Long QT syndrome is clinically associated with recurrent ventricular tachycardia and sudden cardiac death. Mutations in KCNH2, which encodes the pore-forming potassium channel subunit human ether-a-go-go-related gene (Kv11.1), are associated with long QT syndrome type 2 (LQTS2).

Glioblastoma (GBM) is an aggressive brain cancer infiltrated by immunosuppressive myeloid-derived suppressor cells (MDSCs) and confers poor prognosis. To address this, our group developed an adoptive cellular therapy platform specifically for primary central nervous system (CNS) malignancies that yielded significant survival benefits against multiple brain cancer models. Preclinically, this platform establishes proof-of-concept for lymphodepletion achieved through host conditioning with total body irradiation (TBI). While host conditioning is thought to remove immunosuppressive elements, the aim of this study was to determine how immune recovery is affected by adoptive cellular therapy.

There is an urgent need for novel targeted therapeutic strategies for pediatric-type diffuse high-grade glioma (PDHGG) to improve patient outcomes, the development of which demands model systems that accurately recapitulate the specific PDHGG subtypes. Characterization, longitudinal monitoring and, ultimately, evaluation of treatment response in these models requires sensitive non-invasive imaging techniques such as magnetic resonance imaging (MRI).

Scalable manufacturing of human induced pluripotent stem cells (iPSCs) is essential for industrial-scale production of cell therapies and regenerative medicines. However, the 3D aggregate cultures used in manufacturing exhibit substantial spatial and metabolic heterogeneity compared with the relatively homogeneous monolayer systems used in laboratory studies, complicating mechanistic understanding and predictive metabolic modeling across culture scales. To address this challenge, we developed a modular multiscale mechanistic foundation model that links molecular, cellular, and macroscopic processes while accounting for spatial and metabolic heterogeneity. The framework integrates extracellular culture dynamics, intracellular metabolic fluxes, and cellular redox states by extending a previously established monolayer kinetic network and coupling it with a biological systems-of-systems (Bio-SoS) multiscale model for aggregate cultures, incorporating explicit redox interactions. Systematic monolayer and aggregate experiments (including multiple isotopic tracers, extracellular metabolite profiling, and two-photon optical redox imaging) were used to improve and validate the model. This integrated framework unifies heterogeneous datasets across culture configurations and enables mechanistic interpretation of metabolic and redox responses across heterogeneous culture scales, providing a quantitative foundation for scalable iPSC biomanufacturing.

Chemotherapy-induced oral mucositis (CIOM) is a debilitating complication with limited therapeutic options. Mesenchymal stem cells (MSCs) promote tissue repair through paracrine signaling, and stem cell-derived nanovesicles (SC-NVs) have emerged as a scalable, cell-free therapeutic alternative. However, the regenerative potential of SC-NVs has not been investigated in the context of CIOM. This study evaluated the regenerative effects of SC-NVs derived from human adipose-derived MSCs (AD MSCs) in vitro assays and a rat CIOM model. Transcriptomic profiling showed enrichment of wound healing and angiogenesis-related genes in AD MSCs. SC-NVs were produced by serial extrusion and characterized by nanoscale size and reproducible protein content. Following intralesional injection, SC-NVs localized to the ulcer bed and remained detectable for up to 5 days. SC-NV treatment enhanced epithelial regeneration, promoted angiogenesis, and reduced inflammatory markers in vitro and in vivo. These findings support SC-NVs as a scalable, cell-free therapeutic platform for CIOM.

