Proteomics and human microchips identify Thrombospondin-1 as a potential biomarker for calciphylaxis stem cell therapy.

Tandem single-cell epigenetic and transcriptomic analysis reveals spatiotemporally distinct genomic features among testis cell lineages.

Stem cells as emerging regenerative approaches for post-traumatic stress disorder: Mechanisms and translational challenges.

Exosome-mediated crosstalk in rheumatoid arthritis: Pathogenic mediators to next-generation therapeutics.

Prediction of tumor control probability in prostate cancer radiotherapy using a biophysical model incorporating cancer stem cell and hypoxia.

A pH-sensitive nanococktail enabled cancer stem cell elimination, deep tumour penetration, and tumour shrinkage.

A bilayer hydrogel enables spatiotemporal delivery of distinct hepcidin forms to reprogram macrophage responses for repair of infected bone defect.

PGK1/PHGDH axis drives radioresistance in glioblastoma stem cells.

A function-first legacy in hematopoietic stem cell biology: the scientific impact of Hal E. Broxmeyer.

Calmodulin (CaM) is a central calcium sensor and signaling hub that critically governs stem cell fate. However, directly intracellular modulation of CaM remains challenging due to its activity is tightly coupled to finely balanced calcium homeostasis, and conventional chemicals or biomaterials have limited ability to access or target it. Here, we introduce a novel two-dimensional, porous, covalent triazine-based framework, CTF-Ca, synthesized under ambient conditions, that offers a new strategy for intracellular CaM regulation. Unlike conventional approaches, CTF-Ca bypasses membrane calcium channels, enabling direct calcium influx into mesenchymal stem cells (MSCs) and triggering robust, sustained activation of the Ca2+/CaM signaling pathway. This activation markedly enhances osteogenic differentiation in MSCs. Remarkably, CTF-Ca also compensates for suppressed CaM function, restoring osteogenic potential in MSCs even under CaM-inhibited conditions. This compensatory effect was further demonstrated in C2C12 myogenic progenitor cells, a skeletal muscle model characterized with high endogenous CaM expression, where CTF-Ca rescued myotube formation in CaM deficient cells, underscoring its broad applicability. Together, these findings establish CTF-Ca as an effective 2D material for direct intracellular modulation of CaM, offers a promising new tool for regulating stem and progenitor cells fate.

Drosophila male germline stem cells (GSCs) reside at the testis tip, surrounding a cluster of niche cells known as the hub. Bone Morphogenetic Protein (BMP) ligands secreted from the hub exert both contact-dependent and -independent effects. In close proximity to the niche, BMP signaling maintains stem cells by suppressing transcription of the key differentiation factor Bag of Marbles (Bam). In contrast, the diffusible fraction of BMP promotes differentiation of cells by activating bam expression. How a single signaling pathway produces such opposing outcomes has remained unclear. Here, we show that the diffusible BMP fraction induces bam transcription by repressing the transcriptional repressor Brinker (Brk). We further found that brk mRNA and protein display a highly heterogeneous distribution pattern within interconnected spermatogonia, suggesting that Brk has a distinct role in a subset of transit-amplifying cells. Taken together, our findings suggest a mechanism whereby a single niche-derived factor modulates reciprocal outcomes inside versus outside the niche, which is essential for tissue homeostasis. Given the widespread role of BMP signaling across stem cell niches, this mechanism might represent a general strategy for balancing stem cell self-renewal and differentiation.

Development of muscle contractures is common in cerebral palsy (CP) and is characterized by high muscle stiffness that limits function and mobility. However, the state of stem cells within contracture, particularly muscle stem cells and fibroadipogenic progenitors, is largely unknown. This study leverages single cell RNA sequencing technology to determine how specific cell types are altered in the contracture environment. Skeletal muscle biopsies were collected from children with CP or typically developing (TD) children undergoing surgery. The 10X Genomics platform was used on tissue from n = 3 patients per condition. Significant changes in CP compared to TD were investigated within individual cell types for differentially expressed genes, gene ontologies, cell subpopulations, and predicted interactions. CP muscle stem cells demonstrated significant upregulation of fibrotic genes and downregulation of myogenic genes compared to typically developing. Fibroadipogenic progenitors in CP showed the emergence of a significant proportion of a highly profibrotic subpopulation, leading to the most dramatically upregulated genes in CP also being extracellular matrix constituents. Interacting signals between fibroadipogenic progenitors, muscle stem cells, and immune cells were identified that support contracture progression. Contracture is associated with reduced myogenic transcriptional features in muscle stem cells and enhances fibrotic signals in muscle stem cells and fibroadipogenic progenitors that perpetuate contracture. The study reveals specific genes and signaling pathways as therapeutic targets to reduce muscle contracture in children with CP.NEW & NOTEWORTHY The development of skeletal muscle contractures in cerebral palsy is a major component of disability. However, little is known about how contracture influences stem cells. This study is the first to apply single cell RNA sequencing technology to muscle contractures of children with cerebral palsy. The analysis reveals muscle stem cells with reduced myogenic transcription. Critically, a profibrotic subpopulation of fibroadipogenic progenitors is revealed in contracture. Additionally, cell-cell signaling analysis identifies potential therapeutic targets.

