Stem Cell Reviews and Reports最新文献

{"title":"Effects Of Oxygen Tension On iPSC Morphology And Small Extracellular Vesicle Particle Characteristics.","authors":"Siti Zawiah Abdul Malik, Siti A M Imran, Min Hwei Ng, Izyan Mohd Idris, Gee Jun Tye, Jun Jie Tan, Fazlina Nordin","doi":"10.1007/s12015-026-11206-5","DOIUrl":"10.1007/s12015-026-11206-5","url":null,"abstract":"","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":"3400-3402"},"PeriodicalIF":4.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148664474","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-term Results of Allogeneic Hematopoietic Cell Transplantation (allo-HCT): Real-life Data of 15- and 20-year Survivals from a Single Center.","authors":"Kajetan Karaszewski, Jakub Góra, Monika Paluszewska, Elżbieta Urbanowska, Ewa Karakulska-Prystupiuk, Piotr Boguradzki, Agnieszka Tomaszewska, Grzegorz Władysław Basak, Wiesław Wiktor Jędrzejczak","doi":"10.1007/s12015-026-11241-2","DOIUrl":"https://doi.org/10.1007/s12015-026-11241-2","url":null,"abstract":"<p><p>Allogeneic hematopoietic cell transplantations (allo-HCT) is a procedure with long history and well-documented efficacy in treating various malignant and non-malignant diseases of the hematopoietic system. While there is a potential for late complications even over 10 years following allo-HCT, the data on longer observations are limited due to loss in follow-up, personnel and organizational changes in transplant centers, and focusing on new promising therapies instead of HCT. The study aimed to evaluate 15- and 20-year overall and progression-free survival of allo-HCT recipients in our center. During the inclusion period from 1999 to 2014, we identified 269 allo-HCT recipients. Survival analyses were performed using Kaplan-Meier curves, the Cox proportional hazards model, and the log-rank test. First, we evaluated 15- and 20-year survival rates for the entire cohort of allo-HCT recipients from matched related donor (MRD) and matched unrelated donor (MUD). Then we performed similar analyses for allo-HCT recipients due to acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), chronic myeloid leukemia (CML), myelodysplastic neoplasms (MDS), non-Hodgkin lymphomas (NHL), and severe aplastic anemia (SAA). It was confirmed that survival benefit continues also during long-term observation. Notably, the plateau effect of PFS was often observed over 20 years following allo-HCT, implying the ability to cure in a relatively large group of patients with otherwise incurable diseases.</p>","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149025886","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"hiPSC-derived Organoids and Organ-on-chip Systems: New Frontiers in Neural Tube Defect Research.","authors":"Xueyan Wang, Guandong Li, Shutong Zheng, Fengge Zhang, Miao Ren, Chenyu Xiao, Yumei Shen, Shaolin Peng, Jing Cheng, Zhonghua Yao, Hong Cheng, Jiachuan Wang","doi":"10.1007/s12015-026-11237-y","DOIUrl":"https://doi.org/10.1007/s12015-026-11237-y","url":null,"abstract":"<p><p>Neural tube defects (NTDs) result from failure of neural tube closure and remain a major cause of neonatal morbidity worldwide. Genetic, epidemiological, and animal studies have identified multiple NTD‑associated factors, but the mechanisms underlying human NTDs remain incompletely understood. Direct investigation of human NTD pathogenesis is limited by restricted access to embryonic tissues and by species differences in animal models. Conventional two‑dimensional cultures also fail to capture dynamic developmental processes such as neuroepithelial folding, tissue morphogenesis, and spatial patterning. This review synthesizes current evidence on the genetic, environmental, and morphogenetic mechanisms associated with NTDs and evaluates the applications and limitations of human organoid and organoid-on-chip models in this field. NTD‑associated genetic and environmental perturbations can produce measurable cellular and morphological phenotypes in organoid systems. These phenotypes support functional assessment of candidate pathogenic factors and mechanistic investigation. Microfluidic and bioengineering approaches further improve control over geometric boundaries, mechanical cues, and morphogen gradients, while enhancing model reproducibility. Overall, human organoid and organoid‑on‑chip platforms expand the experimental toolkit for NTD research and show potential for developmental toxicity assessment, risk‑factor screening, and patient‑specific disease modeling.