STEM CELLS最新文献

{"title":"Correction to: Therapeutic Efficacy and Fate of Bimodal Engineered Stem Cells in Malignant Brain Tumors.","authors":"","doi":"10.1093/stmcls/sxag034","DOIUrl":"https://doi.org/10.1093/stmcls/sxag034","url":null,"abstract":"","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":"44 8","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148617498","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":"Regeneration of the mammalian brain: a relic of evolution?","authors":"Olena Zhulyn, Vanessa Donega","doi":"10.1093/stmcls/sxag029","DOIUrl":"10.1093/stmcls/sxag029","url":null,"abstract":"<p><p>Compared to amphibians, fish, and reptiles, mammals have an impaired capacity to regenerate the brain, despite the presence of a neural stem cell pool. Here, we consider the biological significance of a stem cell source in the human brain by exploring evolutionary trade-offs that may guide retention of regenerative capacity in mammals and the risks and benefits of active neurogenesis in adults. We discuss whether reduced regenerative capacity in humans is adaptive or stochastic and examine the role of the injured and diseased brain environment in preventing efficient brain repair. We discuss the therapeutic potential of activating the latent regenerative potential of the human brain to reverse tissue damage or degeneration and whether this approach carries with it an unanticipated risk of cancer.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13445984/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147872590","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":"Human iPSC-derived 3D cardiac models for cardiomyopathies: organoids, spheroids, and engineered heart tissues as translational platforms.","authors":"Prabin Upadhyaya","doi":"10.1093/stmcls/sxag039","DOIUrl":"10.1093/stmcls/sxag039","url":null,"abstract":"<p><p>Cardiomyopathies represent a substantial global health burden, yet progress in developing effective therapies was long constrained by the absence of physiologically relevant human models to understand molecular mechanisms and evaluating interventions. The advent of induced pluripotent stem cell (iPSC) technology has driven major advances in cardiomyopathy research, although important limitations persist. Current iPSC-based systems exhibit incomplete cellular maturation, lack functional vasculature and chamber level architecture, and possess an immature extracellular matrix. These factors must be carefully weighed when interpreting disease phenotypes and drug response data. Induced pluripotent stem cell-derived in vitro three-dimensional (3D) cardiac tissues have significantly addressed these issues, thereby expanding our ability to model human cardiac disease, offering more physiologically relevant platforms for mechanistic studies, drug screening, and translational research. This concise review synthesizes recent advances in the development of iPSC-derived 3D cardiac systems, such as 3D spheroids, engineered heart tissues, and cardiac organoids, their application to modeling various cardiomyopathies including hypertrophic cardiomyopathy, dilated cardiomyopathy, and amyloid-related cardiomyopathies, while discussing critical challenges including cellular maturation, vascularization, and standardization. In this review, emerging technologies and therapeutic strategies have been highlighted that bridge the gap between bench and bedside, demonstrating the translational potential of these models for precision medicine in cardiovascular disease.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13452171/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148409788","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":"Transforming growth factor beta-2 drives trabecular meshwork progenitor cell differentiation through SMAD2/3 signaling.","authors":"Xiaochen Fan, Emine K Bilir, Olivia A Kingston, Victoria R Kearns, Colin E Willoughby, Carl M Sheridan","doi":"10.1093/stmcls/sxag033","DOIUrl":"10.1093/stmcls/sxag033","url":null,"abstract":"<p><p>Primary open-angle glaucoma (POAG) is a major cause of irreversible blindness, yet its underly mechanisms remain unclear. Elevated intraocular pressure (IOP), the only modifiable risk factor for POAG, arises from increased resistance to aqueous humor outflow within the conventional outflow pathway, which comprises the trabecular meshwork (TM) and the inner wall of Schlemm's canal. Dysfunction and cellular loss within this pathway, particularly in the TM, are consistent features of the disease; however, the mechanisms responsible for impaired tissue maintenance and regenerative failure remain unclear. TM progenitor cells (TMPCs) have the capacity to replace lost TM cells, suggesting that impaired progenitor function may contribute to disease progression. Transforming growth factor beta 2 (TGFβ2), which is consistently elevated in the aqueous humor of POAG patients, plays a key role in regulating stem cell differentiation. We proposed that excess TGFβ2 disrupts TMPC function, leading to progenitor depletion and TM dysfunction. Here, we show that TGFβ2 drives TMPCs toward a differentiated, fibrotic phenotype, increasing TM and profibrotic gene expression while reducing progenitor markers. These effects are mediated through TGFβ2-SMAD2/3 signaling, as inhibition of this pathway preserves TMPC characteristics and suppresses fibrotic gene induction. Our findings identify TGFβ2-SMAD2/3 signaling as a regulator of TMPC fate in vitro and suggest a potential mechanism by which elevated TGFβ2 may influence TMPC behavior under pathological conditions.