Umbilical cord mesenchymal stromal cells (UC-MSCs) are emerging as leading stem cells in regenerative medicine due to their high proliferative capacity, potent immunomodulatory effects, and non-invasive collection. However, the absence of standardized guidance on optimal passage number and tissue-specific characterization criteria limits clinical translation, raising concerns about variability in potency, genomic stability, and safety. This review synthesizes evidence on how in vitro passaging alters UC-MSC properties, including purity, proliferation, senescence, genomic integrity, differentiation, and immunomodulation. Preclinical data suggest that UC-MSCs tolerate extended passaging better than MSCs derived from other sources, with several functional attributes preserved up to later passages. Clinical evidence indicates that early to middle passages (P3-P5) achieve the best balance between scalability and therapeutic efficacy. We further propose an updated immunophenotypic framework incorporating tissue-specific positive and negative markers to enhance clinical-grade characterization. Establishing harmonized passage guidelines and potency assays is essential to maximize reproducibility, safety, and the translational potential of UC-MSC therapies.

SPEECHLESS (SPCH) is the earliest master regulator of the stomatal lineage, and in dicots, defines a transient, self-renewing stem cell state crucial for guard cell formation and environmental plasticity. Over the past decade, studies have revealed how the basic helix-loop-helix transcription factor coordinates a broad transcriptional network controlling cell-cell signaling, asymmetric division, cell-cycle progression, and environmental pathways, while itself subject to multilayered transcriptional and phospho-regulatory controls. These findings position SPCH as a model for understanding how master transcription factors orchestrate lineage progression and integrate intrinsic and environmental cues. Here, we synthesize recent advances in SPCH-mediated gene networks and the regulation of SPCH in the model plant Arabidopsis thaliana, highlighting how this single transcription factor establishes and shapes the stomatal stem cell state, with implications for plant adaptation and crop improvement.

Culture protocols need to yield 100 million equine synovial fluid (SF)-derived mesenchymal stromal cells (SF-MSCs) in around 3 weeks are needed, before these cells can be evaluated as agents of articular repair in clinical trials.

Glioblastoma (GBM) is the deadliest primary brain tumor in adults, where current therapies fail to extend survival meaningfully. Available animal GBM tumor models, especially therapy-resistant and recurrent models with human tumor and human immune cell interactions, are limited, impeding innovative treatment research. To address this critical obstacle, we established a unique GBM mouse model using patient-derived xenografts (PDXs) in humanized mice.

The contribution of microRNAs (miRNAs) to the endothelial differentiation of stem cells from human exfoliated deciduous teeth (SHED) remains largely unclear. This study sought to uncover novel miRNAs implicated in this process. SHED were obtained from deciduous teeth and verified via flow cytometric profiling of CD34, CD90, and CD105. Cells were induced toward endothelial lineage and subjected to miRNA sequencing at 0, 7, and 14 d. Differentially expressed miRNAs were validated by quantitative Polymerase Chain Reaction (qPCR). The influence of miR-3614-5p on endothelial differentiation was examined using qPCR, Western blotting, immunofluorescence, and angiogenesis assays. Direct targeting of lysophosphatidic acid receptor 2 (LPAR2) was tested through luciferase reporter assays, and rescue experiments were performed by LPAR2 overexpression. Results showed that SHED expressed CD34 (19.5%), CD90 (99.1%), and CD105 (92.5%), confirming effective isolation. Sequencing identified 9 consistently downregulated and 11 consistently upregulated miRNAs at both days 7 and 14, with miR-3614-5p denoting stable upregulation and qPCR confirmation. Functionally, miR-3614-5p exerted opposing effects: its overexpression suppressed von Willebrand factor and CD31 expression and impaired tube formation, whereas its inhibition enhanced marker expression and angiogenesis. Mechanistically, LPAR2 was validated as a direct target of miR-3614-5p. Importantly, LPAR2 overexpression reversed the inhibitory effects of miR-3614-5p on endothelial differentiation and angiogenesis. Together, these findings indicated that miR-3614-5p negatively regulates SHED endothelial differentiation and angiogenesis by directly targeting LPAR2, highlighting its potential role as a molecular regulator in this process.

