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18 August 2025, Volume 29 Issue 23 Previous Issue   

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Fe3O4@ZIF-8 nanoparticles affect osteogenic differentiation of bone marrow mesenchymal stem cells under magnetic stimulation Chen Pinrui, Xue Yiyuan, Pei Xibo 2025, 29 (23):  4841-4850.  doi: 10.12307/2025.091 Abstract ( 174 )   PDF (2991KB) ( 142 )   Save BACKGROUND: Bone marrow mesenchymal stem cells play a pivotal role in tissue engineering and bone regeneration. However, promoting the osteogenic differentiation of bone marrow mesenchymal stem cells poses a significant challenge.   OBJECTIVE: To examine the influence of Fe3O4@ZIF-8 nanoparticles on the osteogenic differentiation of bone marrow mesenchymal stem cells under magnetic stimulation. METHODS: Zeolite imidazolate skeleton (ZIF-8) was synthesized by hydrothermal method, and magnetic Fe3O4@ZIF-8 nanoparticles were synthesized by one-pot method (2.5, 5, 10, and 20 µg Fe3O4 were added to the preparation materials, respectively). The Fe3O4@ZIF-8 nanoparticles were characterized by scanning electron microscopy, X-ray photoelectron spectroscopy, X-ray diffraction, and vibration sample magnetometer detection, and suitable materials were selected for subsequent experiments. Bone marrow mesenchymal stem cells of 4-week-old SD rats were extracted and co-cultured with Fe3O4@ZIF-8 nanoparticle solution with different mass concentrations (25, 50, 75, 100, and 125 μg/mL), respectively. Cell proliferation was detected by CCK-8 assay, and the optimal material solution mass concentration was selected. After the mass concentration of the material solution was screened, magnetic stimulation was applied (magnetic field intensity was 0, 50, 100, and 150 MT, respectively). Cell proliferation was detected by CCK-8 assay, and the best magnetic field intensity and Fe3O4@ZIF-8 nanoparticles were selected for the experiment of induced differentiation of bone marrow mesenchymal stem cells. SD rat bone marrow mesenchymal stem cells were co-cultured with ZIF-8, Fe3O4@ZIF-8, and Fe3O4@ZIF-8 (magnetic field intervention) nanoparticle solution, respectively. The single cultured cells were used as blank controls. Lipid induction was followed by oil red O staining. After osteogenesis induction, alkaline phosphatase, alizarin red staining and Runx2 protein concentration were detected.  RESULTS AND CONCLUSION: (1) Under scanning electron microscopy, Fe3O4@ZIF-8 nanoparticles showed a dodecahedral structure. With the increase of Fe3O4 content in the material, the particle size of the nanoparticles increased. Fe3O4@ZIF-8 nanoparticles (5 and 10 µg Fe3O4 was added to the material preparation) with a particle size of about 250 nm (stable functional and biosafety of nanoparticles at this particle size) were selected. (2) The results of CCK-8 assay showed that 50 μg/mL Fe3O4@ZIF-8 nanoparticles (with 10 µg Fe3O4 added to the preparation of the material) could significantly promote the proliferation of bone marrow mesenchymal stem cells under a 100 MT magnetic field. The nanoparticles under this condition were selected for the osteogenic induction differentiation experiment of bone marrow mesenchymal stem cells. (3) After osteogenic induction, the alkaline phosphatase activity, extracellular matrix mineralization degree, and Runx2 protein mass concentration of bone marrow mesenchymal stem cells in Fe3O4@ZIF-8 (magnetic field intervention) group were higher than those in other three groups (P < 0.05). After adipogenic induction, the lipid droplet formation of bone marrow mesenchymal stem cells in Fe3O4@ZIF-8 (magnetic field intervention) group was lower than that in the other three groups (P < 0.05). (4) The results show that Fe3O4@ZIF-8 nanoparticles can promote osteogenic differentiation of bone marrow mesenchymal stem cells under specific magnetic field conditions. Figures and Tables | References | Related Articles | Metrics

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Rabbit bone marrow mesenchymal stem cells transfected with recombinant lentivirus and decalcified bone matrix to construct transgenic tissue engineering materials Ning Yinkuan, Liu Linzhi, Zhou Cila, Long Yubin 2025, 29 (23):  4851-4858.  doi: 10.12307/2025.501 Abstract ( 104 )   PDF (2354KB) ( 102 )   Save BACKGROUND: The use of autologous or allogeneic transplantation materials for tissue repair and reconstruction is limited and carries limitations in clinical applications. Transgenic stem cells and tissue engineering materials offer new therapeutic possibilities. OBJECTIVE: To investigate the in vitro biological characteristics of enhanced green fluorescent protein recombinant lentivirus transfected into rabbit bone marrow mesenchymal stem cells and the biommineralization characteristics of transgenic tissue engineering materials constructed using decalcified bone matrix.  METHODS: Rabbit bone marrow mesenchymal stem cells were obtained through adherent culture and density gradient centrifugation. The fifth-generation bone marrow mesenchymal stem cells were transfected with enhanced green fluorescent protein recombinant lentivirus at the optimal multiplicity of infection (MOI=100). The differences in cell proliferation capacity, cell phenotype, cell cycle, alkaline phosphatase expression, osteogenic transcription factor (Runx2) expression, and osteocalcin gene expression after osteogenesis were observed between the transfected cells and non-transfected cells in vitro. The micromorphology and elemental energy spectrum analysis of the transgenic tissue engineering materials constructed from cells and decalcified bone matrix scaffold were also observed.  