls/sxag043","url":null,"abstract":"<p><strong>Background: </strong>Diabetic kidney disease (DKD), the leading cause of end-stage renal disease, involves injury across multiple renal compartments. Autophagy dysregulation is a key pathogenic mechanism and may reduce Klotho, a renoprotective protein diminished in DKD. This study evaluated whether bone marrow-derived mesenchymal stem cells (MSCs), combined with empagliflozin and calorie restriction, could modulate autophagy and preserve Klotho expression in DKD.</p><p><strong>Methods: </strong>Male BTBRob/ob mice, a leptin-deficient model that develops diabetes and DKD in a progressive manner, were assigned to experimental groups and euthanized at 14-15 or 18-20 weeks. Kidney tissues were analyzed by qPCR, Western blot, and immunohistochemistry.</p><p><strong>Results: </strong>MSCs therapy improved hyperglycemia in a time-dependent manner (P < .0001), decreased albuminuria, and modestly improved eGFR, though weight gain persisted. Treatment modulated LC3 protein expression in cortical and medullary regions (P < .05), suggesting attenuation of early autophagy hyperactivation. It also helped maintain Klotho expression, correlating with reduced oxidative stress (P < .05).</p><p><strong>Conclusion: </strong>Overall, MSCs combined with empagliflozin and calorie restriction show promise as a translational approach for DKD, warranting further long-term preclinical studies.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148647987","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":"Donor sex modulates hiPSC-derived cardiomyocyte metabolic and functional response to fatty acids.","authors":"Anna K McClain, Cody Callahan, Saivee S Shelke, Roni Shir, Sophie E Givens, Brenda M Ogle, Janet Zoldan","doi":"10.1093/stmcls/sxag047","DOIUrl":"10.1093/stmcls/sxag047","url":null,"abstract":"<p><strong>Background: </strong>Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) enable cardiovascular disease modeling and regenerative research but exhibit substantial heterogeneity and incomplete metabolic maturation. Palmitate (PA) and oleate (OA) can promote aerobic maturation, although responses vary. Despite sex differences in adult cardiac metabolism, sex effects in hiPSC-CMs remain poorly defined.</p><p><strong>Methods: </strong>We assessed sex-dependent metabolic and functional responses in hiPSC-CMs from three male and three female lines treated with PA or OA. Contractile function, aerobic metabolism, and transcriptomic profiles were evaluated.</p><p><strong>Results: </strong>Sex differences were modest at baseline but pronounced after FA treatment. Male- and female-derived hiPSC-CMs responded differently to PA and OA across contractile, metabolic, and transcriptional measures, indicating that FA identity and sex jointly shape hiPSC-CM phenotypes.</p><p><strong>Conclusions: </strong>Sex contributes to hiPSC-CM heterogeneity and modulates responses to FA-based maturation. Incorporating sex-specific metabolic and functional regulation may improve the consistency and physiological relevance of hiPSC-CM maturation strategies.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148786426","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":"Mitochondrial dynamics and ion channel regulation of cancer stem cells (CSCs) in metabolic flexibility and therapeutic targeting.","authors":"Krishna Samanta, Pulak Kar","doi":"10.1093/stmcls/sxag046","DOIUrl":"10.1093/stmcls/sxag046","url":null,"abstract":"<p><p>Cancer stem cells (CSCs) constitute a rare yet highly adaptable tumor subpopulation that drives tumor initiation, intratumorally heterogeneity, metastasis, recurrence, and therapy resistance. Emerging evidence indicates that mitochondrial dynamics and mitochondrial ion signaling form an interconnected regulatory network that enables CSCs to remodel their metabolic and signaling states in response to environmental and therapeutic stress. Mitochondrial architectural remodeling through fission, fusion, biogenesis, and mitophagy cooperates closely with mitochondrial Ca2+ signaling and ion transport systems, including the mitochondrial calcium uniporter (MCU), voltage-dependent anion channels (VDACs), and mitochondrial K+ channels, to regulate mitochondrial membrane potential, oxidative phosphorylation (OXPHOS), reactive oxygen species (ROS) signaling, and bioenergetic adaptation. Selected plasma membrane and ER-associated ion channels further contribute by modulating mitochondrial signaling pathways. Together, these processes govern CSC plasticity, adaptive stress tolerance, and stemness-associated programs, facilitating survival under hypoxia, nutrient deprivation, and anticancer therapy. In this review, we explore how mitochondrial dynamics and ion signaling converge to shape CSC metabolic flexibility and therapeutic resistance. We further discuss emerging diagnostic and therapeutic opportunities targeting mitochondrial dynamics-ion signaling crosstalk, while highlighting key challenges, including CSC heterogeneity, metabolic adaptability, and the need for selective strategies capable of eliminating CSCs while sparing normal stem-cell populations.