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13446226/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148025286","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":"Synergizing stem cells with biomaterials for therapeutic angiogenesis in ischemic diseases.","authors":"Taiyan Ji, Jiajia Shi, Jing Yang","doi":"10.1093/stmcls/sxag018","DOIUrl":"10.1093/stmcls/sxag018","url":null,"abstract":"<p><p>Therapeutic angiogenesis (TA) is a promising strategy for treating ischemic diseases, mainly by targeting the angiogenesis pathways and cells, particularly VEGF and endothelial progenitor cells. Although stem cell therapy has been extensively investigated, its clinical translation remains limited by challenges such as poor cell retention, low survival rates, and inefficient integration. In this review, we propose a mechanism-based framework of angiogenesis to discuss how biomaterials act synergistically with stem cells mainly through two distinct pathways: enhancing paracrine capacity and promoting direct differentiation of vascular lineage cells for vascular repair. Firstly, we go through the scientific literature and clinical studies, and summary the researches on biomaterials serve as artificial microenvironments to improve the retention and secretory function of mesenchymal stem cells (MSCs) and adipose-derived stem cells (ADSCs), thereby maximizing the release of angiogenic factors such as VEGF, bFGF, NGF, microRNA and so on. Secondly, we explore how functionalized biomaterials guide the in situ recruitment of endothelial progenitor cells (EPCs) and support the structural maturation of induced pluripotent stem cell (iPSC)-derived endothelial cells. By integrating these mechanism-driven approaches, we offer new perspectives on future directions for preclinical research and clinical translation of biomaterial-based therapies. Overall, this review has examined the role of individual stem cells and biomaterials, especially enhanced angiogenesis by stem cells focusing on their mechanisms of action and preclinical and clinical applications. We further discussed the challenges encountered by stem cell therapy in advancing to the stage of clinical transformation and considered future prospects.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147643405","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: Lack of a p21waf1/cip-Dependent G1/S Checkpoint in Neural Stem and Progenitor Cells After DNA Damage In Vivo.","authors":"","doi":"10.1093/stmcls/sxag040","DOIUrl":"https://doi.org/10.1093/stmcls/sxag040","url":null,"abstract":"","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":"44 8","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148756989","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":"MSC-derived small extracellular vesicles promote dental pulp repair by alleviating inflammation in pulpitis via AKT and p38 MAPK pathways.","authors":"Jiajun Shi, Yuanyuan Jiang, Shipin Zhang, Annie Shrestha, Xiaoli Hu, Lingyong Jiang, Wei Seong Toh","doi":"10.1093/stmcls/sxag038","DOIUrl":"10.1093/stmcls/sxag038","url":null,"abstract":"<p><strong>Background: </strong>Pulpitis compromises dental pulp defense and repair, and current therapies inadequately resolve inflammation. Mesenchymal stem/stromal cell (MSC)-derived small extracellular vesicles (sEVs) exhibit potent anti-inflammatory properties, yet their protective role in inflamed dental pulp and underlying mechanisms remain unclear. This study aimed to evaluate the therapeutic potential of MSC-sEVs in experimental rat pulpitis, define the contribution of sEV-associated CD73 activity, and elucidate the molecular mechanisms by which MSC-sEVs attenuate lipopolysaccharide (LPS)-induced inflammatory responses in dental pulp cells (DPCs).</p><p><strong>Methods: </strong>sEVs were enriched from human MSC-conditioned medium by size-based fractionation and characterized for particle size, protein concentration, and CD73/ecto-5'-nucleotidase (NT5E) activity. Rat pulpitis was induced by LPS application to Class I cavities of maxillary molars. In vitro inflammation was modeled using LPS-stimulated DPC spheroids. Inflammatory mediators were quantified by nitric oxide (NO) quantification and enzyme-linked immunosorbent assay (ELISA), while signaling pathways were examined by Western blotting and pharmacological inhibition of CD73, adenosine receptors, AKT, ERK, and p38 MAPK.</p><p><strong>Results: </strong>MSC-sEVs significantly alleviated pulpal inflammation and promoted reparative dentin formation in vivo, with efficacy comparable to mineral trioxide aggregate (MTA). In LPS-stimulated DPC spheroids, MSC-sEVs suppressed pro-inflammatory and nociceptive mediator release. Mechanistically, MSC-sEVs reduced NO, IL-6, MMP9, and NGF production through a CD73-adenosine receptor-dependent pathway involving AKT activation and p38 MAPK inhibition, but not ERK signaling.</p><p><strong>Conclusions: </strong>MSC-sEVs promote dental pulp repair by modulating inflammation through a CD73-mediated adenosine signaling axis, highlighting their potential as a cell-free therapeutic for early pulpitis intervention.