RESULTS AND CONCLUSION: Bone marrow mesenchymal stem cells transfected with enhanced green fluorescent protein recombinant lentivirus showed that cell proliferation at 24 and 48 hours after transfection was slower than that of untransfected cells (P < 0.05). After 72 hours, the cell phenotype remained unchanged, and the expressions of alkaline phosphatase, Runx2, and osteocalcin after osteogenic induction were not significantly different from those of untransfected bone marrow mesenchymal stem cells (P > 0.05). The transgenic tissue engineering materials constructed in vitro using enhanced green fluorescent protein recombinant lentivirus transfected bone marrow mesenchymal stem cells and decalcified bone matrix showed good biocompatibility on the decalcified bone matrix scaffold. Based on fluorescence expression intensity, it was estimated that the target gene would exert its maximum biological function in about 2 weeks, and calcium phosphate deposits would continue to appear, demonstrating superior biomineralization characteristics.  Figures and Tables | References | Related Articles | Metrics

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Inhibitory effect of angiotensin II on the brown fat differentiation of rat bone marrow mesenchymal stem cells Liu Chenyang, Wang Jin, Zhang Wenting, Wang Liqing, Yin Xiaoxiao, Zhao Junnan, Jiao Xiangying 2025, 29 (23):  4859-4867.  doi: 10.12307/2025.083 Abstract ( 99 )   PDF (2411KB) ( 119 )   Save BACKGROUND: Bone marrow mesenchymal stem cells are one of the sources of adipocytes and express all renin-angiotensin system components, but the effect of angiotensin II on bone marrow mesenchymal stem cell differentiation into brown adipose tissue is not clear. OBJECTIVE: To observe the effect of angiotensin II on bone marrow mesenchymal stem cell differentiation into brown adipose tissue and investigate the role of angiotensin 1a receptor knockout in effect of angiotensin II on bone marrow mesenchymal stem cell differentiation into brown adipocytes and its potential mechanisms.  METHODS: After isolation and culture of bone marrow mesenchymal stem cells in wild-type and angiotensin 1a receptor knockout SD rats, the cells were cultured to the third generation and randomly divided into four groups: wild type group, knockout group, wild type + angiotensin II group, and knockout + angiotensin II group. The differentiation was induced in the brown fat induced differentiation medium for 14 days. Angiotensin II (100 nmol/L) was added for intervention when the differentiation medium was changed each time in the latter two groups. Western blot assay, qRT-PCR, immunofluorescence, and other methods were used to detect the expression of induced differentiation, lipolysis, β oxidation, and mitochondrial biogenesis in brown fat. RESULTS AND CONCLUSION: Angiotensin II could inhibit the browning of rat bone marrow mesenchymal stem cells. Knockout of angiotensin 1a receptor could improve the inhibitory effect of angiotensin II on brown lipid formation of rat bone marrow mesenchymal stem cells by promoting lipolysis, enhancing fatty acid β oxidation, promoting mitochondrial biogenesis, and enhancing mitochondrial function. These findings provide new research directions and potential therapeutic targets for obesity treatment, revealing the important role of renin angiotensin systems in fat metabolism and its potential as a therapeutic target. 中国组织工程研究杂志出版内容重点：干细胞；骨髓干细胞；造血干细胞；脂肪干细胞；肿瘤干细胞；胚胎干细胞；脐带脐血干细胞；干细胞诱导；干细胞分化；组织工程 Figures and Tables | References | Related Articles | Metrics

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Bone marrow mesenchymal stem cell transplantation for myocardial infarction in rats: effects of acute and chronic exercises Feng Qiang, Pi Yihua, Huang Huasheng, Huang Delun, Zhang Yan 2025, 29 (23):  4868-4877.  doi: 10.12307/2025.087 Abstract ( 86 )   PDF (2376KB) ( 142 )   Save BACKGROUND: Stem cell transplantation has a promising therapeutic prospect in the treatment of myocardial infarction, but the efficacy of stem cell transplantation is limited by the low homing efficiency of transplanted cells to the heart and the low retention rate and survival rate in the heart. Exercise therapy is an important integral component of cardiac rehabilitation for patients with myocardial infarction. However, the role of exercise in stem cell therapy for myocardial infarction has not yet been clarified.  OBJECTIVE: To investigate the effect of exercise (including acute exercise and chronic exercise) on bone marrow mesenchymal stem cell transplantation in rats with myocardial infarction. METHODS: Eighty female SD rats were randomly divided into sham operation group, model group, transplantation group or combination group with random number table method (n=20). Myocardial infarction model of rats in model group, transplantation group, or combination group was made by coronary artery ligation. 