</p>","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148983629","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alternative Splicing Constitutes a Transcription-independent Regulatory Layer in Replicative Senescence of Human Umbilical Cord Mesenchymal Stem Cells.","authors":"Zhen Zhang, Ning Chen, Sisi Deng, Chunqi Xu, Meirong Qin, Ping Wang","doi":"10.1007/s12015-026-11240-3","DOIUrl":"https://doi.org/10.1007/s12015-026-11240-3","url":null,"abstract":"<p><p>Mesenchymal stem cells (MSCs) inevitably undergo replicative senescence during in vitro expansion, leading to progressive loss of therapeutic efficacy. However, the global landscape of alternative splicing (AS) during this process and its relationship with transcriptional regulation remain uncharacterized. Here, we performed splicing-aware transcriptomic profiling of human umbilical cord derived MSCs across four passage points (P2, P8, P10, P12; n = 11). Using stringent AND criteria (FDR < 0.05, |ΔPSI| ≥ 0.05), we identified 112 differential splicing events (DSEs) affecting 96 genes. Skipped exon (SE) events predominated (82/112, 73.2%), with DSEs peaking at P8 (83 events), indicating that splicing reprogramming is an early senescence event. Only four genes overlapped between the 699 differentially expressed genes (DEGs) and 96 DSE genes (COL12A1, ITGA7, MYOCD, TNS3), indicating that splicing and transcriptional changes affect largely distinct gene sets. Functional enrichment revealed that DEGs converged on ECM remodeling and immune/inflammatory pathways, whereas DSE genes were significantly enriched in DNA repair pathways (Fanconi anemia, homologous recombination), and splicing factor genes showed a 5.6-fold enrichment trend among DSEs (p = 0.054). PTC-50nt rule based classification showed that in-frame changes constituted the predominant category (58.5%), with NMD_risk at only 14.6% and NMD_rescue at 26.8%. The core spliceosome component SF3B1 harbored a predicted NMD-targeting event (745 bp exon inclusion, dPSI = + 0.122), while the SR protein SRSF4 experienced a predicted NMD-rescue event (dPSI = - 0.098). Splicing factor expression profiling revealed that PTBP1 exhibited an early sharp decline at P8 (- 20.2%) followed by partial recovery, with divergent regulation of SRSF and HNRNP families. Multi-layer convergence analysis resolved the senescent MSC output into two separable molecular programs, ECM remodeling and immune modulation, driven predominantly at the transcriptional level. This study provides the first systematic characterization of the alternative splicing landscape during human MSC replicative senescence, revealing that splicing changes are largely gene-level distinct from transcriptional changes, that in-frame changes rather than NMD dominate the predicted functional consequences, and that splicing factors and DNA repair genes are preferentially affected. These findings integrate alternative splicing into the regulatory landscape of MSC senescence and establish a molecular foundation for developing splicing-aware quality control strategies in ATMP manufacturing.</p>","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148977897","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mesenchymal Stem Cell Therapy for Systemic Sclerosis: Current Evidence and Clinical Applications.","authors":"Umm E Habiba, Iqra Sarwar, David Lawrence Greene, Sabiha Shamim, Ammar Haider","doi":"10.1007/s12015-026-11236-z","DOIUrl":"https://doi.org/10.1007/s12015-026-11236-z","url":null,"abstract":"<p><p>Systemic sclerosis is a multisystem autoimmune disease characterized by immune dysfunction, vasculopathy, and progressive fibrosis, yet current therapies rarely address these pathogenic axes simultaneously. Mesenchymal stem cell therapy has gained increasing interest as a disease-modifying strategy because its therapeutic activity appears to depend largely on paracrine signaling rather than durable engraftment. Through these mechanisms, mesenchymal stem cells may suppress profibrotic fibroblast activation, recalibrate innate and adaptive immune responses, and enhance vascular repair. Cell-free approaches, particularly extracellular vesicles and exosome-based therapeutics, are further expanding the translational potential of this field by offering scalable alternatives to live cell administration. Early clinical studies of systemic infusion and local delivery for complications such as hand dysfunction (reduced grip strength, joint contracture, and impaired fine motor function) and digital vasculopathy have demonstrated feasibility, acceptable short-term safety, and encouraging signals in skin and vascular outcomes. Nevertheless, long term clinical benefit remains uncertain because published studies are few and heterogeneous in cell source, manufacturing and expansion protocols, dose, route, concomitant therapy, and endpoint selection. Progress in this area will require standardized potency frameworks, improved control of senescence and functional drift, phenotype-specific trial stratification, and harmonized outcome hierarchies across vascular and cutaneous domains. Integration of immune and vascular biomarkers as pharmacodynamic readouts, together with multicenter randomized controlled trials and long-term follow-up, will be essential for defining efficacy and advancing targeted cell-free therapeutic platforms in systemic sclerosis.