Stem Cell Reviews and Reports最新文献

{"title":"From Ferroptotic Stress to Stemness: TNT-Mediated EMT Plasticity in Cancer Progression.","authors":"Aishani Sengupta, Priya Samanta, Jhinuk Basu, Souradeep Biswas, Shampa Pakhira, Mrinmoyee Mondal, Prosenjit Saha, Subhadip Hajra","doi":"10.1007/s12015-026-11179-5","DOIUrl":"10.1007/s12015-026-11179-5","url":null,"abstract":"<p><p>Tumor evolution is shaped by adaptive responses to metabolic and oxidative stress, rather than solely by genetic mutations. Ferroptosis is an iron-dependent mechanism of cell death driven by lipid peroxidation. This process acts both as a tumor suppressive barrier and as a selective pressure for tumor adaptation. Cancer cells that escape ferroptosis undergo metabolic and transcriptional reprogramming, resulting in enhanced antioxidant capacity and increased resistance to oxidative stress. These adaptative changes closely intersect with epithelial-mesenchymal transition (EMT), generating hybrid phenotypes enriched in cancer stem cell (CSC)-like properties. Concurrently, tunneling nanotubes (TNTs) emerge as stress-responsive intercellular communication networks that facilitate the transfer of mitochondria, metabolites and redox regulators, thereby enabling cooperative survival. Through this review, we outline an integrative framework connecting ferroptosis, EMT plasticity, TNT-mediated communication and CSC dynamics, offering insights into novel strategies to overcome therapeutic resistance, prevent metastatic dissemination and limit tumor relapse. It further highlights the current landscape of emerging biomarkers and therapeutic agents that may enable the translation of this integrated network as a target in cancer treatment.</p>","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":"2824-2845"},"PeriodicalIF":4.9,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148278881","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":"Decoding, Mapping, and Designing: A New Paradigm for Harnessing Umbilical Cord Mesenchymal Stem Cell Heterogeneity in Obstetric Precision Therapy.","authors":"Zhang-Lu An, Zhi-Ming Wang, Wen-Hao Zhao, Li-Juan Peng, Er-Meng Gao","doi":"10.1007/s12015-026-11168-8","DOIUrl":"10.1007/s12015-026-11168-8","url":null,"abstract":"<p><p>Umbilical cord mesenchymal stem cells (UC-MSCs) are attractive candidates for obstetric regenerative medicine because of their accessibility, proliferative capacity, and broad immunomodulatory repertoire. Yet clinical translation remains constrained by inter-donor and intra-product heterogeneity, unstable potency readouts, and the absence of a reproducible framework that links molecular states to disease-specific therapeutic needs. In this revised review, we refine the \"Decode-Map-Design\" paradigm into a structured translational workflow. \"Decode\" integrates single-cell and spatial omics, donor metadata, and orthogonal potency assays to define operational functional states rather than assuming fixed subtypes. \"Map\" aligns these states with dominant pathobiologic modules in obstetric disorders-including immune dysregulation, vascular injury, metabolic stress, and extracellular matrix remodeling-to enable mechanism-based matching. \"Design\" then uses atlas-guided isolation, microenvironmental priming, genetic engineering, and standardized cell-free formulation to build products with predefined release criteria. We further incorporate the principal barriers that currently limit implementation, including marker instability across laboratories, culture-driven state drift, assay standardization, GMP scalability, regulatory classification, cost, and the paucity of subtype-guided clinical data. A worked preeclampsia case study is provided to illustrate an end-to-end pipeline from atlas discovery to early-phase trial design. We argue that UC-MSC heterogeneity should be treated neither as noise nor as a guarantee of efficacy, but as a measurable and engineerable source of therapeutic optionality. The framework remains hypothesis-generating, and requires validation in human-relevant models and prospective clinical studies, but it offers a practical roadmap for converting heterogeneous UC-MSC products into safer and more precise obstetric therapeutics.</p>","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":"2724-2739"},"PeriodicalIF":4.9,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148158173","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":"Primordial Germ Cell Development in Teleosts: Their Origin, Fate and Role in Sex Determination.","authors":"Komeil Razmi, Chris G Carter, Jawahar Patil","doi":"10.1007/s12015-026-11169-7","DOIUrl":"10.1007/s12015-026-11169-7","url":null,"abstract":"<p><p>In the context of sexual reproduction, primordial germ cells (PGCs) are the progenitors of life; they develop into gametes and safeguard fertility. By virtue of their diverse reproductive strategies, fishes provide appealing models to study germ cell formation and functional gonadogenesis. This review aims to consolidate our understanding of PGC development in teleosts