Objective: To investigate the effect and underlying molecular mechanism of interleukin-10 (IL-10) secreted by M2 macrophages on the osteogenic differentiation ability of rat bone marrow mesenchymal stem cells (BMMSCs) after irradiation. Methods: Between February 2024 and April 2025, eight healthy male SD rats aged 2 to 3 weeks were selected, primary BMMSCs and macrophages from SD rats were cultured in vitro. Macrophages were polarized to the M2 phenotype, and their surface markers were identified by flow cytometry and immunofluorescence. The experiment was divided into four groups: normal BMSC control group (CON), 4 Gy irradiation group (4Gy), 4 Gy irradiation+M2 macrophage co-culture group (4Gy+8 μm), and 4 Gy irradiation+M2 macrophage co-culture+IL-10 neutralizing antibody group(4Gy+8 μm+m/r IL-10). An in vitro cellular irradiation model was established by exposing BMMSCs to X-ray radiation at a dose of 4 Gy. A non-contact co-culture system between M2 macrophages and irradiated BMMSCs was established using Transwell chambers with an 8 μm pore size. After 48 hours of co-culture, ELISA was used to detect the IL-10 concentration in the supernatant of each group, and Western blot was used to measure the expression levels of key osteogenic differentiation markers (ALP, RUNX2, OCN) and STAT3 signaling pathway-related proteins (p-STAT3, STAT3) in BMMSCs. The specific role of IL-10 was verified by adding an IL-10 neutralizing antibody. Results: Cell counting kit-8 assay results showed that on day 7 post-irradiation, the absorbance value of the 4 Gy Irradiation group (0.241±0.093) was significantly lower than that of the control group (1.794±0.083) (t=21.63, P<0.001). Western blot analysis indicated that the expression levels of osteogenic markers ALP and RUNX2 in the irradiation group (0.819±0.074, 0.785±0.074) were significantly lower than those in the control group (1.000±0.067, 1.000±0.056) (t=3.16, P=0.034; t=4.01, P=0.016, respectively). Immunofluorescence analysis revealed that the fluorescence intensities of RUNX2 and ALP in the irradiation group (19.932±1.291, 7.316±0.089) were markedly weaker compared to the control group (31.154±3.352, 30.789±1.455). After co-culture with M2 macrophages, the proportion of viable cells in the co-culture group [(77.800±1.758)%] was significantly higher than that in the Irradiation group [(61.933±2.732)%] (P<0.001). Furthermore, the IL-10 concentration in the supernatant of the co-culture group [(46.39±1.879) pg/mL] was significantly higher than that in the irradiation group [(7.530±0.239) pg/mL] (t=36.74, P<0.001). Western blot results demonstrated that the expression levels of ALP, RUNX2, and OCN in the co-culture group (0.879±0.020, 1.045±0.059, 1.173±0.082, respectively) were significantly higher than those in the Irradiation group (0.749±0.031, 0.858±0.050, 0.785±0.073, respectively) (t=8.07, P=0.015; t=5.01, P=0.038; t=3.07, P=0.918, respectively). Adding 1 μg/ml IL-10 neutralizing antibody to the co-culture system significantly reduced the IL-10 level in the supernatant [(6.521±0.460) pg/mL] compared to the co-culture group [(26.270±6.486) pg/mL] (t=5.06, P=0.037). The p-STAT3/STAT3 ratio in the neutralizing antibody group (0.840±0.071) was significantly lower than that in the co-culture group (1.289±0.156) (t=4.27, P=0.051), and the osteogenic differentiation capacity of BMMSCs was also notably attenuated. Conclusions: M2 macrophages can improve the osteogenic differentiation ability of BMMSCs after irradiation damage by secreting IL-10 and activating the STAT3 signaling pathway.

