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.

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.

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.

Regeneration can rely on multiple cellular sources, including stem cells, self-duplicating cells, and transdifferentiating cells. A central question in regenerative biology is how these distinct lineages contribute to repair and interact within a functionally regenerated tissue. We previously developed the CellCousin system to study cellular plasticity using inducible recombination and nitroreductase-mediated ablation in zebrafish. Here, we present CellCousin2, which introduces two key improvements for the long-term tracking of spared and regenerating cells. First, to reduce background recombination, we developed a Dihydrofolate Reductase (DHFR)-CreER system with dual control: DHFR-mediated degradation in the absence of trimethoprim, and tamoxifen-dependent activation. This combination minimizes leakiness while maintaining high recombination efficiency. Second, we replaced the original nitroreductase with NTR2.0, enabling effective ablation with a tenfold lower metronidazole concentration, reducing off-target effects on the liver. Together, these enhancements make CellCousin2 a robust platform for dissecting the dynamics and interactions of regenerative lineages.

Exosomes, tiny extracellular vesicles (EVs) from different cell types, are gaining attention in dermatology due to their unique properties. They enhance cell communication, transport bioactive substances, and influence immune responses, making them valuable for skin regeneration, wound healing, and addressing skin conditions.

Lysosomal dysfunction is a core pathological driver of neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS). Transcription factor EB (TFEB) serves as a master regulator of lysosomal biogenesis, and its pharmacological activation represents a strategy to restore lysosomal function in disease and aging. Here, using a series of artificial intelligence-powered computational virtual screening workflows, we have identified isoginkgetin (ISO), a small-molecule compound, as a potent TFEB activator that promotes mechanistic target of rapamycin complex 1 (mTORC1)-independent TFEB nuclear translocation to enhance lysosomal biogenesis and function. Mechanistically, ISO functions as an ATP-competitive inhibitor that binds to the key Lys85 residue within the ATP-binding pocket of glycogen synthase kinase 3β (GSK-3β), thereby regulating the GSK-3β-TFEB signaling axis to activate TFEB nuclear translocation. Functionally, ISO improves lysosomal function and protects motor neurons differentiated from induced pluripotent stem cells derived from patients with ALS from degeneration. Collectively, these results support the hypothesis that lysosomal dysfunction is a druggable target for ALS.

Pulmonary fibrosis (PF) is a progressive interstitial lung disease characterized by alveolar epithelial injury, inflammation, and excessive extracellular matrix deposition, yet current therapeutic options remain limited. Panax ginseng C.A. Meyer, a renowned qi-tonifying herb in traditional Chinese medicine, has long been used to enhance spleen and lung function by replenishing qi. However, the mechanism of action of its primary active component, ginseng stem and leaf saponins (GSLS), in pulmonary fibrosis remains incompletely understood.

Acute Myeloid Leukemia (AML) originates from the hematopoietic stem and progenitor cell compartment and is associated with an overall poor clinical outcome. T-cell engaging bispecific antibodies (TCEs), binding to a tumor-associated antigen and to CD3, redirect T-cells to the target-antigen expressing cells in an MHC/TCR-independent fashion. The development of TCEs for clinical application is facing several challenges. Firstly, it is difficult to identify a tumor-selective, non-MHC-presented tumor target, not expressed on the tissue of tumor origin, thus limiting specificity. Secondly, CD3-directed TCEs do not provide a second, T-cell activating signal, such as the stimulation of CD28 or 41BB, thus possibly limiting T-cell efficacy. To address both aspects, we generated a CD33xCD28 IgG4-scFv2 with CD28 agonistic activity and tested it in combination with a previously by us reported CD117xCD3 TCE in AML. Combining these two bispecific antibodies significantly improved T-cell mediated lysis of AML cell lines and primary AML samples by enhancing T-cell activation, proliferation and cytokine release in vitro. Furthermore, the addition of CD33xCD28 IgG4-scFv2 showed faster time to cell attachment, increased lytic events, and improved specificity towards double-target expressing cells. In summary, the data indicate that combining co-stimulation via a second tumor-associated antigen to CD3-TCEs enhances T-cell lytic activity and simultaneously increases specificity against double-target expressing AML cells.