by evaluating the developmental milestones of germ cell formation in contrast with other model animals. Here, we revisit germ plasm assembly in gametes, re-examining the extent and nature of parental contributions to germ cell inheritance. We further examine how germ cell fate in teleosts is governed by germ plasm inheritance, whereby lineage identity arises through selective retention and stabilisation of maternal determinants rather than de novo specification. Following this, we demonstrate that a coordinated network of molecular pathways and effector genes drives PGC signalling, mobilization, and homing to the gonadal niche. Then, we highlight that, in contrast to mammals, teleost germ cell specification is largely uncoupled from genome-wide epigenetic reprogramming and instead relies on maternally inherited messages and post-transcriptional regulation to establish germline identity. Finally, we explore the interplay between newly harboured germ cells and gonadal somatic cells that underpins sexual identity acquisition. Collectively, these findings establish a conceptual framework in which germ plasm inheritance, post-transcriptional regulation, and soma-germline interactions jointly govern germ cell fate, sexual identity, and functional fertility in teleosts.</p>","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":"2788-2807"},"PeriodicalIF":4.9,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148272641","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":"hsa-let-7c-3p Restrains the Proliferation-to-Osteogenesis Transition of Human Periodontal Ligament Mesenchymal Stem/Stromal Cells via NT5E.","authors":"Ye Yint Kaung Myint, Anhao Liu, Jingyi Gao, Masahiro Hatasa, Supreda Suphanantachat Srithanyarat, Takanori Iwata","doi":"10.1007/s12015-026-11160-2","DOIUrl":"10.1007/s12015-026-11160-2","url":null,"abstract":"<p><p>Small extracellular vesicles (sEVs) derived from mesenchymal stem/stromal cells (MSCs) contain microRNAs (miRNAs) that can modulate the cellular behavior of recipient cells. Human periodontal ligament mesenchymal stem/stromal cells (hPDL-MSCs) are a unique MSC population involved in periodontal tissue regeneration; however, the specific miRNAs that regulate their proliferative and differentiation-related properties remain incompletely understood. In this study, we profiled miRNAs enriched in sEVs secreted by highly proliferative human PDL-MSCs and identified hsa-let-7c-3p as a candidate regulator of hPDL-MSC behavior. Functional assays demonstrated that hsa-let-7c-3p enhanced proliferative and migratory behavior, reflected by an approximately 1.5-fold increase in metabolic activity and a 2-fold increase in migration, while suppressing osteogenic differentiation, with approximately 50% reductions in alkaline phosphatase activity and mineralization. To identify functionally relevant downstream targets, we intersected AGO2-RIP-seq-enriched transcripts, RNA-seq-defined genes altered by hsa-let-7c-3p overexpression, and in silico target predictions, identifying NT5E/CD73 as a candidate downstream target with experimental validation. Furthermore, NT5E knockdown partially phenocopied the effects of hsa-let-7c-3p overexpression on hPDL-MSC proliferation, migration, and osteogenic differentiation, supporting a functional link between hsa-let-7c-3p and NT5E/CD73. These findings highlight hsa-let-7c-3p as an underexplored sEV-associated 3p miRNA strand that restrains the proliferation-to-osteogenesis transition of hPDL-MSCs and identify NT5E/CD73 as a functionally relevant downstream target. Clinical trial number. Not applicable.</p>","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":"2863-2878"},"PeriodicalIF":4.9,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13354647/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148151191","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Induced Pluripotent Stem Cell-Derived NK Cells as an Off-the-Shelf Platform for Cancer Immunotherapy: Opportunities, Challenges, and Clinical Translation.","authors":"Shiva Mosadegh Manshadi, Maryam Mehravar, Abbas Hajifathali, Elham Roshandel, Saeid Kaviani Jabali","doi":"10.1007/s12015-026-11156-y","DOIUrl":"10.1007/s12015-026-11156-y","url":null,"abstract":"<p><p>In recent years, off-the-shelf cellular immunotherapies have attracted much attention as a practical alternative to autologous therapies. Within this landscape, induced pluripotent stem cell-derived natural killer cells (iPSC-derived NK cells; iPSC-NK) have emerged as a highly versatile platform because they combine renewable starting material, batch-to-batch uniformity, favorable intrinsic safety, and amenability to precise genetic engineering.This review places iPSC-NK cells within the broader field of NK cell-based immunotherapy by comparing them with peripheral blood-derived NK cells, umbilical cord blood-derived NK cells, and NK cell lines, including clinically explored NK-92-based platforms, and by outlining key distinctions between NK cell therapies and CAR-T approaches. We summarize current strategies for