Spinal cord injury (SCI) represents a devastating neurological condition characterized by immediate mechanical damage followed by secondary pathological processes, including acute and chronic inflammation, which exacerbate neuronal loss, axonal degeneration, and glial scar formation, ultimately leading to permanent functional deficits. Emerging research highlights the dual nature of inflammation, where timely modulation can shift from a detrimental M1-like phenotype to a regenerative M2-like state, thereby fostering neural stem cell (NSC) survival and neurogenesis. Strategies for reprogramming inflammation include pharmacological interventions like minocycline or resolvins to dampen excessive cytokine storms, biomaterial scaffolds impregnated with anti-inflammatory agents to create supportive niches, and gene therapies targeting NF-κB pathways to promote anti-inflammatory signaling. Additionally, stem cell-based approaches, such as mesenchymal stem cell transplantation, secrete immunomodulatory factors that enhance NSC migration and remyelination while reducing astrogliosis. Preclinical models demonstrate that these reprogramming tactics not only mitigate secondary injury but also amplify NSC-mediated repair, improving motor recovery and sensory function. Clinical translation faces challenges like timing of intervention and personalized immunomodulation, yet holds promise for novel therapeutics. The objective of this review is to synthesize current evidence on reprogramming inflammatory pathways to optimize NSC function in SCI and to propose integrated strategies for advancing regenerative therapies.

Ribosome collisions act as molecular sensors of cellular stress, yet their role in disease physiology remains unclear. Here, we demonstrate that inhibition of the oncogenic kinase BCR::ABL1 in chronic myeloid leukemia (CML) cells induces ribosome collisions and activates the ribotoxic stress response (RSR). Clinical analyses revealed that CML progression from the chronic phase to the aggressive blast phase correlated with elevated expression of the RSR-initiating kinase ZAK. Although ZAK sustained CML cell proliferation by promoting AKT activity, loss of ZAK function paradoxically reduced the cytotoxic effects of BCR::ABL1 inhibitors. Mechanistically, BCR::ABL1 inhibition promoted phosphorylation of eukaryotic translation elongation factor 2 (EEF2) via the mTOR-EEF2K pathway, slowed translation elongation, and generated nuclease-resistant collided ribosomes that triggered ZAK-dependent p38 activation and apoptosis. Furthermore, pharmacological modulation of translation flux fine-tuned the efficacy of BCR::ABL1 inhibitors, including in primary patient cells. These findings define a ribosome-based stress pathway crucial for CML apoptosis and highlight ZAK-dependent RSR as a therapeutic vulnerability.

Chronic viral infections and cancer challenge immune control by enforcing sustained antigen exposure, which profoundly alters the fate and function of CD8+ T cells. In contrast to acute infections, which induce robust effector differentiation and durable immune memory, persistent infections and tumors drive CD8+ T cells into distinct states of functional adaptation. The best studied chronic adaptation is T cell exhaustion, which is characterized by impaired effector functions, reduced proliferative capacity, sustained expression of inhibitory receptors, and stable transcriptional and epigenetic reprogramming. T cell exhaustion is not a uniform or terminal condition but comprises heterogeneous and dynamic cellular states, including stem-like/precursor populations that retain self-renewal capacity and therapeutic responsiveness. These insights have reshaped our understanding of immune regulation in chronic disease and underpin the success of immune checkpoint blockade therapies. However, heterogeneous and often transient clinical responses highlight critical gaps in our mechanistic understanding of exhausted T cell biology. This review synthesizes recent advances in the cellular and molecular profiling of chronically stimulated CD8+ T cells across chronic viral infection and cancer, focusing on regulatory networks, defining factors, and tissue-specific cues that govern functional adaptation and exploring emerging therapeutic reprogramming strategies.