Objective: To explore the regulatory mechanism of transient receptor potential cation channel subfamily M member 2 (TRPM2) on the osteogenic differentiation capacity of bone marrow-derived mesenchymal stem cells (BMSCs), and to clarify the role of TRPM2-regulated mitophagy in the progression of periodontitis. Methods: Twelve TRPM2 gene knockout (TRPM2-/-) mice and twelve wild-type (WT) mice were used in this study. A periodontitis model was established by silk ligation on the maxillary second molars of mice, with sham operation performed in the control group, and the modeling lasted for 10 days. The mice were divided into four groups (n=6 per group): WT sham operation group, WT periodontitis group, TRPM2-/- sham operation group, and TRPM2-/- periodontitis group. In the periodontitis group, silk ligation was performed on the maxillary second molars of mice, while no silk ligation was conducted in the sham operation group. Micro-CT was employed to collect imaging data for three-dimensional reconstruction. CTvox and CTAn v1.15.4.0 software were used to quantify the distance from the cementoenamel junction to the alveolar bone crest (CEJ-ABC) and bone volume fraction (BV/TV) in maxillary bone tissues of the mice in four groups. Statistical analysis was performed subsequently. Immunohistochemical staining was conducted to detect the expression intensity of Runt-related transcription factor 2 (RUNX2) in periodontal tissues in maxillary bone tissues of the mice in four groups. BMSCs were isolated from the femurs of the two types mice and cultured in vitro, followed by induction for osteogenic differentiation. Alizarin red S (ARS) staining and alkaline phosphatase (ALP) staining were used to evaluate the osteogenic differentiation potential of BMSCs. Western blotting (WB) was performed to determine the expression levels of osteogenic-related markers [RUNX2, bone morphogenetic protein 2 (BMP2), ALP, osteopontin (OPN)]. Meanwhile, transmission electron microscopy (TEM) was used to observe intracellular mitophagy status. WB was applied to detect the expression of autophagy-related proteins [Microtubule-associated proteins 1A/1B light chain 3 (LC3), PTEN-induced putative kinase 1 (PINK1), Parkin RBR E3 ubiquitin protein ligase (Parkin)], and immunofluorescence colocalization labeling was used to assess the fluorescence intensity of LC3, Translocase of the outer mitochondrial membrane 20 (Tomm20), and Lysosomal-associated membrane protein (LAMP). Results: No statistically significant differences were observed in bone volume fraction, trabecular number, and trabecular separation between TRPM2-/- and WT mice (all P>0.05). However, the buccal and palatal CEJ-ABC values in the TRPM2-/- periodontitis group [(265.40±21.72) μm and (273.30±17.56) μm, respectively] were significantly lower than those in the WT periodontitis group [(416.50±20.90) μm and (428.00±17.59) μm, respectively] (both P<0.001). In addition, the relative expression level of RUNX2 in periodontal tissues of the TRPM2-/- periodontitis group [(15.03±0.48) %] was significantly higher than that of the WT periodontitis group [(11.95±0.40) %] (P<0.001). In vitro experiments (ALP and ARS staining) demonstrated that the osteogenic differentiation capacity of BMSCs derived from TRPM2-/- mice was significantly enhanced compared with that from WT mice. WB results showed that the expression levels of osteogenic-related markers (RUNX2, BMP2, ALP, OPN) in BMSCs from TRPM2-/- mice were all upregulated compared with WT mice (all P<0.05, respectively), and so as the protein levels of mitophagy-related indicators (LC3 and BECLIN1)(both P<0.001). Furthermore, TRPM2 deficiency remarkably upregulated the expression of proteins related to the PINK1/Parkin pathway (all P<0.001). Conclusions: TRPM2 regulates the osteogenic differentiation capacity of BMSCs through mitophagy, thereby participating in the progression of periodontitis. Therefore, targeting TRPM2 is expected to serve as a novel and effective strategy for the treatment of periodontitis.

Acute graft-versus-host disease (aGVHD) is a common complication of allogeneic hematopoietic stem cell transplantation. The efficacy of standard first-line glucocorticoid treatment is limited; more than 40% of patients develop steroid-refractory aGVHD with an extremely poor prognosis. In recent years, mesenchymal stromal cell (MSC) as a second-line treatment for steroid-refractory aGVHD has been widely studied worldwide. In 2025, the first domestic MSC product was conditional approved by the National Medical Products Administration for steroid-refractory aGVHD in patients aged 14 years and above in China. In light of this, this article reviews the clinical research progress of MSC in the treatment of steroid-refractory aGVHD, focusing on mechanisms and efficacy evaluation, aiming to deepen the understanding of the clinical potential and existing challenges of MSC.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an important treatment option for adult patients with relapsed/refractory acute lymphoblastic leukemia (ALL) , and achieving complete remission (CR) is a critical step before allo-HSCT. Recent studies have shown that immunotherapy with the bispecific T-cell engager (BiTE) blinatumomab can eliminate residual chemotherapy-resistant B-ALL cells, significantly improve remission rates in patients with relapsed/refractory B-ALL and those with positive minimal residual disease (MRD) , successfully bridge patients to allo-HSCT, and provide additional options for post-transplant relapse management and maintenance therapy. This article reviews the application strategies of blinatumomab in adult B-ALL.