iPSC-to-NK differentiation, spanning feeder-based systems, feeder-free protocols, embryoid body approaches, and scalable GMP-compatible manufacturing methods. We further discuss genetic engineering strategies for NK cells, with particular emphasis on genetic tuning as a systems-level framework for coordinating CAR signaling, cytokine responsiveness, and activation-inhibition balance to improve antitumor efficacy while preserving functional stability and clinical safety. In addition, this review examines translational challenges that continue to limit broader NK-cell adoption, including incomplete functional maturation, limited persistence, donor- and source-dependent variability, manufacturing standardization, cryopreservation, and quality-control requirements. Early clinical studies of iPSC-NK products indicate a favorable safety profile and preliminary antitumor activity in selected hematologic malignancies, although durable efficacy and broader validation in solid tumors remain to be established. Importantly, iPSC-NK cells should be considered one of several complementary NK-cell platforms rather than a definitive or universally superior strategy. Overall, current evidence supports iPSC-NK cells as a promising programmable off-the-shelf platform, but their ultimate clinical impact will depend on achieving reproducible large-scale manufacturing, balanced genetic engineering, and consistent in vivo performance relative to other NK-cell sources and established CAR-T therapies.</p>","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":"2671-2690"},"PeriodicalIF":4.9,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148035287","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":"Advances in Oral Cavity Stem Cell Research Revealed through Multi-omics Analysis.","authors":"Sachio Tsuchida, Hiroshi Umemura, Masaki Nakajima, Kazuhide Iizuka, Isamu Shimazaki, Elisa Shikata, Tomohiro Nakayama","doi":"10.1007/s12015-026-11119-3","DOIUrl":"10.1007/s12015-026-11119-3","url":null,"abstract":"<p><p>Oral stem cell research encompasses the study of dental pulp stem cells, periodontal ligament stem cells, regeneration of dental pulp and periodontal ligament, and therapeutic approaches for dental caries. Dental pulp stem cells, located in the oral cavity, have been applied to tooth, alveolar bone, and periodontal tissue regeneration and are anticipated to exert systemic therapeutic effects. Global efforts to identify biomarkers of oral disease have employed expression proteome analysis. However, because most proteins function only after undergoing post-translational modifications, methods based solely on expression proteomics remain limited. Consequently, increasing attention has focused on characterizing protein modifications. Advances now enable comprehensive measurement of modifications across the omics hierarchy, including the epitranscriptome, phosphoproteome, and metabolome, to clarify the layered interactions among the genome, epigenome, transcriptome, and metabolome. \"Multi-omics\" denotes the integration of multiple omics layers for analysis. Moreover, several omics layers can now be assessed at single-cell resolution, enabling a more detailed projection of biological phenomena and a more holistic understanding. Recently, multi-omics strategies have also been applied to oral stem cell research. This review summarizes emerging insights into oral cavity stem cell biology obtained through multi-omics approaches. We recognize the limitation that our search strategy relied exclusively on the MEDLINE database in PubMed and did not incorporate additional sources such as gray literature, conference proceedings, or clinical practice guidelines. Multi-omics analysis enables the elucidation of multilayered causal relationships in biological phenomena that were previously inaccessible using conventional single-omics approaches, by integrating multiple layers such as the genome (DNA), transcriptome (RNA), proteome (proteins), and metabolome (metabolites). Looking forward, the integration of AI and machine learning is expected to facilitate early diagnosis of oral diseases, precise patient stratification, and the advancement of personalized medicine.</p>","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":"2143-2158"},"PeriodicalIF":4.9,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147718128","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":"Hypoplastic Left Heart Syndrome Cardiomyocytes Exhibit Intrinsic Stress Vulnerabilities and Augmented Stress Responses in vitro.","authors":"Margarida Varela, Minna Ampuja, Martin Broberg, Amanda Ramste, Virpi Talman, Emmi Helle","doi":"10.1007/s12015-026-11127-3","DOIUrl":"10.1007/s12015-026-11127-3","url":null,"abstract":"<p><strong>Background: </strong>Hypoplastic left heart syndrome (HLHS) is a severe congenital heart defect characterised by underdevelopment of left-sided cardiac structures. While genetic predisposition contributes to HLHS, the relevance of environmental stressors is increasingly recognised, yet the cellular mechanisms linking genetic susceptibility to environmental vulnerability remain unclear. We aimed to identify molecular and functional differences between cardiomyocytes derived from HLHS patients and healthy controls to uncover potential susceptibilities contributing to the HLHS phenotype.