</p>","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148971326","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Endodermal Organoids Along Two Axes: Single-Organ Fidelity, Inter-Organ Reconstruction, and the Unbuilt Gut-Lung Frontier.","authors":"Seungil Kim, Jangho Lee, Gun-Dong Kim","doi":"10.1007/s12015-026-11235-0","DOIUrl":"https://doi.org/10.1007/s12015-026-11235-0","url":null,"abstract":"<p><p>Three-dimensional organoids of the gut, liver, and lung have become mainstream models of human development, disease, and therapy. These organs share an embryonic endodermal origin, yet the field measures their progress inconsistently because the word \"maturity\" carries two unrelated meanings. Herein, we review the organoid work across all three organs and propose that the two orthogonal axes of advancement be analyzed separately. The first axis is single-organ fidelity. Adult stem cell organoids are faithful but partial, reproducing the adult epithelium of their source tissue with genomic stability yet lacking stromal, vascular, immune, and neural compartments. Human pluripotent stem cell organoids are complete but immature, co-emerging with multiple lineages yet arrested in a fetal-like state. The cost of each limitation is organ-dependent, smallest in the intestine, largest for hepatic drug metabolism, and most spatially defined across the proximal and distal lungs. The second axis is inter-organ reconstruction, where progress is strongly asymmetric. The gut-liver axis is comparatively advanced and sustained by linked organoid and microphysiological systems. The gut-lung axis, by contrast, remains the least-developed frontier, and no such linked organoid has yet been built. We therefore frame it as a proposal, using in vivo and correlative evidence to outline the design principles for such a model. Four bottlenecks recur across both axes: limited vascularization; batch-to-batch variability; organ-skewed immune, microbial, and stromal microenvironments; and unidirectional signaling. We argue that benchmarking models against single-cell developmental atlases and prioritizing construction of the gut-lung frontier should guide the field over the next decade.</p>","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148956433","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Primary Cilium: A New Player in Muscle Stem Cell Biology.","authors":"Anna Rausch de Traubenberg, Ludivine Rotard, Caroline E Brun","doi":"10.1007/s12015-026-11233-2","DOIUrl":"https://doi.org/10.1007/s12015-026-11233-2","url":null,"abstract":"<p><p>Adult muscle stem cells are responsible for skeletal muscle regeneration, a process where quiescent muscle stem cells activate, enter the cell cycle, and proliferate to give rise to either lineage-committed myoblasts for new muscle fiber formation, or self-renewing cells to replenish the stem cell reservoir. The regenerative capacity of muscle stem cells relies on their precise reception of environmental cues and appropriate intracellular responses. Quiescent muscle stem cells display a primary cilium, a microtubule-based organelle that protrudes from the cell surface and acts as a hub for chemical and mechanical signal transduction. Recent work has significantly increased our understanding of this organelle, demonstrating that the primary cilium actively regulates signaling pathways that are essential for maintenance of muscle stem cell quiescence, proliferation, and fate decision. In this review, we synthesize the current knowledge and recent advances on how this sensory organelle controls muscle stem cell quiescence, enables mechano-sensation, and regulates activation following tissue injury and during asymmetric self-renewal.