Neural stem cells (NSCs) maintain central nervous system (CNS) homeostasis through self-renewal and differentiation into neurons and glia. Although physical crowding shapes the NSC niche during CNS development, its role in fate determination remains poorly understood. We investigated how NSC crowding influences intercellular junctions and lineage specification in 2D and 3D environments. While crowding promotes neuronal differentiation in both environments, robust junctional remodeling occurred only in 3D. Specifically, 3D crowding uniquely upregulated connexin 43 (Cx43)-mediated gap-junction assembly. Pharmacological Cx43 inhibition selectively attenuated 3D crowding-induced neuronal differentiation, demonstrating that gap-junction signaling is essential for fate determination in 3D. These findings highlight that the regulatory influence of NSC crowding is dimension-dependent and mediated through Cx43 gap-junction communication. By elucidating how biophysical context integrates with intercellular signaling to guide NSC behavior, this study offers mechanistic insights into stem cell biology and informs biomimetic 3D culture systems and regenerative strategies for neural tissue repair.

Postoperative recurrence and metastasis in esophageal squamous cell carcinoma (ESCC) are closely associated with cancer stem cells (CSCs), though the heterogeneity and key molecular mechanisms underlying CSC-driven progression remain incompletely understood. In this study, we identified a malignant, stem-like subpopulation in ESCC using single-cell sequencing data and screened for subpopulation-specific markers via machine learning algorithms, identifying KRT15 as a candidate. Functional experiments in vitro and in vivo demonstrated that the overexpression of KRT15 promoted proliferation, migration, invasion, and stemness in ESCC cells, while its knockdown suppressed these phenotypes. Clinically, high KRT15 expression was significantly associated with poorer overall survival and progression-free survival and served as an independent prognostic risk factor. Collectively, our findings indicate that KRT15 acts as a functional regulator of stemness and invasiveness in ESCC, highlighting its potential as a therapeutic target and a prognostic biomarker for postoperative risk stratification.

Radiation enteritis (RE) is a common complication following radiotherapy, adversely affecting patient prognosis and quality of life. This study aims to analyze the evolving research landscape of RE prevention and management through a data-driven approach, aiming to delineate the developmental trajectory, identify research hotspots and emerging frontiers, and forecast future trends in RE prevention and management.

The survival and function of three-dimensional tissues critically depend on the establishment of a functional vascular network that ensures oxygen and nutrient supply and waste removal. Insufficient vascularization leads to hypoxia, metabolic stress, and cell death, making angiogenesis a fundamental requirement for successful tissue regeneration. This requirement is particularly evident in highly vascularized tissues such as bone, where vascular networks closely regulate tissue metabolism and repair.

Tripartite motif-containing 28 (TRIM28), a transcriptional regulatory factor, is involved in various biological processes. However, its role in early-onset preeclampsia (EOPE) remains unclear. An EOPE mouse model was established using Nω-Nitro-L-arginine methyl ester (L-NAME), while TRIM28 or tumor protein p53 (p53) expression was modulated through lentiviral infections. Maternal blood pressure and urinary protein levels were measured. Placental tissues were collected at embryonic day 17.5 for hematoxylin-eosin staining, immunohistochemistry, Western blot, and real-time quantitative polymerase chain reaction. In vitro, HTR-8/SVneo trophoblast cells were exposed to hydrogen peroxide (H2O2) to simulate oxidative stress. TRIM28 and p53 were overexpressed via lentiviral vectors, and cell apoptosis and molecular changes were assessed. TRIM28 expression was significantly downregulated in placentas from EOPE mice. Mechanistically, TRIM28 suppressed p53 level, downregulating pro-apoptotic proteins Bcl-2-associated X protein (Bax) and cleaved caspase-3, while upregulating the anti-apoptotic protein B-cell lymphoma-2 (Bcl-2). In trophoblast cells, TRIM28 alleviated H2O2-induced apoptosis by promoting p53 ubiquitination and thereby reducing its pro-apoptotic activity. TRIM28 attenuates oxidative stress-induced trophoblast apoptosis and may help protect against the development of EOPE.