A plant's indeterminate growth requires constant cell proliferation and stem cell maintenance to support its developmental plasticity. The root meristem is an excellent system to study the developmental control of plant cell cycles due to the organ's accessibility and the tight link between cell cycle and developmental regulation. Studies have uncovered diverse pathways that shape root tissue patterning and cell identity, but how these mechanistically connect to cell cycle components remains unclear. Recent work and new approaches are starting to bridge this gap. In this review, we synthesize recent findings on the developmental regulation of cell cycle progression across distinct cell types and developmental zones in the Arabidopsis thaliana root apical meristem, highlighting cells and regions of the root where these processes have been thoroughly studied, and others where we know little. These discoveries reveal a nuanced relationship between cell identity and cell cycle regulation that implies an active role for cell cycle modulation in the patterning and developmental plasticity that are integral to plant growth.

The combination of hypomethylating agents (HMA) and venetoclax (VEN) has transformed acute myeloid leukemia (AML) treatment. Data on donor lymphocyte infusion (DLI) with HMA/VEN for relapse after allogeneic hematopoietic cell transplantation (alloHCT) remain limited. We retrospectively analyzed 78 adults with relapsed myeloid neoplasms after first alloHCT between 2018 and 2025. DLI was given with HMA, HMA/VEN, or other/no treatments. The primary endpoint was event-free survival (EFS), defined as time to death or second alloHCT. Median time to relapse after alloHCT was 12.9 months (range 2.2-192.4). Initial DLI doses ranged from 0.3 to 8.14 × 10⁶ CD3⁺ cells/kg. Median EFS after first DLI was 15.2 months: with 16.2 (DLI/HMA), 14.3 (DLI/HMA/VEN), and 21.1 (DLI/other), respectively. Death occurred in 25.6% and second alloHCT in 32.1% of patients. GvHD of any kind after DLI treatment manifested in 30.8%, both events comparable across groups. Complete remission (CR) after DLI was achieved in 42.3% after a median of 4.2 months, including patients with TP53 mutations (n = 9). Approximately 40% of patients with relapsed myeloid malignancies were successfully salvaged with DLI and combination treatments. Patients with high-risk features such as morphological relapse were overrepresented in the DLI/HMA/VEN cohort but achieved comparable outcomes to the other treatment groups. This finding suggests successful treatment of even morphological relapse by addition of VEN to DLI/HMA regimens while supporting the need for controlled trials.

This study aimed to characterize transcriptional and epigenetic remodeling in the cornea induced by acute inflammation.

ObjectiveTo systematically review and quantitatively synthesize in vivo evidence on extracellular vesicle (EV)-based therapies for regenerative endodontic procedures, focusing on mineralization and angiogenesis outcomes.MethodsWe conducted a systematic review and meta-analysis of in vivo preclinical dentoalveolar/regenerative endodontic models comparing EV-based interventions (exosomes/microvesicles/apoptotic bodies), alone or with scaffolds, versus control conditions. Searches were performed in Web of Science Core Collection and Scopus from inception to 31 December 2025, with reference screening. Random-effects meta-analyses pooled standardized mean differences (SMDs) for mineralization and angiogenesis; heterogeneity was assessed using I2. Risk of bias was evaluated using the Systematic Review Centre for Laboratory animal Experimentation tool.ResultsTwenty-one studies met inclusion criteria; seven were included in the mineralization meta-analysis and five in the angiogenesis meta-analysis. EV-based therapies significantly increased mineralization versus controls (SMD = 6.43; 95% confidence interval (CI) [3.13-9.73]; I2 = 91%) and angiogenesis (SMD = 7.89; 95% CI [3.94-11.85]; I2 = 82%). Subgroup analyses suggested stronger effects for EVs derived from dental pulp stem cells, stem cells from human exfoliated deciduous teeth, and stem cells from apical papilla. Risk of bias was predominantly unclear due to limited reporting of randomization and blinding. Considerable heterogeneity, small numbers of pooled studies, and variability in EV isolation, characterization, dosing, and outcome assessment limit generalizability and translation.ConclusionsEV-based therapies enhance mineralization and angiogenesis in preclinical regenerative endodontic models, with dental stem cell-derived EVs showing the greatest apparent potential. However, effect sizes should be interpreted cautiously given very high heterogeneity and methodological/reporting limitations.PROSPERO registration: Centre for Reviews and Dissemination 420251107328.