The role of phosphatidylcholine transporters such as Stard7 in intestinal cancer development is unknown. To explore this issue, we generated a mouse model lacking Stard7 in intestinal epithelial cells (IECs). Loss of Stard7 impaired mitochondrial Complex I activity, led to a severe metabolic and lipid reprogramming, enhanced mitochondrial ROS production and potentiated an mTORC1/ATF4 signature. As a result, levels of enzymes involved in serine biosynthesis were enhanced in Stard7-deficient IECs. We next assessed the consequences of Stard7 deficiency in both Wnt-dependent tumor initiation and in inflammation-driven tumor development. Strikingly, despite generating similar molecular signatures, Stard7 deficiency inhibited tumor development in Azoxymethane (AOM)/Dextran Sulfate Sodium (DSS)-treated mice but promoted Wnt-driven cancer initiation in the intestine. Apc+/Min mice lacking Stard7 in IECs developed more tumors in the distal colon as well as a specific microbiota signature. Collectively, our results suggest that the genetic status critically controls the effects of Stard7 deficiency on intestinal tumor development.

Hyperglycemia is known to worsen lipopolysaccharide (LPS)-induced inflammatory osteolysis. However, regenerative therapy with human umbilical cord mesenchymal stem cells conditioned medium (HUCMSCs-CM) and Tetragonula biroi propolis nanoemulsion (PNE) may suppress inflammatory osteolysis with hyperglycemia. This study investigated how HUCMSCs-CM and PNE affected the osteoblastogenesis markers in rats with hyperglycemia and inflammatory osteolysis. Twenty-eight healthy male rats (1–2 months old) were divided into seven groups: NC (negative control), LP (100 µL LPS), HG (> 230 mg/dL), LH (100 µL LPS with hyperglycemia), LHH (LPS, hyperglycemia, and 100 µL HUCMSCs-CM), LHN (LPS, hyperglycemia, and 100 µL PNE), and LHHN (LPS, hyperglycemia), and 100 µL LPS from Escherichia coli was used to induce calvarial osteolysis. PNE and HUCMSCs-CM were prepared and administered subcutaneously into the calvaria. Thereafter, hyperglycemia was induced via intraperitoneal administration of 30 mg/kg of streptozotocin for 1 week. The rats were sacrificed on day 8, and ELISA was used to measure Coll1a1, ALP, and osteopontin in the blood samples. Immunohistochemistry was employed to examine the osteoblastogenesis markers; RUNX-2, osterix, osteonectin, and osteocalcin. In the LPS-induced inflammatory osteolysis model with hyperglycemia, administration of HUCMSCs and PNE significantly increased osteoblastogenesis markers (P ≤ 0.05). The combination treatment showed the most pronounced effect, enhancing serum Coll1a1, ALP, and osteopontin levels, as well as RUNX-2, osterix, osteonectin, and osteocalcin expression. These findings indicate that HUCMSCs-CM and PNE synergistically promote osteoblastogenesis in hyperglycemia-aggravated inflammatory osteolysis and may represent a promising regenerative therapeutic strategy for inflammatory bone loss under compromised metabolic conditions.

ABCA7 (ATP binding cassette subfamily A member 7) encodes a lipid transporter associated with increasing risk for Alzheimer's disease (AD). A 44-base pair deletion in ABCA7 (rs142076058; p.Arg578Alafs) is a strong risk factor in individuals of African ancestry (AA). However, the biological consequences of this deletion are poorly understood.