Platelet transfusions are essential for managing thrombocytopenia but have critical limitations, including a 5-7-day shelf-life causing wastage, alloimmune refractoriness in chronically transfused patients, and vulnerability to supply disruptions. Ex vivo platelet production from stem cells represents a transformative solution, evolving from initial hematopoietic stem cell approaches to induced pluripotent stem cell platforms with unlimited expansion and genetic tractability for universal platelet products. We critically reviewed the state and future trajectory of ex vivo platelet production, focusing on stem cell sources, manufacturing innovations, QC methods, and progression from laboratory concept to clinical reality. Key advances include immortalized megakaryocyte progenitor cell lines for scalable manufacturing; turbulence-based bioreactors that harness physiological shear stress to produce over 100 billion platelets/run; and comprehensive quality frameworks spanning cellular and molecular characterization, functional assays, and in vivo validation. We comparatively analyzed pioneering first-in-human clinical trials that collectively established the safety of iPSC-derived platelet transfusion and highlighted the translational challenges of achieving donor-comparable efficacy. We also highlighted the evolving corporate landscape, wherein companies pursue commercialization alongside national initiatives, including Korea's 15-yr artificial blood program. Convergence between biological insight, engineering innovation, and sustained investment suggests that ex vivo platelet production can transform transfusion medicine. Remaining challenges include reducing costs and optimizing in vivo circulation of platelet products. Initial implementation will likely focus on high-value applications, such as transfusion for alloimmunized patients, before broader adoption. The long-term goal is to replace the vulnerable donor-dependent system with on-demand production of standardized, pathogen-free, and universally compatible platelets.

This study aimed to investigate the effects of different copper sources (copper sulfate and copper glycinate) on growth performance, trace element metabolism and intestinal stem cell activity in growing pigs. In experiment 1, 30 castrated male pigs (Landrace × Large White; initial body weight of 43.11 ± 1.20kg) were randomly assigned to three treatment groups (n = 10): (1) high-dose CuSO₄ group (150mg/kg Cu as CuSO₄•5H₂O), (2) low-dose CuSO₄ group (20mg/kg Cu as CuSO₄•5H₂O), (3) Cu-Gly group (20mg/kg Cu as copper glycinate). The trial lasted for 30 days. The results showed that pigs fed 20mg/kg Cu as Cu-Gly had final body weight (P = 0.247) and weight gain (P = 0.732) comparable to those fed 150mg/kg Cu as CuSO₄, while exhibiting a significantly improved feed conversion ratio. Additionally, hepatic iron concentration in the Cu-Gly group was significantly higher than in the high-dose CuSO₄ group, whereas renal copper accumulation was lower. Fecal copper excretion in the Cu-Gly group was reduced by 76.38% compared to the high-dose CuSO₄ group(P < 0.0001). In experiment 2, an in vitro porcine small intestinal organoid culture system was employed. Our results indicated that the lower dose of copper markedly improved intestinal organoid budding and stem cell amplification (P < 0.01), and Cu-Gly significantly improved the intestinal organoid surface area and stem cell differentiation (P < 0.001). Simultaneously, the high dose of copper treatment significantly inhibited the minerals transported related gene expression (DMT1, ZIP4, CTR1, ZIP8), but induced the MT1A and MT3 expression in organoids (P < 0.01). Thus, our study finds a relatively effective way to substitute for pharmacological doses of copper, probably via regulating the minerals metabolism and improving the intestinal stem cell proliferation and differentiation.

Stem cells at the tumor frontier: Mechanistic insights, therapeutic challenges, and emerging horizons.

True regeneration of the pulp-dentine complex is the ultimate goal of regenerative endodontic procedures (REPs). Despite favourable clinical outcomes, such as resolution of apical periodontitis, continued root elongation and apical closure, histological evidence suggests that most clinical cases result in tissue repair rather than true regeneration. This discrepancy arises from the intricate requirements for optimising the microenvironment, which encompasses two essential stages: disinfection and regeneration. These two stages are not necessarily sequential; they can overlap and be highly interconnected, influencing each other. Current REPs protocols have limitations in both disinfection and regeneration. Endodontic biofilms exhibit a notable tolerance to disinfectants and have the capability of recovery, which negatively affects the odontogenic potential of stem cells. Additionally, immune cells, particularly M1 and M2 macrophages, interact with stem cells and affect their regenerative capacity. Standard irrigants and intracanal medicaments often fail to eliminate biofilms, compromising stem cell viability and differentiation potential. On the regeneration side, age-related decline in stem cell function reduces cell survival and differentiation capacity, while insufficient delivery and lack of control over signalling molecules limit odontogenesis, angiogenesis, and neurogenesis. Commonly used scaffolds for REPs lack the structural, biochemical and biological precision required to guide regeneration of well-organised tissue. Furthermore, a microenvironment characterised by hypoxia, restricted nutrients and limited neurovascular ingrowth further constrains regenerative outcomes. This review will focus on the limitations of the current regenerative microenvironment in REPs and discuss emerging strategies aimed at integrating infection control with tissue engineering design. It also highlights the need for novel antimicrobial approaches and advanced tissue engineering strategies in REPs. Multifunctional biomaterials, such as chitosan nanoparticles, antimicrobial peptides and hierarchically structured scaffolds, may ultimately facilitate true biological regeneration of the pulp-dentine complex.