This study aimed to explore the application of CAR-T cell therapy bridging to allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with diffuse large B-cell Richter syndrome, and to review recent advances in the diagnosis, pathogenesis, and treatment of this disease. We retrospectively analyzed the diagnosis and treatment course of one patient diagnosed with Richter syndrome at Binzhou Medical University Hospital and reviewed relevant literature. The patient was a 49-year-old female with a history of chronic lymphocytic leukemia (CLL) for over two years, who presented with a progressively enlarging right neck mass, and was ultimately diagnosed with transformation of CLL into diffuse large B-cell lymphoma (DLBCL) , i.e., Richter syndrome. The patient initially achieved a partial response after three cycles of R-DA-EPOCH combined with zanubrutinib therapy. Following disease progression, the treatment regimen was adjusted to a combination of PD-1 monoclonal antibody, CD20 monoclonal antibody, XPO1 inhibitor, and zanubrutinib for one cycle. This was followed by infusion of autologous anti-CD19 CAR-T cells and subsequent bridging to allo-HSCT. Assessments at 3 and 8 months post-transplantation both demonstrated disease complete remission.

Objective: To explore the efficacy and safety of basiliximab for gastrointestinal (GI) chronic graft-versus-host disease (cGVHD) . Methods: This was a retrospective case series. Patients who developed GI-cGVHD after transplantation at the Peking University Institute of Hematology between January 1, 2018, and December 31, 2023, were included. Outcomes included response rate, time to response, overall survival (OS) , and the incidence of neutropenia, anemia, thrombocytopenia, and infections. Results: A total of 41 patients with GI-cGVHD were included, with a median follow-up of 622 (range, 112-2 418) days. All patients received initial therapy including glucocorticoids, calcineurin inhibitors, and/or other immunosuppressive agents (eg, mycophenolate mofetil, mesenchymal stem cells, and sirolimus) . In the basiliximab group (n=25) , baseline diarrhea was grade 2-4 (grade 2, n=4; grade 3, n=18; grade 4, n=3) . Basiliximab was initiated a median of 6 days after initial therapy, and 12 patients (48.0% ) received >4 doses. In the basiliximab group, 22 patients (88.0% ) achieved complete response (CR) . Among patients who achieved CR, 15 (68.2% ) responded within ≤4 doses. In the non-basiliximab group (n=16) , baseline diarrhea was significantly milder than in the basiliximab group (P<0.001) and was grade 1-2 in all patients (grade 1, n=12; grade 2, n=4) . All patients in this group achieved CR. The response rate did not differ significantly between groups (88.0% vs 100.0% , P=0.150) . The 2-year OS rates were 75.4% and 86.7% (P=0.494) , the 2-year cumulative relapse rates were 16.9% and 14.3% (P=0.913) , and the 2-year non-relapse mortality rates were 14.2% and 6.7% (P=0.526) in the basiliximab and non-basiliximab groups, respectively. No new grade 3-4 hepatic or renal dysfunction or cytokine release syndrome was observed in the basiliximab group. In the basiliximab group, neutropenia, anemia, and thrombocytopenia occurred in 24.0% , 28.0% , and 28.0% of patients, respectively. Any infection, viral infection, bacterial infection, and fungal infection occurred in 52.0% , 36.0% , 32.0% , and 4.0% of patients, respectively. Conclusion: Basiliximab may be used to treat GI-cGVHD, with hematologic and infection-related adverse event rates comparable to those of other systemic immunosuppressants. These findings suggest a potential therapeutic option for GI-cGVHD; however, larger prospective studies are needed to further evaluate its safety.

Chronic myelomonocytic leukemia (CMML) is one of myeloid neoplasms originating from hematopoietic stem/progenitor cells, featuring both myelodysplastic and myeloproliferative characteristics. Significant revisions have been made to the diagnostic and classification criteria for CMML in the 5th edition WHO classification (WHO 2022) and the International Consensus Classification (ICC) . Furthermore, besides the previously proposed CMML-specific prognostic scoring system (CPSS) , newer prognostic models such as CPSS-Mol, BLAST, and BLAST-Mol have recently been introduced, incorporating cytogenetic and molecular data. Treatment decisions for CMML patients should be comprehensively determined based on prognostic stratification, considering the patient's symptoms, disease burden (manifested as cytopenias or proliferative features) , evidence of disease progression, as well as individual patient status and preferences. This article provides an overview of diagnostic considerations, prognostic assessment and therapeutic options.

Myelodysplastic neoplasms (MDS) are a group of highly heterogeneous myeloid tumors originating from hematopoietic stem cells, clinically characterized by single or multiple lineage cytopenia with a risk of acute myeloid leukemia transformation. In recent years, significant progress has been made in basic research and the development of novel targeted therapy for MDS, and the 5th edition of the WHO classification has updated the subtypes of MDS. Therefore, the Chinese Society of Hematology, Chinese Medical Association has revised the "Chinese Guidelines for Diagnosis and Treatment of Myelodysplastic Syndromes (2019) " to standardize the diagnosis, differential diagnosis, prognostic assessment, and treatment selection for MDS, thereby better guiding clinical practice.