24 hours after the model was made, the combination group underwent aerobic exercise for 8 weeks (chronic exercise, 30 min/d, 5 days per week), and within 5 minutes after the first exercise (acute exercise). SD rat bone marrow mesenchymal stem cells labeled with green fluorescent protein were injected into the tail vein of the transplantation group and the combination group. A part of animals from each group were taken 24 hours after the first exercise. The survival rate of stem cells transplanted into rat myocardium, sex-determining region of Y, protein expression of homing factors, oxidative stress, and inflammatory response parameters were measured. After 72 hours of the last exercise, the remaining rats were taken to detect cardiac structure and function, myocardial histological changes, and the number of Ki67+ cells. RESULTS AND CONCLUSION: (1) After acute exercise: Compared with sham operation group, myocardial reactive oxygen species level, malondialdehyde content, tumor necrosis factor-α, and interleukin-1β protein expression increased (P < 0.05), and superoxide dismutase activity decreased (P < 0.05) in model group. Compared with model group, reactive oxygen species, malondialdehyde content, tumor necrosis factor-α, and interleukin-1β protein expression reduced (P < 0.05), superoxidation dismutase activity, stromal cell-derived factor 1α, and CXC chemokine receptor 4 protein expression increased (P < 0.05) in transplantation and combination groups. Compared with the transplantation group, reactive oxygen species, malondialdehyde content, tumor necrosis factor-α, and interleukin-1β protein expression decreased (P < 0.05), stem cell survival rate, sex-determining region of Y mRNA expression, superoxide dismutase activity, stromal cell-derived factor 1α, and CXC chemokine receptor 4 protein expression increased (P < 0.05) in combination group. (2) After chronic exercise: Compared with sham operation group, cardiomyocyte cross-sectional area and collagen content increased (P < 0.05), left ventricular ejection fraction and left ventricular short-axis shortening rate decreased (P < 0.05) in model group. Compared with model group, cardiomyocyte cross-sectional area and collagen content decreased (P < 0.05), Ki67+ cells increased (P < 0.05) in transplantation group. Compared with transplantation group, collagen content decreased (P < 0.05), cardiomyocyte cross-sectional area, left ventricular ejection fraction, left ventricular short-axis shortening rate, and Ki67+ cells increased (P < 0.05) in the combination group. (3) Acute exercise improves the survival rate of exogenous stem cells by promoting stem cell homing and improving myocardial microenvironment, while chronic exercise can stimulate cardiomyocyte proliferation, inhibit cardiac remodeling, and enhance cardiac function after stem cell transplantation. Therefore, exercise can help to optimize the efficacy of stem cell transplantation after myocardial infarction in rats. Figures and Tables | References | Related Articles | Metrics

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Interleukin-10 engineered human umbilical cord mesenchymal stem cells for superior treatment of inflammatory bowel disease Feng Yirui, Gao Tianyun, Wang Yaping, Huang Yahong, Wang Bin 2025, 29 (23):  4878-4887.  doi: 10.12307/2025.512 Abstract ( 102 )   PDF (3792KB) ( 137 )   Save BACKGROUND: Mesenchymal stem cells have been widely used in the treatment of various diseases due to their wide range of sources, their ease of proliferation in vitro and their ability to secrete a range of immunomodulatory factors to suppress inflammation and promote tissue repair and regeneration. However, in the treatment of many diseases, the therapeutic effect is limited. The effort to engineer and modify mesenchymal stem cells for specific disease pathogenesis or intervention targets is an important development for cell therapy in the future. OBJECTIVE: Interleukin-10 is a typical anti-inflammatory cytokine that helps to modulate the immune response and induces macrophage polarization towards an anti-inflammatory phenotype. This study investigated the therapeutic effect of interleukin-10 engineered human umbilical cord mesenchymal stem cells on inflammatory bowel disease. METHODS: Human umbilical cord mesenchymal stem cells stably overexpressing interleukin-10 were established by electro-transfection, and screened for clinical-grade cells based on the cell therapy product criteria. C57BL/6J mice were given 5% aqueous dextran sulfate sodium ad libitum to establish a model of acute colitis. Empty plasmid-transfected human umbilical cord mesenchymal stem cells or interleukin-10-human umbilical cord mesenchymal stem cells (1×106 cells/each mouse) were injected on day 1 before modeling (tail vein injection) and day 4 (intraperitoneal injection) after modeling, respectively. On day 6 after modeling, colon tissue sections were taken for hematoxylin-eosin staining to assess histological changes. Immunofluorescence staining was performed to detect the expression of proliferating cell nuclear antigen and CD31.  RESULTS AND CONCLUSION: The engineered human umbilical cord mesenchymal stem cells stably overexpressing interleukin-10 were constructed, and met the quality standard of clinical-grade human umbilical cord mesenchymal stem cells. Human umbilical cord mesenchymal stem cells could repair acute colitis in mice. The therapeutic effect of interleukin-10-human umbilical cord mesenchymal stem cells was more efficacious, which more significantly suppressed body weight loss (P < 0.05), colon shortening (P < 0.05), and damage of colonic tissues (P < 0.05) in acute colitis mice. In interleukin-10-human umbilical cord mesenchymal stem cell treatment group, there were significantly more proliferating cell nuclear antigen-positive cells and CD31-positive cells in the colon sections than in the human umbilical cord mesenchymal stem cell treatment group, suggesting that interleukin-10-overexpressing human umbilical cord mesenchymal stem cells contributed to the repair of colon tissue by significantly promoting the proliferation of intestinal tissues and angiogenesis. Figures and Tables | References | Related Articles | Metrics