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148719483","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":"Loss of ABCA4 from photoreceptor discs is associated with glial transcriptomic changes in retinal organoids.","authors":"Rossella Valenzano, Andrew McDonald, Carmen Gallego, Charlotte A Andriessen, Ioannis Moustakas, Aat A Mulder, Harald M M Mikkers, Roman I Koning, Hailiang Mei, Jan Wijnholds","doi":"10.1093/stmcls/sxag045","DOIUrl":"10.1093/stmcls/sxag045","url":null,"abstract":"<p><strong>Background: </strong>Loss-of-function mutations in the ABCA4 gene cause Stargardt disease (STGD1), the most common inherited macular dystrophy leading to progressive central vision loss.</p><p><strong>Methods: </strong>Here, we generated human induced pluripotent stem cell-derived retinal organoids harboring a premature stop codon in exon-24 of ABCA4 to evaluate the impact of this mutation on mRNA and protein levels in a human model.</p><p><strong>Results: </strong>Immunofluorescence analysis revealed the absence of ABCA4 protein in the mutant photoreceptor outer segment discs, while single-cell RNA sequencing detected no major transcriptional alterations in rods and cones. Unexpectedly, differential gene expression and pathway enrichment analyses of Müller glial cells and astrocytes highlighted disruption of neuronal development, microenvironment of glial cells, intercellular communication, and programmed cell death pathways.</p><p><strong>Conclusions: </strong>These findings suggest that ABCA4 deficiency in photoreceptor discs may trigger early stress-associated transcriptomic responses in retinal glial cells prior to overt photoreceptor degeneration, potentially contributing to Stargardt disease pathogenesis.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13529370/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148710685","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":"Engineering neural organoids: technological advances and translational frontiers.","authors":"Sungmin Kim, Hye-Ju Jo, Sung-Hwan Moon","doi":"10.1093/stmcls/sxag041","DOIUrl":"10.1093/stmcls/sxag041","url":null,"abstract":"<p><p>Neural organoids have transformed experimental neuroscience by enabling human-specific models of brain development, function, and disease. Emerging at the intersection of stem cell biology and tissue engineering, these self-organizing systems recapitulate key aspects of neurogenesis, gliogenesis, and circuit formation within a controllable in vitro context. Advances in guided patterning, vascularization, and electrophysiological monitoring have enhanced structural and functional fidelity, enabling the study of dynamic processes previously inaccessible in human models. Beyond developmental biology, neural organoids have broad translational applications, including modeling neurodevelopmental and neurodegenerative disorders, screening pharmacological compounds, and testing regenerative strategies. Integration with microfluidics, bioelectronic interfaces, and computational modeling further expands their analytical capacity, transforming organoids into modular and quantifiable platforms for mechanistic and therapeutic discovery. Despite this progress, key challenges remain, including limited maturation, inter-organoid variability, and incomplete physiological integration. Addressing these limitations requires standardized differentiation protocols, robust functional benchmarks, and cross-disciplinary collaboration. The goal is not to replicate the brain in miniature, but to reconstruct its organizing principles in an experimentally accessible system. From this perspective, neural organoids serve as a bridge between biology and technology, offering new insights into human neural complexity while advancing neuroscience and medicine.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148519694","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}