To summarize the research in tissue regeneration and engineered scaffold materials for the prevention and treatment of lymphedema.

To review the research progress and application prospects of Kartogenin (KGN) in cartilage repair and tissue engineering.

To investigate B1 cell and follicular helper T (Tfh) levels in children with systemic lupus erythematosus (SLE) and to assess whether mesenchymal stem cells (MSCs) regulate peripheral blood B1 cells and Tfh cells in pediatric SLE.

The loss of collagen is one of the core mechanisms of skin aging. Since collagens are among the most abundant proteins in the human body, their dynamic balance is crucial for maintaining the structure and functions of the skin. This paper systematically introduces the functions and action mechanisms of type I, III, IV, VII, and XVII collagens, which play key roles in the process of skin aging. Type I collagen mainly provides mechanical support to the dermis; type III collagen enhances skin elasticity and assists in barrier repair; type IV collagen maintains the stability of the basement membrane; type VII collagen mediates epidermal-dermal anchoring; and type XVII collagen regulates the homeostasis of epidermal stem cells. Furthermore, this paper deeply discusses the research progress in anti-aging strategies based on the mechanism of collagen loss, including the application of antioxidants to reduce oxidative damage to collagen, the use of new active ingredients to stimulate collagen synthesis, and the promotion of endogenous collagen regeneration by supplementing collagen peptides and other methods. This review aims to integrate the functional network of different types of collagens in skin aging, providing new perspectives and ideas for the development of multi-dimensional and synergistic anti-aging strategies.

To explore the mechanisms underlying the therapeutic efficacy of cell transplantation in mouse liver, liquid chromatography-mass spectrometry (LC-MS)-based untargeted metabolomics was employed to screen the differential metabolites in the liver tissue of mice undergoing cell transplantation. We then explored the biological significance of differential metabolites through pathway analysis, correlation analysis, and cluster analysis, aiming to decipher the potential mechanisms affecting the therapeutic outcomes of cell transplantation. The augmenter of liver regeneration (ALR) has been reported to regulate stem/progenitor cell fate. An acute liver failure (ALF) model was induced in mice with carbon tetrachloride (CCl4), and the mice were allocated into three groups (n=5) and transplanted with liver epithelial progenitor cells (LEPCs) with normal expression, overexpression, and knockdown of ALR via splenic injection. Liver tissue samples were collected for LC-MS-based untargeted metabolomics analysis. Differential metabolites were screened and subjected to Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis to identify potential targets influencing the efficacy of cell transplantation. A total of 4 861 metabolites were detected in both positive and negative ion modes. Comparisons were conducted among the three groups with the threshold of fold change (FC)≥2 or≤0.5. The overexpression group and the normal expression group showed minor differences in metabolomic profiles, demonstrating high metabolic similarity. Therefore, we focused on comparing the overexpression group with the knockdown group. Twenty-four differential metabolites were identified between the two groups, with the overexpression group showing 16 upregulated metabolites and 8 downregulated metabolites. Among them, geniposidic acid (GPA) exhibited the most significant upregulation. KEGG pathway enrichment analysis revealed that the overexpression group was primarily associated with six metabolic pathways. Importantly, GPA has been repeatedly reported to participate in the regulation of the bile acid metabolism pathway. ALR overexpression in LEPCs may enhance the therapeutic efficacy by upregulating GPA expression and modulating the bile acid metabolism pathway, thereby creating a favorable liver microenvironment for transplanted cells.

Cell-cultured meat is an innovative type of meat product produced by culturing stem cells in vitro based on the mechanisms of animal growth and repair. It has gradually become an important research focus and development direction in the field of alternative protein foods. Due to the severe lack of historical experience and data regarding human consumption, its safety has attracted global attention. Allergens and allergenicity are one of the core issues, while this field is still in its infancy. In this work, we systematically identify the potential allergen sources throughout the cell-cultured meat production chain, which cover seed cells, production materials (culture media, scaffolds, and carriers), and manufacturing processes. We review recent advances in allergen evaluation and cross-allergenicity research, as well as the key challenges in this emerging field. This study explores the potential for developing a high-throughput, scientifically robust evaluation system for the allergenicity of cultured meat by integrating theories and methodologies from multiple disciplines. The aim is to provide forward-looking and scientific support for the production, risk assessment, and safety management of cell-cultured meat products.