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Action mechanism by which gambogic acid down-regulates expression of protein C receptor to kill triple negative breast cancer stem cells Li Su, Wang Qinghua, Da Mengting, Yang Rui, Chen Daozhen 2025, 29 (23):  4888-4898.  doi: 10.12307/2025.089 Abstract ( 75 )   PDF (3849KB) ( 180 )   Save BACKGROUND: Gambogic acid is highly cytotoxic to breast cancer and can effectively kill triple negative breast cancer stem cells, but the underlying mechanism is still unclear. OBJECTIVE: To investigate the lethal effect of gambogic acid on triple negative breast cancer stem cells as well as the possible mechanisms.  METHODS: PharmMapper database was used to predict the target protein of gambogic acid. String website was used to construct the protein interaction network of various drug targets. Active ingredient-target network was constructed by Cytoscape software. KEGG signal pathway enrichment analysis was performed on potential targets by R language software. The effect of different concentrations of gambogic acid on the activity of human breast cancer cell line MDA-MB-231 was detected by CCK-8 assay. The appropriate concentration was screened. MDA-MB-231 stem cells were enriched by cell ball culture method and treated with gambogic acid at different concentrations (0, 0.5, 1.0, and 2.0 μmol/L) for 24 hours. TUNEL fluorescence staining and flow cytometry were used to detect apoptosis of stem cells. qPCR and western blot assay were used to detect protein C receptor expression. The expression levels of p-PI3K, p-AKT, Caspase-3, and cleaved Caspase-3 were detected by western blot assay. Stem cells were cultured in four groups: Blank control group (stem cells were not treated), siRNA-NC group, siRNA-protein C receptor group, and siRNA-protein C receptor + PI3K agonist group. After culture for 36 hours, the expression levels of p-PI3K, p-AKT, Caspase-3, and cleaved Caspase-3 were detected by western blot assay. RESULTS AND CONCLUSION: (1) Network pharmacology exhibited that the protein C receptor, a marker of triple negative breast cancer stem cells, was one of the targets of gambogic acid. KEGG enrichment analysis involved apoptosis, epithelial growth factor receptor, RAS, and PI3K-AKT signaling pathways. (2) CCK-8 assay results showed that gambogic acid could inhibit the viability of MDA-MB-231 cells, and the median inhibitory concentration IC50 value was (1.18±0.34) μmol/L, so the concentrations of 0.5, 1.0, and 2.0 μmol/L were selected for subsequent experiments. (3) TUNEL fluorescence staining and flow cytometry showed that gambogic acid induced apoptosis of triple negative breast cancer stem cells in a dose-dependent manner (P < 0.05). qPCR and western blot assay confirmed that gambogic acid down-regulated mRNA and protein expression of protein C receptor, down-regulated Caspase-3, p-PI3K, and p-Akt protein expression, and up-regulated cleaved Caspase-3 protein expression (P < 0.05). siRNA-protein C receptor transfection experiments further confirmed that knockdown of protein C receptor expression in triple negative breast cancer stem cells increased cleaved Caspase-3 protein expression (P < 0.05), and down-regulated phosphorylation of PI3K/AKT signaling pathway (P < 0.05). Application of PI3K agonist 740 Y-P decreased cleaved Caspase-3 protein expression (P < 0.05), increased phosphorylation levels of p-PI3K and p-AKT (P < 0.05), and improved apoptosis to a certain extent. (4) The results show that gambogic acid may play a role in killing and inducing apoptosis of triple negative breast cancer stem cells by down-regulating protein C receptor, and the further molecular mechanism may be related to the inhibition of PI3K/AKT signaling pathway. Figures and Tables | References | Related Articles | Metrics

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Human leukocyte antigen matched sibling fresh cord blood transplantation for beta-thalassaemia major in children Wen Jianyun, Chen Libai, He Yuelin, Feng Xiaoqin, Liu Xuan, Xu Xiaoxiao, Li Xiu, Liu Qiujun, Wu Xuedong 2025, 29 (23):  4899-4906.  doi: 10.12307/2025.095 Abstract ( 97 )   PDF (925KB) ( 100 )   Save BACKGROUND: Allogeneic hematopoietic stem cell transplantation is currently the most effective method for the radical treatment of thalassemia major, but only half of patients can find compatible bone marrow or peripheral blood stem cells. Sib-derived umbilical cord blood stem cells have different characteristics from bone marrow and peripheral blood stem cells, and are a potential alternative source of hematopoietic stem cells for transplantation in patients with thalassemia major. OBJECTIVE: To investigate the therapeutic effect of human leukocyte antigen matched sibling fresh umbilical cord blood transplantation in the treatment of β-thalassemia major in children.  METHODS: Forty-eight children with β-thalassemia major, including 28 males and 20 females, with a median age of 4 years old, were selected from Nanfang Hospital of Southern Medical University from June 2010 to June 2020. All of them received fresh cord blood transplantation from human leukocyte antigen matched sibling. Transplantation conditioning adopted a myeloablative regiment without anti-thymocyte globulin. A combination of cyclosporine A and mycophenolate mofetil with or without short-range methotrexate was administered for graft-versus-host disease.  