The p75NTR/Mdm2 signaling axis promotes odontogenic differentiation and mineralization in ectomesenchymal stem cells.

Nasopharyngeal Carcinoma (NPC) tumor stem cells play a crucial role in the occurrence and development of nasopharyngeal carcinoma, but the identity and role of Cancer Stem Cell (CSC) subpopulations that drive metastasis remain unclear. This study explores the mechanisms of NPC stem cell subpopulations (CXCR4+) in the development of NPC, providing a reference for therapeutic targets for NPC. Immunohistochemical analysis of CXCR4 expression was performed in 71 NPC and 5 chronic nasopharyngitis tissues. Stemness, tumorigenicity and Epithelial-Mesenchymal Transition (EMT) profiles were established for cells in tumor spheres by flow cytometry (CD133/CXCR4), functional assays, Quantitative Reverse Transcription Polymerase Chain Reaction (RT-qPCR) and Western blotting. CXCR4+ cell metastatic potential was evaluated in a mouse NPC model. CXCR4 expression correlated with NPC T and N stage. CD133+ and CXCR4+ cells were enriched in the tumor sphere. CXCR4+ subsets had enhanced self-renewal (The CXCR4-positive subgroup exhibited a 45% increase in the ability to form tumor spheres), spindle morphology and migration/invasion with upregulation of markers of EMT, Snail, Twist, Vimentin, N-cadherin, stemness, Oct4, Nanog, Sox2 and downregulation of E-cadherin. CXCR4+ tumorsphere cells potentiated metastatic lung nodules in vivo via SDF-1/CXCR4 signaling, giving a 500% increase relative to controls. A metastatic CSC subpopulation present in NPC express CXCR4 and have activated EMT and SDF-1/CXCR4-driven metastasis. CXCR4 may have utility as a biomarker and the SDF-1/CXCR4 axis may be a therapeutic target for NPC.

The scalability of cultivated meat production depends on cost-effective, edible scaffolds that support attachment, proliferation and differentiation of adherent cells whilst meeting food safety and sensory requirements. However, most existing microcarriers are synthetic or of animal-origin, limiting their compatibility with food applications, increasing downstream processing costs, and raising ethical and environmental concerns associated with animal use. For the first time, we present mycelia-based microcarriers derived from food-grade Penicillium strains used in cheese production, as scaffolds for cultivated meat. Eight strains, including novel variants developed through non-GMO techniques (sexual breeding and ultraviolet mutagenesis), were screened for cytotoxicity using bovine adipose-derived stem cells. Out of these, four strains (P. camemberti Myc1; P. roqueforti Myc2, Myc3 and Myc4) were selected for further evaluation based on non-cytotoxic behaviour, ease of handling and pellet size comparable to commercial microcarriers. Morphological characterisation revealed that these strains form highly porous, fibrous pellets with estimated specific surface areas of approximately 4400–5100 cm2/g, providing a favourable architecture for cell growth. All four microcarriers supported strong initial cell attachment, meeting or exceeding industry benchmarks for mesenchymal stem cells in both serum-containing and animal-free media. Growth kinetics diverged between strains, with Myc3 and Myc4 displaying the highest growth rates (≥2-fold increase; μ ≈ 0.015 h−1), and doubling times of 47–48 h. These findings highlight the great promise of fungal pellets for the development of edible scaffolds for cultivated meat production, helping to address a central bottleneck in bringing affordable, high-quality protein to consumers.

Renewed interest in the application of ascorbic acid for anti-tumor therapy led to the discovery of its effect on cancer stem cells (CSC), a small group of cells in tumor bulk with specific properties that enable them to resist conventional therapy and metastasize. The application of ascorbate in high concentrations has a prooxidative effect on cancer cells, causing extensive oxidative stress that can induce cell death. Therefore, the aim of the study was to explore the effect of ascorbate delivered by nanoparticles on patient-derived CSC. We previously synthesized and characterized solid lipid nanoparticles containing ascorbyl palmitate (SLN-AP), a more stable lipid derivative of ascorbate. SLN-coumarin-6 were applied for visualization of the cellular uptake of the SLN. SLN-AP were applied to sarcoma stem cells isolated from samples of six patients to test their cytotoxicity and effect on oxidative stress in CSC. SLNs with incorporated coumarin-6 enter the cells gradually, however, CSC react with abrupt generation of vesicles of a wide range of sizes (up to 20 μm). SLN-AP have higher IC50 values in osteosarcoma CSC than in soft tissue sarcomas. Nanoparticles without incorporated AP show strong cytotoxic effect. The treatment with nanoparticles shows antioxidative effect in CSC. Soft-tissue sarcoma stem cells were more sensitive to the treatment than osteosarcoma stem cells and cytotoxicity is not due to oxidative stress. SLN-AP formulation should be further optimized to reduce the cytotoxicity of SLNs and to reduce their efflux from the CSC population.