Gastric cancer (GC) remains a leading cause of global cancer mortality, necessitating deeper molecular insights. This study identifies KIF15 as a key driver of GC progression through integrated analysis of TCGA data and experimental validation. KIF15 is significantly overexpressed in GC tissues and correlates with advanced tumor stage, metastasis, and poor prognosis. Functional assays demonstrate that KIF15 enhances cancer stem cell (CSC) properties, proliferation, migration, invasion, and cisplatin resistance in GC cells. Mechanistically, KIF15 interacts with peroxiredoxin 1 (PRDX1), stabilizing this antioxidant protein to reduce intracellular hydroperoxides and maintain mitochondrial function. Depletion of PRDX1 reverses KIF15-mediated oncogenic effects. Further investigation reveals Yin Yang 1 (YY1) as the upstream transcriptional activator of KIF15. YY1 directly binds the KIF15 promoter, and its overexpression elevates KIF15 expression. Rescue experiments confirm that YY1 promotes GC malignancy via the KIF15-PRDX1 axis. Crucially, YY1 also transcriptionally regulates PRDX1, forming a coordinated regulatory circuit. In vivo models corroborate that the YY1/KIF15/PRDX1 axis drives tumor growth, metastasis, and chemoresistance. Collectively, these findings establish a novel YY1-KIF15-PRDX1 signaling axis that induces mitochondrial ROS imbalance to facilitate GC progression, offering potential prognostic markers and therapeutic targets.

Previous studies have suggested that intensive chemotherapy to induce bone marrow hypoplasia before allogeneic hematopoietic stem cell transplantation (HSCT) may improve outcomes in relapsed/refractory acute lymphoblastic leukemia. In this retrospective single-center study, we analyzed 14 patients who received clofarabine (CLO) as a preconditioning intervention (PCI) before HSCT between 2019 and 2024. PCI was defined as initiation of conditioning within 2 weeks after CLO. The median age was 34 years, and seven patients were not in remission at the time of CLO. CLO (30 mg/m2 for 5 days) was given in one or two cycles. WBC and bone marrow nucleated cells significantly decreased after CLO. The 1-year overall survival, relapse incidence, and non-relapse mortality rates were 67.5%, 32.2%, and 21.6%, respectively. Neutrophil engraftment was achieved in all patients. Acute and chronic graft-versus-host disease occurred in four and two patients, respectively. Bloodstream infections within 100 days after HSCT were observed in nine patients. Thrombotic microangiopathy (n = 2), sinusoidal obstruction syndrome/veno-occlusive disease (n = 2), drug-induced cardiomyopathy (n = 1), and organizing pneumonia (n = 1) were also observed but were clinically manageable. Considering the high-risk nature of this cohort, CLO-based PCI followed by HSCT appears to be a feasible treatment strategy with acceptable toxicity, warranting further investigation.

Cellular senescence compromises pulp vitality and may negatively affect vital pulp therapy and regenerative endodontics. Exposure to dental materials may accelerate this process, highlighting the need for safer biomaterials and novel therapeutic strategies.

Orally derived mesenchymal stem cells (OMSCs) are an emerging source of cells for treating vascular diseases (VDs). In this systematic review and meta-analysis, for the first time, we reviewed the published preclinical studies that examined the potential of OMSCs and their secretome in treating VDs, focusing on their efficacy and therapeutic mechanism. We electronically searched PubMed, Embase, and Web of Science, from the inception of the databases to December 31, 2024, for relevant literature from peer-reviewed journals. The studies focused on treating VDs in animal models using the OMSC-based strategy were included in the review. The articles were classified by disease, injury model, and outcome. A meta-analysis of the OMSC treatment effects on the cerebral ischemia (CI) infarct volume was conducted using random-effects and fixed-effects models. Forty-one studies were included and classified by type: CI, hypoxic-ischemic encephalopathy (HIE), myocardial ischemia (MI), hindlimb ischemia (HI), and others. Each study presented varying degrees of evidence that OMSCs had positive biological and functional effects on the treatment outcomes of VDs, mainly via paracrine effects. Pooled analysis showed that the effect of OMSC treatment compared with control on infarct volume was − 2.19 (95% confidence interval: − 3.01, − 1.37, p < 0.01) with the random-effects model and − 1.87 (95% confidence interval: − 2.44, − 1.29, p < 0.01) with the fixed-effects model. These results showed that OMSCs can significantly reduce the infarct volume in animal models of CI. Overall, OMSCs show promising potential for treating VDs mainly because of their secretome. However, before moving on to clinical trials, more high-quality preclinical studies with detailed analyses of possible off-target effects are needed.