RESULTS AND CONCLUSION: (1) The median infused doses of total nucleated cells and CD34+ cells were 8.17×107/kg and 2.40×105/kg, respectively in 48 children. The median follow-up time after cord blood transplantation was 98 months, and 44 cases were successfully engrafted. The median time to neutrophil and platelet engraftment was 28 and 31 days, respectively. Among them, 37 cases were found to be donor-type complete chimerism detected as evidence of implantation after transplantation, 7 cases were found to be stable mixed chimerism. (2) Among the 44 children with successful implantation, four patients developed acute graft-versus-host disease, and were scored as grade I (n=2) and grade II (n=2). All the affected organs were skin, and no chronic graft-versus-host disease occurred. (3) After umbilical cord blood transplantation, cytomegalovirus infection and activation occurred in 5 of the 48 cases, sepsis in 12 cases, invasive fungal disease in 3 cases, stomatitis in 21 cases, hemorrhagic cystitis in 8 cases, and hepatic vein occlusion in 1 case. (4) Among 48 children, 47 patients survived; 1 died of severe pneumonia combined with acute heart failure 28 days after transplantation; 43 survived without disease; 3 had primary implantation failure, and 1 had pancytopenia after transplantation. The 5-year probabilities of overall survival and disease-free survival were 98% and 89%, respectively. The cumulative incidence of transplant-related deaths at 1 year was 2.1%. (5) The above results indicate that human leukocyte antigen matched sibling fresh umbilical cord blood transplantation is effective in the treatment of β-thalassemia major in children with a low incidence of graft-versus-host disease. Figures and Tables | References | Related Articles | Metrics

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Construction of tissue engineered urethra by combining acellular matrix with exosomes in small intestinal submucosa Wang Dan, Zhu Xiaojun, Li Zhicheng, Li Na 2025, 29 (23):  4907-4914.  doi: 10.12307/2025.086 Abstract ( 102 )   PDF (1391KB) ( 187 )   Save BACKGROUND: Small intestinal submucosal acellular matrix has been proven by clinical and basic studies to be useful for urethral repair and reconstruction. However, when applied alone, it has problems such as slow growth of host cells, difficulty in survival due to insufficient stent vascularization, and obstruction of reconstructed urethral stricture, and is only suitable for short urethral stricture. OBJECTIVE: To investigate the feasibility of constructing tissue engineered urethra with acellular matrix combined with exosomes in small intestinal submucosa. METHODS: Exosomes were isolated from rabbit bone marrow mesenchymal stem cells. The porcine small intestinal submucosal acellular matrix was prepared, and exosomes were loaded on the porcine small intestinal submucosal acellular matrix. The extracellular stroma-exosome (PKH26 dye labeled) complex of small intestinal submucosa was co-cultured with umbilical vein endothelial cells for 12 hours to observe the uptake of exosomes. The umbilical vein endothelial cells with good growth status were selected and cultured in three groups: the blank group was cultured routinely. The control group was added with small intestinal submucosal acellular matrix, and the experimental group was added with small intestinal submucosal acellular stromat-exosome complex. The angiogenesis was evaluated by scratch test, tube formation test, and angiogenic factor secretion test. Thirty New Zealand white rabbits were selected to establish a long (3 cm) urethral defect model, and the intervention was divided into three groups by random number table method (n=10). The single material group was implanted with small intestinal submucosal acellular matrix. The control group was implanted with small intestinal submucosal acellular matrix-bone marrow mesenchymal stem cell complex. The experimental group was implanted with small intestinal submucosal acellular matrix-exosome complex. Urethrography, urodynamic examination, and pathological observation of reconstructed urethral sections were performed 12 weeks after implantation. RESULTS AND CONCLUSION: (1) Exosomes in the acellular matrix of small intestinal submucosa could be taken up by umbilical vein endothelial cells under the fluorescence microscope. (2) Compared with the blank group and the control group, the experimental group could promote the migration of umbilical vein endothelial cells, angiogenesis ability, and the secretion of angiogenic factors vascular endothelial growth factor, hepatocyte growth factor, and interleukin 8 (P < 0.05). (3) Urethrography results showed that all 10 rabbits in the single material group had urethral stenosis; 2 out of 10 rabbits in the control group had urethral stenosis, and none of the 10 rabbits in the experimental group had urethral stenosis. The results of urodynamic examination showed that the maximum urethral pressure at 12 weeks after implantation was higher in the single material group than before surgery (P < 0.05), and the maximum urethral pressure at 12 weeks after implantation was lower in the control group and the experimental group than in the blank group (P < 0.05). Hematoxylin-eosin, Masson and immunohistochemical staining showed that in the single material group, there were obvious regenerated epidermis, a small amount of subcutaneous smooth