Bisphenol A (BPA), a widely encountered environmental endocrine-disrupting chemical, has been linked to an increased risk of congenital heart defects in epidemiological and experimental studies. To investigate its impact in a human-relevant system, we used a human cardiac organoid (hCO) model derived from human Embryonic stem cells (hESCs) and exposed hCOs to BPA concentrations ranging from environmentally relevant to higher experimental levels (0.1-10 μmol/L) throughout differentiation. BPA exposure dose-dependently impaired cardiomyocyte contractility and disrupted endothelial network formation. BPA exposure also induced apoptosis in hCOs. Subsequently, transcriptomic profiling revealed dysregulation of genes associated with cardiac rhythm and developmental signaling in BPA-treated hCOs. A potential molecular sensitivity point for vascular impairment was observed at 0.5 μmol/L BPA. This research provides in vitro evidence that BPA can perturb key processes in early human heart development, highlighting the necessity for further mechanistic and in vivo studies to clarify exposure relevance and its potential implications for fetal heart health.

This study aims to evaluate the effects of hypoxia-conditioned mesenchymal stem cell exosomes (EH-MSCs) on granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-1α (IL-1α) expression in a dihydrotestosterone (DHT)-induced murine model of androgenetic alopecia.

Neuroinflammation plays a fundamental role in several neurodegenerative diseases, including Alzheimer's disease (AD), the leading cause of dementia worldwide. As the main defense response of the central nervous system (CNS), neuroinflammation can be either protective or detrimental depending on the stage of the disease. The pivotal role of neuroinflammation in AD has led to increasing investigations into neuroinflammatory mechanisms, aiming to develop AD-modifying therapies. A significant advance in the field was the emergence of the human induced pluripotent stem cell (hiPSC) model, enabling the study of patient-derived cells. Moreover, the development of hiPSC-derived brain organoids, which mimic specific aspects of the human CNS, has expanded our understanding of neuroinflammation in AD. Here, we review how AD organoid models have evolved, focusing on the integration of microglia-the brain's primary immune surveillance cells. We also summarize recent findings on how glial activation and the crosstalk between microglia and other CNS cells affect AD progression. Lastly, we address the potential of hiPSC-derived organoids as a preclinical model for screening AD drugs.

Rotator cuff repair often results in scar tissue rather than tendon regeneration, leading to inferior strength and high re-tear risk. This study evaluated the regenerative efficacy of an injectable formulation combining adipose-derived stem cell (ADSC) clusters with collagen in an animal model.

Gastrointestinal diseases often involve cellular damage, degeneration or dysfunction in the tract, frequently requiring surgical interventions risking complications and lowered quality of life. Regenerative medicine holds great promise in improving patient care and providing novel treatment options for previously irreparable and untreatable tissues. Despite the clinical potential of intestinal organoids as a resource for regenerative cell therapy and bioengineering, the lack of clinical-grade cultures has hampered further development. Moreover, strategies to efficiently and reliably expand clinical-grade cultures at the scale required for application is limited.

Type 2 diabetes (T2D) and its complications represent a complex disorder involving multiple pathophysiological processes. Although conventional therapeutic approaches partially regulate blood glucose, they fail to fundamentally reverse disease progression or effectively prevent complications. This review summarizes the current research advance and challenges of using different forms of mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) in treating T2D and complications. It begins with an introduction to the characteristics of MSC-EVs. Subsequently, the mechanisms and therapeutic prospects of natural MSC-EVs are analyzed, with a focus on their roles in inflammatory modulation, tissue regeneration, and improving insulin resistance. Engineering MSC-EVs, covering strategies including optimizing MSC culture conditions, modifying EV contents, and establishing MSC-EV delivery systems based on bioactive materials are then discussed, which boost EV yield and quality while enhancing therapeutic efficacy. Current challenges, including the limited yield and high heterogeneity of natural MSC-EVs, as well as issues related to long-term safety, immunocompatibility, and large-scale production of engineered MSC-EVs are finally overviewed, with emphasizing artificial intelligence in guiding future research directions. These summaries are crucial for clinical translation of MSC-EVs and will ultimately provide T2D patients with an effective and safe treatment option.