</p><p><strong>Methods: </strong>Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) from HLHS patients and healthy controls were used to examine intrinsic cellular differences. Single-cell RNA sequencing compared baseline transcriptional profiles. Functional assays assessed responses to endothelin-1 (ET-1)-induced stress, cyclic mechanical stretch, and basal or mitogen-stimulated proliferation. These approaches were used to identify intrinsic functional impairments and altered stress responses in HLHS cardiomyocytes.</p><p><strong>Results: </strong>Single-cell transcriptomics revealed downregulation of gene networks associated with cardiac stress responses, metabolic resilience, and rhythm regulation in HLHS cardiomyocytes. Regulon analysis revealed broad reductions in transcription factor activity across key cardiac regulatory networks. Functionally, HLHS cardiomyocytes showed heightened vulnerability to ET-1, with exaggerated proBNP induction compared with controls. No significant differences were observed following cyclic mechanical stretch. Basal proliferation varied across HLHS lines, while mitogen-induced proliferation remained comparable to controls.</p><p><strong>Conclusions: </strong>These findings support a model in which intrinsic molecular and functional vulnerabilities in HLHS cardiomyocytes might reduce resilience to developmental stressors. Such gene-environment interactions may contribute to HLHS pathogenesis, underscoring the interplay between genetic predisposition and environmental influences in congenital heart disease.</p>","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":"2549-2567"},"PeriodicalIF":4.9,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13241447/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147842979","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dental Pulp Stem Cells for Modelling Osteoarthritis.","authors":"Manoj Bansode, Rajesh Kumar Gupta, Ramesh Bhonde, Avinash Kharat","doi":"10.1007/s12015-026-11109-5","DOIUrl":"10.1007/s12015-026-11109-5","url":null,"abstract":"","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":"2622-2624"},"PeriodicalIF":4.2,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147639946","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":"\"Hair Follicle Stem Cells and their Lymphatic Niche: An Overlooked Axis in Cutaneous Regeneration\".","authors":"Rinky Kapoor, Varad Rajendra Saptarshi, Raji Patil, Debraj Shome","doi":"10.1007/s12015-026-11150-4","DOIUrl":"10.1007/s12015-026-11150-4","url":null,"abstract":"","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":"2649-2651"},"PeriodicalIF":4.2,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147864536","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":"Integrating Single-Cell Sequencing and Proteomics to Unravel Stem Cell Heterogeneity: Implications for Precision Regenerative Medicine.","authors":"Mohammed Zayed, Ahmed Massoud, Roya Al-Haddad, Ahmed Al-Kubaisi, Walid Said, Amany Atiaa, Byung-Hoon Jeong","doi":"10.1007/s12015-026-11116-6","DOIUrl":"10.1007/s12015-026-11116-6","url":null,"abstract":"<p><p>Stem cell populations are inherently diverse, consisting of distinct subtypes with unique molecular signatures, self-renewal capacities, and differentiation potentials. This natural variability complicates their clinical use, leading to unpredictable treatment outcomes and safety concerns in regenerative medicine. Traditional bulk analysis methods obscure this vital cellular diversity by providing average data. Therefore, studying stem cell heterogeneity at the single-cell level is crucial for developing reliable and precise therapeutic strategies. This review examines how integrating single-cell sequencing with proteomics technologies enhances the current understanding of stem cell biology. We discuss how single-cell RNA sequencing reveals transcriptomic diversity, identifies rare subpopulations, and traces lineage pathways. Additionally, we highlight emerging single-cell proteomic techniques, such as mass cytometry and high-sensitivity mass spectrometry, which directly analyze functional protein expression and signaling networks that ultimately define cellular phenotypes. Combining these methods provides a comprehensive view of stem cell states, offering insights into the molecular mechanisms that influence fate decisions and responses to external signals. Ultimately, these advances enable precision regenerative medicine by improving cell characterization and developing tailored differentiation strategies for safe and effective clinical applications.</p>","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":"2061-2083"},"PeriodicalIF":4.9,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147639923","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}