muscle and blood vessels, mainly fibrous tissue hyperplasia, accompanied by obvious inflammatory cell infiltration. In the control group, there were more complete regenerated epithelium and a small amount of collagen, a large number of subcutaneous blood vessels and smooth muscle, accompanied by inflammatory cell infiltration. The experimental group showed complete regenerated epidermis, a large number of subcutaneous blood vessels and smooth muscle, and no obvious inflammatory cell infiltration. The positive expressions of AE1/AE3, alpha smooth muscle actin, and CD31 in the experimental group were higher than those in the single material group and the control group (P < 0.05). (4) The results show that the small intestinal submucosal acellular matrix-exosome tissue engineered urethra can repair the urethral defect by promoting angiogenesis. Figures and Tables | References | Related Articles | Metrics

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Effects of extracellular vesicles treated with Duhuo Jisheng Decoction on rheumatoid arthritis fibroblast-like synovial cells Yue Jinru, Zhang Yumin, Liu Jingshu, Bu Yanan, Wu Jingruo, Chen Jia, Wang Jianru 2025, 29 (23):  4915-4926.  doi: 10.12307/2025.081 Abstract ( 90 )   PDF (2251KB) ( 181 )   Save BACKGROUND: Duhuo Jisheng Decoction is a classic prescription for the treatment of rheumatoid arthritis, but its specific mechanism is not clear. Extracellular vesicles have the powerful function of inter-cell communication and signal transmission, and may be the signal carrier for the Decoction. OBJECTIVE: To explore the effects of serum extracellular vesicles treated with Duhuo Jisheng Decoction on the proliferation, migration, invasion, and apoptosis of rheumatoid arthritis fibroblast-like synovial cells. METHODS: The rheumatoid arthritis fibroblast-like synovial cell model was established by co-culturing with tumor necrosis factor-α in vitro. The experiment was divided into five groups: normal group, model group, serum treated with Duhuo Jisheng Decoction group, extracellular vesicles treated with Duhuo Jisheng Decoction group, and extracellular vesicles treated with normal saline group. The optimal concentration and time of drug-containing serum and extracellular vesicles were screened by CCK-8 assay. Expression of inflammatory cytokines in the supernatants of cells in each group was detected by ELISA. The migration ability of rheumatoid arthritis fibroblast-like synovial cells was detected by scratch assay. The invasive ability of cells was measured by Transwell Invasion assay. Hoechst staining was adoped to detect cell apoptosis. The expression levels of apoptosis-related genes and proteins were detected by qRT-PCR and western blot assay.  RESULTS AND CONCLUSION: (1) The optimal volume fraction of serum treated with Duhuo Jisheng Decoction was 10% and optimal mass concentration of extracellular vesicles treated with Duhuo Jisheng Decoction was 10 ng/mL; the optimal time for the interaction between the two was 24 hours. (2) Compared with the model group, serum treated with Duhuo Jisheng Decoction, extracellular vesicles treated with Duhuo Jisheng Decoction, and extracellular vesicles treated with normal saline could suppress the expression of inflammatory factors of rheumatoid arthritis fibroblast-like synovial cells (P < 0.05), scratch healing (P < 0.05), migration and invasion (P < 0.05). Moreover, the inhibition of extracellular vesicles treated with Duhuo Jisheng Decoction was more significant (P < 0.05). (3) Drug-containing serum and extracellular vesicles treated with Duhuo Jisheng Decoction promoted the apoptosis of rheumatoid arthritis fibroblast-like synovial cells. (4) Compared with the model group, serum treated with Duhuo Jisheng Decoction, extracellular vesicles treated with Duhuo Jisheng Decoction, and extracellular vesicles treated with normal saline could increase the expression of proapoptotic factors Caspase-3, Caspase-9, and Bax (P < 0.05) and decrease the expression of antiapoptotic factor Bcl-2 (P < 0.05). Moreover, extracellular vesicles treated with Duhuo Jisheng Decoction had a more significant regulatory effect on apoptosis-related factors. Above findings indicate that extracellular vesicles treated with Duhuo Jisheng Decoction can inhibit the excessive proliferation, migration, and invasion of rheumatoid arthritis fibroblast-like synovial cells and promote their apoptosis. Figures and Tables | References | Related Articles | Metrics

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Ectomesenchymal stem cells-derived extracellular vesicles promote neuronal axonal elongation Sun Haitao, Ren Chunpeng, Yang Yongtao, Huang Yonghui, Qin Rujie, Li Zhen 2025, 29 (23):  4924-4930.  