Osteoporosis (OP) is a metabolic bone disease characterized by low bone mineral density (BMD), and its pathogenesis involves endoplasmic reticulum (ER) stress-related cell death. This study aimed to identify diagnostic biomarkers associated with ER stress-related cell death in OP and explore their underlying mechanisms. The training dataset (GSE56815), validation dataset (GSE56814), and single-cell RNA sequencing (scRNA-seq) dataset (GSE147287) were downloaded. Differentially expressed genes (DEGs) between OP patients and controls were identified. Candidate genes were obtained by intersecting DEGs with ER stress-related genes and programmed cell death (PCD)-related genes. Machine learning was used to screen intersection genes, and biomarkers were determined via expression level analysis. Gene set enrichment analysis (GSEA), immune cell infiltration analysis, drug prediction and molecular docking, scRNA-seq analysis, key cell screening, cell communication analysis, and pseudotime analysis were performed. Finally, reverse transcription quantitative polymerase chain reaction (RT-qPCR) were further conducted. A total of 28 candidate genes were obtained by intersection. CAMKK2 and DAPK3 were confirmed as biomarkers, and were consistently down-regulated in both datasets and verified by RT-qPCR. GSEA analysis revealed that biomarkers were enriched in cytokine-cytokine receptor interaction. Correlations between biomarkers and activated dendritic cells were found via immune cell infiltration analysis. Preliminary computational analyses indicated that drugs including calcitriol and danazol may potentially interact with the biomarkers in a stable manner. Bone marrow-derived mesenchymal stem cells (BM-MSCs) were identified as potential key cells via scRNA-seq analysis. Complex interactions involving BM-MSCs, such as ANGPTL4-CDH11 mediating BM-MSC self-communication, were revealed by cell communication analysis. Dynamic expression of biomarkers during BM-MSC differentiation was shown by pseudotime analysis: CAMKK2 fluctuated with differentiation stages, while DAPK3 shifted from high to low then high expression. CAMKK2 and DAPK3 were confirmed as diagnostic biomarkers for OP, providing insights into OP diagnosis and potential therapeutic targets.

Tissue engineering offers great promise for regenerating damaged organs including the heart. Although direct attachment of grafts at the target site is possible during surgery, minimally invasive delivery and suture-free approaches could reduce patient discomfort and allow repeat administration. However, for the therapy to be effective it is essential that the graft is successfully delivered to the epicardium and retained on target. Here, methacrylated alginate-based shape-memory patches labelled with 111InCl3 and loaded with luciferase expressing stem-cells were either injected towards the epicardium under ultrasound guidance or surgically grafted onto mouse hearts. Patch and cell location were serially tracked using SPECT-CT and bioluminescence imaging. Radiolabelling of shape-memory patches permitted serial tracking of graft location for seven days in-vivo, and revealed that injected patches rarely attached on-target whilst surgically implanted patches rapidly detached from the epicardium. In-vivo imaging was then used to evaluate modifications to biomaterial formulation and patch attachment strategies. This ultimately resulted in effective, suture-free surgical attachment of chitosan-coated patches loaded with luciferase-expressing human embryonic stem cell-derived epicardial cells onto the heart, illustrating a model therapeutic. This translational imaging approach facilitates iterative optimization of a novel biomaterial and could have wide-reaching applications for enhancing a range of regenerative therapies.

Embryonic stem cells (ESCs) constitute a unique lab resource, as they can differentiate to all other cell types, making them pluripotent. We established cynomolgus ESCs using ICSI-derived blastocysts. Cynomolgus ESCs expressed pluripotent markers in immunostaining and fluorescence-activated cell sorting analyses. To investigate its differentiation potential, we confirmed the expression of layer markers from the three germ layers after embryonic body differentiation. Moreover, our ESC shows a normal genotype and no mycoplasma contamination.