</p>","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148956441","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Current Translational 3D In Vitro Models of Human Placental Tissue.","authors":"Ananya Raman, Niamh E P Mills, Louise Cole, Claire Richards, Lana McClements","doi":"10.1007/s12015-026-11231-4","DOIUrl":"https://doi.org/10.1007/s12015-026-11231-4","url":null,"abstract":"<p><p>Cellular models of placental tissue have the potential to recapitulate normal physiology, model disease, and facilitate therapeutic drug testing. In vivo or two-dimensional (2D) in vitro models of placental conditions have not been sufficiently representative of whole human tissue, thus have limited physiological relevance. This can be attributed to interspecies differences in placental physiology or a lack of structural complexity. In comparison, three-dimensional (3D) multicellular model systems provide a more sophisticated analogue of human placental tissue. Newer models of human placenta include 3D organoids, placenta-on-a-chip and organoid-on-a-chip, employing a range of materials and methods including pluripotent or trophoblast stem cells, microfluidics and 3D bioprinting. Accurately mimicking in vivo human tissue is crucial to the success of these translational 3D models of the placenta.In turn, a reliable representation of placental tissue architecture will allow discovery of the mechanisms underlying abnormal placental development and inform the prevention, diagnosis and treatment of pregnancy-related disorders such as preeclampsia and fetal growth restriction. Here, we provide a comprehensive critical appraisal of recent advances in 3D placental models, which aim to elucidate placental physiology, development and dysfunction. Additionally, we discuss how these platforms can accelerate the development of better monitoring and treatment strategies for pregnancy complications induced by a dysfunctional placenta.</p>","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148956410","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rewiring Cellular Context as A Central Mechanism Governing Cancer Stem Cell Survival: Insights from ESC Comparisons.","authors":"Yasin Ahmadi, Babak Elyasi Far, Sakhavat Abolhasani","doi":"10.1007/s12015-026-11217-2","DOIUrl":"https://doi.org/10.1007/s12015-026-11217-2","url":null,"abstract":"<p><p>Cancer stem cells (CSCs) drive tumor initiation, metastasis, and therapy resistance, yet their remarkable persistence remains poorly understood. While CSCs share stemness attributes with embryonic stem cells (ESCs), including self-renewal, transcriptional plasticity, and permissive chromatin, they exhibit a fundamentally divergent regulatory logic that prioritizes survival over developmental fidelity. ESCs maintain globally open chromatin that supports transcriptional hyperactivity but predisposes them to apoptosis under genotoxic stress, whereas CSCs maintain dynamically inducible, permissive chromatin at survival loci while repressing differentiation programs, enabling adaptive stress responses. We advance the hypothesis that CSC persistence emerges not from any single factor, but from the integrative rewiring of signaling cascades (Wnt/β-catenin, Notch, Hedgehog, PI3K/AKT/mTOR), stress-responsive transcription factors (HIFs, NF-κB, STAT3), and core pluripotency networks (OCT4, SOX2, NANOG) within a survival-centric context, reinforced by dynamic chromatin remodeling, inducible super-enhancer landscapes, and microenvironmental cues (hypoxia, inflammation, matrix stiffness). Within this framework, the E2F family serves as a key contextual integrator: in ESCs, constitutive E2F activity triggers p53-mediated apoptosis upon DNA damage, preserving genomic integrity; in CSCs, deregulated E2F activity redirects transcription toward DNA repair, antioxidant defenses, and anti-apoptotic programs. This functional divergence underscores that phenotypic outcome is determined by the broader cellular and epigenetic landscape rather than any single factor. We conclude that CSC persistence is an emergent property of this integrated, survival-centric program, fundamentally distinct from the developmental imperative of ESCs. Effective therapeutic strategies must therefore move beyond targeting individual pathways to dismantle the interconnected regulatory networks that define the CSC survival context, offering a more robust approach to overcome therapy resistance and prevent tumor relapse.</p>","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148945274","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"\"Extracellular Matrix Senescence in the Dermal Papilla: THSD4 Downregulation at the Crossroads of Hair Follicle Aging and Alopecia\".","authors":"Mamata Mishra, Rinky Kapoor, Pankaj Seth, Ashwin Prabhughate, Debraj Shome","doi":"10.1007/s12015-026-11234-1","DOIUrl":"https://doi.org/10.1007/s12015-026-11234-1","url":null,"abstract":"","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148945222","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}