doi: 10.12307/2025.100 Abstract ( 74 )   PDF (2077KB) ( 59 )   Save BACKGROUND: The occurrence of neuronal axonal injury can result in neurological dysfunction, and the facilitation of axonal elongation is anticipated to play a pivotal role in the treatment of diseases affecting the nervous system. OBJECTIVE: To investigate whether ectomesenchymal stem cells-derived extracellular vesicles can promote neuronal axonal elongation. METHODS: (1) Ectomesenchymal stem cells were obtained from nasal mucosa using the tissue adherence method, and the specific markers of were identified through immunofluorescence. Ectomesenchymal stem cells-derived extracellular vesicles were acquired via ultracentrifugation and identified. (2) Ectomesenchymal stem cells-derived extracellular vesicles (0, 0.5, 1.0, 1.5 mg/mL) were incubated with PC12 cells for 72 hours. The cytotoxicity and proliferation of ectomesenchymal stem cells-derived extracellular vesicles on PC12 cells were assessed using the CCK-8 assay. (3) Ectomesenchymal stem cells-derived extracellular vesicles (1.0 mg/mL) were incubated with PC12 cells or neurons for 72 hours. The changes in axon length were observed using microscopic analysis. The expression levels of axon-related markers β3-tubulin (early stage), growth associated protein 43 (middle stage), and neurofilament 200 (mature stage) were analyzed through real-time fluorescence quantitative PCR and Western blotting. These investigations aimed to explore the potential of ectomesenchymal stem cells-derived extracellular vesicles in promoting neurite elongation within PC12 cells or neurons.  RESULTS AND CONCLUSION: (1) The majority of the acquired ectomesenchymal stem cells exhibited a spindle-shaped morphology, while a minority displayed irregular shapes, and demonstrated high expression levels of mesenchymal stem cell-specific markers Nestin, CD44, and Vimentin. The obtained ectomesenchymal stem cells-derived extracellular vesicles fulfilled the biological criteria for extracellular vesicles. (2) Within the detected protein concentration range of 0.5 to 1.5 mg/mL, the proliferation of PC12 cells was promoted by ectomesenchymal stem cells-derived extracellular vesicles, and this effect was further enhanced with increasing concentrations. (3) Ectomesenchymal stem cells-derived extracellular vesicles increased the length of axons in PC12 cells and neurons and the expression of axon-related markers β3-tubulin, growth associated protein 43, and neurofilament 200. Above findings suggest that ectomesenchymal stem cells-derived extracellular vesicles have the potential to enhance neuronal axonal elongation.  Figures and Tables | References | Related Articles | Metrics

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Heme oxygenase 1 promotes differentiation of neural stem cells into neurons under oxidative stress condition Yu Qinghe, Cai Ziming, Tian He, Li Pian, Ruan Ye, Liang Jinzhu, Lin Shuhui, Lin Wenping 2025, 29 (23):  4931-4938.  doi: 10.12307/2025.513 Abstract ( 92 )   PDF (2723KB) ( 76 )   Save BACKGROUND: Studies have shown that upregulation of heme oxygenase-1 expression enhances cellular antioxidant and anti-apoptotic abilities. However, the effects of upregulating heme oxygenase-1 expression on the proliferation and differentiation of neural stem cells under oxidative stress conditions remain unclear.  OBJECTIVE: To investigate the influence of heme oxygenase-1 overexpression on the survival and differentiation capacity of neural stem cells under oxidative stress conditions.  METHODS: (1) Mouse primary neural stem cells were isolated and cultured from newborn Balb/c mice. Immunofluorescence was used to detect the neural stem cell marker Nestin. (2) Lentivirus was used to infect neural stem cells to induce heme oxygenase-1 overexpression. Flow cytometry was used to assess green fluorescent protein fluorescence. Western blot assay was performed to detect the expression levels of heme oxygenase-1. (3) H2O2 was added to the lentivirus-infected neural stem cell culture medium to simulate the oxidative stress microenvironment after spinal cord injury. Effects of heme oxygenase-1 overexpression on neural stem cell proliferation and apoptosis levels were analyzed using cell proliferation assay kits, cell apoptosis assay kits, and TUNEL staining kits. (4) The levels of lipid oxidation markers malondialdehyde, catalase, superoxide dismutase, and glutathione peroxidase were detected using assay kits. (5) Flow cytometry was used to measure intracellular reactive oxygen species levels, and neural stem cell differentiation into astrocytes and neurons. (6) The effect of heme oxygenase-1 overexpression on neuronal axon growth during neural stem cell differentiation was observed under optical and fluorescence microscopes.  RESULTS AND CONCLUSION: (1) Mouse neural stem cells exhibited stable morphology, good growth status, and high expression of Nestin as detected by immunofluorescence. (2) Western blot analysis showed that the overexpression of heme oxygenase-1 in the overexpression group was significantly higher than that in the empty carrier control group. Flow cytometry was used to detect the expression of green fluorescent protein in the neural stem cells of the heme oxygenase-1 overexpression group and empty vector control group. (3) Overexpression of heme oxygenase-1 maintained the proliferative activity of neural stem cells and significantly reduced the number of apoptotic cells under oxidative stress conditions. (4) Overexpression of heme oxygenase-1 inhibited lipid peroxidation of neural stem cells under oxidative stress microenvironment, enhanced the expression of enzymes related to maintaining the oxidative-reductive balance, and significantly reduced intracellular reactive oxygen species levels. (5) Overexpression of heme oxygenase-1 promoted the differentiation of neural stem cells into neurons and reduced differentiation into astrocytes. (6) The heme oxygenase-1 overexpression group exhibited longer axons, and more intercellular connections. The above results indicate that overexpression of heme oxygenase-1 can alleviate oxidative damage of H2O2-induced neural stem cells, reduce neural stem cell apoptosis, promote proliferation, and facilitate differentiation of neural stem cells into neurons. Figures and Tables | References | Related Articles | Metrics