Objective: To evaluate the potential embryonic developmental toxicity of 3, 4-dinitrofurazanfuroxan (DNTF) using embryonic stem cell test (EST) . Methods: In March 2024, the inhibitory effect of DNTF at different concentrations (0, 15.625, 31.250, 62.500, 125.000, 250.000, 500.000, and 1 000.000 μg/ml) on the differentiation of mouse embryonic stem cells (mESCs) into cardiomyocytes, as well as its cytotoxicity to mESCs and 3T3 cells was detected. The known strong embryotoxic drug 5-fluorouracil (5-FU) and non-embryotoxic drug Penicillin-G (P-G) were used to validate the model effectiveness, and the embryotoxicity of DNTF was evaluated. Results: DNTF at concentrations of 31.250 μg/ml and above exhibited an inhibitory effect on mESC differentiation. The proliferation inhibition rates of mESCs and 3T3 cells in the DNTF groups at concentrations of 31.250, 62.500, 125.000, 250.000, 500.000, and 1 000.000 μg/ml were significantly higher than those in the control group (P<0.05). The half-maximal inhibitory concentration (IC(50)) of DNTF for mESC proliferation and differentiation were 633.91 μg/ml and 618.20 μg/ml, respectively. While the IC(50) for 3T3 cell proliferation was 700.84 μg/ml. Based on the validity verification with 5-FU and P-G, DNTF was determined to have no embryonic development toxicity. Conclusion: The EST model indicates that DNTF does not possess embryonic developmental toxicity.

Acute graft-versus-host disease (aGVHD) remains a severe complication following allogeneic hematopoietic stem cell transplantation, and traditional corticosteroid therapy often demonstrates limited efficacy. This review highlights the recent advances in cellular and targeted immunotherapies for aGVHD. Mesenchymal stem cells show considerable efficacy in steroid-resistant aGVHD and are already in clinical use. Regulatory T cells (Treg), including CAR-engineered Tregs, effectively induce immune tolerance and reduce GVHD incidence. Targeted agents, such as CTLA-4 fusion proteins and α4β7 integrin antibodies, mitigate severe aGVHD by blocking immune activation or T-cell homing. Additionally, tissue-repair factors (e.g., IL-22, GLP-2 analogs) and immunomodulatory molecules (e.g., α1-antitrypsin) offer novel strategies that combine tissue protection with immunomodulation. Collectively, these innovative therapies are driving aGVHD treatment toward precision, high efficacy, and low toxicity, demonstrating a promising clinical potential.

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired clonal disorder of hematopoietic stem cells with diverse clinical manifestations, making it susceptible to missed diagnosis or misdiagnosis. Early clinical screening through multidisciplinary collaboration is therefore essential. Treatment strategies should be guided by precise clinical classification. For patients with classic PNH, complement inhibitors are the first-line treatment, whereas for patients with bone marrow failure, the primary treatment should be focused on the underlying bone marrow failure. In cases accompanied by hemolysis, a combination of immunosuppressants and complement inhibitors can be used. During treatment with complement inhibitors, close monitoring of treatment efficacy and complications is required. Based on three representative cases admitted to our hospital, this article highlights the importance of early screening, summarizes key points for standardized diagnosis and treatment of PNH, and provides recommendations for managing breakthrough hemolysis and extravascular hemolysis, with the aim of improving clinical practices.

Radiotherapy is an important treatment modality for tumors and is involved in the treatment course of more than 50% of cancer patients. However, resistance to ionizing radiation results in suboptimal radiotherapy efficacy and contributes to tumor recurrence and metastasis at later stages. With the increasing understanding of tumor pathogenesis, cancer stem cell (CSC), characterized by self-renewal capacity and differentiation potential, have attracted growing attention and play key roles in radiotherapy resistance, tumor progression, metastasis, immune evasion, and other processes. Mechanisms including the tumor microenvironment, DNA damage repair, and epithelial-mesenchymal transition (EMT) are critical drivers of CSC-mediated radiotherapy resistance. Reviewing the key pathways involved and identifying CSC-specific therapeutic targets may provide new insights for developing more efficient and less toxic radiotherapy strategies.

To evaluate the feasibility of using cell membrane vesicles (CMVs) as a delivery system for small interfering RNA (siRNA) and to assess their performance in a lipopolysaccharide (LPS)-induced inflammatory model of human dental pulp stem cells (DPSCs).

To investigate the role of microRNA miR-488-5p, which showed increased expression after the disconnection of the inferior alveolar nerve, in promoting the osteogenic and neurogenic differentiation of rat bone marrow mesenchymal stem cells (rBMSCs), as well as its effect on promoting the neuralized tissue engineered bone regeneration.