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13452457/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148409839","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":"CircVapa promotes the abnormal differentiation of small intestinal epithelial stem cells in diabetic state.","authors":"Ti-Dong Shan, Wen-Jing Feng, Li Chen","doi":"10.1093/stmcls/sxag035","DOIUrl":"10.1093/stmcls/sxag035","url":null,"abstract":"<p><p>Diabetic enteropathy (DE) is a common complication of diabetes mellitus (DM), yet its underlying molecular mechanisms remain poorly understood. Emerging evidence suggests that abnormal differentiation of intestinal epithelial stem cells (IESCs) contributes to early intestinal dysfunction in DM. In this study, we aimed to investigate the role of CircVapa in regulating IESC differentiation and to elucidate the underlying molecular mechanism involving the miR-212-3p/Smoc2 axis. In this study, IESCs were extracted from BKS.CgDock7m+/+Lepr db/JNju (DM) mice models. A circular RNA molecule, CircVapa, was identified as being markedly enriched in IESCs. Experimental suppression of CircVapa in diabetic mice attenuated abnormal differentiation of intestinal epithelial cells (IECs). Notably, CircVapa was identified as a critical mediator of Lgr5+ stem cell functionality in hyperglycemic conditions. Mechanistically, microarray analysis, bioinformatics analysis, and luciferase reporter assays demonstrated that CircVapa serves as a competitive endogenous RNA (ceRNA) by directly binding miR-212-3p, thereby regulating Smoc2 expression. Furthermore, CircVapa regulated abnormal IESC differentiation via the miR-212-3p/Smoc2 regulatory network in diabetic mice. Collectively, this study demonstrates an important role of CircVapa in regulating IEC differentiation during DM progression.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148142178","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 transfer technologies with molecular insights into clinical applications.","authors":"Vahan Martirosian, Berney Peng, Michael A Teitell","doi":"10.1093/stmcls/sxag026","DOIUrl":"10.1093/stmcls/sxag026","url":null,"abstract":"<p><p>Mitochondria are essential cell signaling, survival, and bioenergetic organelles that uniquely harbor a maternally inherited, multicopy genome called mitochondrial DNA (mtDNA). The occurrence or accumulation of mtDNA mutations underlies a spectrum of inherited and acquired mitochondrial syndromes and diseases and is increasingly recognized as a source of metabolic plasticity, clonal fitness, and therapy tolerance in cancer. Recent studies have revealed mitochondrial transfer as a potential mode of intercellular communication that could compensate for mtDNA mutation-associated mitochondrial dysfunction. Transfer of mitochondria can restore homeostasis in stressed recipient cells by rebuilding respiratory capacity, rebalancing redox state, and reshaping cell fate. Reported mechanisms of transfer include tunneling nanotubes, extracellular vesicles, cell fusion, and others, such as macropinocytosis. Here, we review and evaluate emerging technologies developed for mitochondrial transfer studies and define the impact of transfer on cell physiology and pathology. We discuss translational opportunities for mitochondrial transfer-based interventions, as well as how mitochondrial exchange may represent a new framework for understanding tumor heterogeneity, adaptation, and aggressiveness.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13401490/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147866098","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":"Nail proximal fold stem cells participate in nail growth, orchestrating enhanced digit regeneration via bone morphogenetic protein signaling activation.","authors":"Anna Pulawska-Czub, Alicja Olczak-Cossu, Tomasz D Pieczonka, Krzysztof Kobielak","doi":"10.1093/stmcls/sxag028","DOIUrl":"10.1093/stmcls/sxag028","url":null,"abstract":"<p><p>Rodent and primate digit tips exhibit a remarkable regenerative capacity following amputation, driven by highly proliferative nail stem cells with active canonical Wnt signaling. Recently, a distinct, slow-cycling population of bi-functional nail proximal fold stem cells (NPFSCs) has been identified, contributing to both peri-nail epidermis and nail plate (NP). Here, we demonstrate that NPFSCs actively participate in nail growth, orchestrating digit regeneration, with bone morphogenetic protein (BMP) signaling serving as a key regulator. Inhibition of BMP resulted in an epidermalized NP-like structure with limited regeneration due to impaired Wnt pathway activation in the nail matrix cells. Conversely, BMP activation enhanced NPFSCs' involvement in the nail matrix and significantly promoted digit regeneration. We further revealed that enhanced BMP activity not only accelerated nail and bone regrowth but also extended the regenerative boundary proximally, enabling full regeneration after up to ∼60% removal of the distal phalanx (P3). Moreover, in BMP gain-of-function models, extreme proximal amputation, removing the majority of the P3, still permitted partial NP regeneration despite the absence of bone reconstruction. Finally, we isolated and cultured lineage-traced NPFSCs and transplanted them into immunocompromised mice, where they integrated into the nail proximal fold and contributed to nail matrix progenitors during regeneration. Transplanted NPFSCs retained their regenerative capacity in vivo, highlighting their therapeutic potential. Collectively, our findings identify a pivotal role of BMP signaling in mediating NPFSC-driven digit regeneration, reveal BMP-Wnt cross-talk as essential to this process, and provide a framework for enhancing regenerative outcomes in previously non-regenerative contexts following traumatic amputation.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13401488/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147855522","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}