Lung organoids are versatile experimental models, but their broader use in studying human disease is limited by the scarcity of starting material and the complexity of current methods. To align organoid technology with common clinical practice, we developed airway and alveolar organoids using cells obtained from patients' bronchoalveolar lavage (BAL) fluid. Building on existing techniques, we showed that BAL is a reliable, accessible source of primary human epithelial cells, yielding airway and alveolar organoids within 10 days. Organoids can then be expanded over many passages for downstream analysis. Our streamlined methods do not require cell sorting or other complex procedures, all cells are derived from a single patient, and media are based on serum-free, chemically-defined formulations. Here, we present detailed protocols for organoid establishment, standardized passaging and phenotyping, and differentiation of both airway and alveolar models. We provide a time course of BAL-derived airway organoid differentiation at air-liquid interface, and we demonstrate proof of principle for differentiation of BAL-derived alveolar organoids in 3D culture. These methods can be readily adapted to generate and characterize organoids from lung tissue, tracheobronchial specimens, or other primary cells from humans or mice, expanding the potential to use lung organoids for disease modeling.

The repair of tumor-induced bone defects requires regenerative materials capable of functioning within the harsh conditions of cancer therapy. Herein, we introduce a biomimetic scaffold designed to simulate the post-chemotherapy tumor microenvironment to investigate its specific effects on tissue regeneration. The scaffold features a PLGA knitted mesh/collagen sponge hybrid loaded with mineralized, DOX-carrying mesoporous silica nanoparticles (DOX-MSNCaP). The sustained release of DOX facilitates potent tumor cell elimination, thereby establishing a residual post-chemotherapy microenvironment. We subsequently explored the biological response of mesenchymal stem cells (MSCs) to this specific biomimetic environment. Our results indicate that the scaffold significantly enhances MSC adhesion and drives osteogenic differentiation through the upregulation of YAP/TAZ signaling. Overall, these findings suggest that following tumor eradication, the scaffold effectively facilitates MSC-mediated osteogenesis, serving as a promising therapeutic strategy for post-tumor bone reconstruction.

Glial cells play a critical role in neural development, function, and immune regulation, with microglia serving as the principal immune cells of the central nervous system and retina. Although microglia are central to neuroinflammation and disease progression, progress in understanding human microglial biology has been limited by the lack of physiologically relevant in vitro models. Stem cell-derived brain and retinal organoids provide three-dimensional systems that recapitulate human tissue architecture and developmental trajectories, offering new opportunities to study neuroimmune interactions. This review summarizes strategies for integrating microglia into neural organoids through co-differentiation and transplantation, and outlines methodologies for establishing humanized immune microenvironments and assessing microglial maturation, migration, phagocytic function, and inflammatory activation. We highlight applications of organoid-microglia models in neurodevelopmental and neurodegenerative disorders, including autism spectrum disorder, Alzheimer's disease, and retinal diseases, as well as their potential in drug screening and microglia-targeted interventions. Additionally, emerging technologies-such as organ-on-a-chip platforms, spatial transcriptomics, and multi-omics analyses-are enhancing the physiological relevance and analytical power of these systems. Overall, organoid-microglia platforms bridge a critical gap between conventional cell culture and in vivo models, enabling deeper insights into neuroimmune interactions and accelerating the development of precise immunomodulatory therapies.

Ovarian cancer remains the most lethal gynecologic malignancy due to strong interpatient heterogeneity and immune evasion. Traditional two-dimensional cultures and animal models lack the ability to maintain interactions among tumors, immune cells, and stromal cells and have limitations in clinical translation. This review discusses the organoid construction methods using adult stem cells (normal epithelium, tumor tissues and ascites), and induced pluripotent stem cells, comparing various culture platforms from air-liquid interface to microfluidic devices. We highlight organoids containing immune components are valuable for assessing T cell exhaustion, NK cell cytotoxicity, and stromal communication, which help to screen immunotherapy, discover biomarker, and profile drug resistance. The persistent challenges include limited vascularization, short-term maintenance of immune components and lack of standard protocols. We present new solutions that integrate multi-omics, biomaterials and automated perfusion to improve physiological fidelity and scalability. Collectively, ovarian cancer organoids with immune microenvironment can bridge preclinical gaps and accelerate the development of personalized immune therapy.