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Fasudil alleviates beta-amyloid 1-42-induced apoptosis of SH-SY5Y cells Guo Minfang, Zhang Huiyu, Zhang Peijun, Su Qin, Jia Siwei, Yu Jiezhong 2025, 29 (23):  4939-4946.  doi: 10.12307/2025.090 Abstract ( 98 )   PDF (3746KB) ( 130 )   Save BACKGROUND: Fasudil has a regulatory effect on mitochondrial dynamics in the brain of Alzheimer’s disease mice and can inhibit neuroinflammation, but whether it can reduce the toxicity of β-amyloid protein by regulating mitophagy-NLRP3 inflammasome pathway remains unclear. OBJECTIVE: To investigate the regulatory effect of fasudil on β-amyloid 1-42-induced apoptosis and mitophagy and NLRP3 inflammasome in human derived neuroblastoma cell line SH-SY5Y cells. METHODS: SH-SY5Y cells were inoculated into the pore plate. After adhesion, cells were divided into three groups for intervention: No drug was added to the control group; 20 μmol/L β-amyloid 1-42 was added to the model group, and 20 μmol/L β-amyloid 1-42 and 15 mg/L fasudil were added to the fasudil group at the same time. After 24 hours of intervention, the cell activity was detected by MTT assay and apoptosis was detected by TUNEL staining. The expression of apoptosis-related proteins was detected by qRT-PCR and western blot assay. The expression of mitochondrial autophagy related proteins was detected by immunofluorescence staining and western blot assay. The expression of NLRP3 inflammasome related proteins was detected by immunofluorescence staining and western blot assay. RESULTS AND CONCLUSION: (1) Compared with control group, the cell activity of the model group was decreased and the apoptosis rate was increased (P < 0.05). Compared with model group, cell activity in the fasudil group was increased and apoptosis rate was decreased (P < 0.05). (2) The results of qRT-PCR and western blot assay showed that compared with the control group, the expression of Bax mRNA and protein was increased in the model group (P < 0.05), while the expression of Bcl-2 mRNA and protein was decreased (P < 0.05). Compared with the model group, the expression of Bax mRNA and protein was decreased (P < 0.05), and the expression of Bcl-2 mRNA and protein was increased (P < 0.05) in the fasudil group. (3) The results of immunofluorescence staining and western blot assay showed that compared with the control group, the expressions of PINK1, Parkinson’s disease protein and LC3 protein were decreased (P < 0.05), while the expression of p62 protein was increased (P < 0.05) in the model group. Compared with model group, the expression levels of PINK1, Parkinson’s disease protein, and LC3 protein were increased (P < 0.05), while the expression of p62 protein was decreased (P < 0.05) in the fasudil group. (4) The results of immunofluorescence staining and western blot assay showed that compared with the control group, the expression levels of NLRP3, ASC, Caspase-1, and interleukin1β protein were increased in the model group (P < 0.05). Compared with the model group, the expression levels of NLRP3, ASC, Caspase-1, and interleukin1β were decreased in the fasudil group (P < 0.05). (5) The results show that fasudil can reduce the apoptosis of SH-SY5Y cells induced by β-amyloid 1-42, and its mechanism may be related to the activation of mitophagy and the inhibition of NLRP3 inflammasome activation. Figures and Tables | References | Related Articles | Metrics

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Effect of aerobic exercise on mobilization and function of endothelial progenitor cells in patients with myocardial infarction Zhao Peng, Wang Congcong, Wang Chenyu 2025, 29 (23):  4947-4955.  doi: 10.12307/2025.096 Abstract ( 82 )   PDF (1469KB) ( 141 )   Save BACKGROUND: Exercise rehabilitation is an important means of non-drug treatment for patients with myocardial infarction. It can improve myocardial perfusion and cardiovascular function. The mechanism may be related to angiogenesis and repair mediated by vascular endothelial cells, while endothelial progenitor cells are the precursors of vascular endothelial cells. OBJECTIVE: To explore the impact of 12-week aerobic exercise on mobilization and function of endothelial progenitor cells in patients with myocardial infarction. METHODS: (1) A total of 66 patients with acute myocardial infarction who received percutaneous coronary intervention in First Affiliated Hospital of Zhengzhou University from January to October 2022 were selected and divided into exercise group (n=33) and control group (n=33) according to random number table method. Patients in the control group received conventional cardiac rehabilitation treatment for 12 weeks. Patients in the exercise group received conventional cardiac rehabilitation + 12 weeks of aerobic exercise intervention. Cardiopulmonary fitness, New York Heart Association classification, left ventricular ejection fraction, serum troponin I, brain natriuretic peptide levels, and peripheral blood endothelial progenitor cells were measured before and 72 hours after intervention. (2) Endothelial cells were isolated from peripheral blood of the two groups of patients before intervention and 72 hours after intervention, and the proliferation, adhesion, and migration ability of endothelial cells were detected.  RESULTS AND CONCLUSION: (1) At 72 hours after the intervention, New York Heart Association classification, serum troponin I and serum brain natriuretic peptide decreased (P < 0.05); peak oxygen uptake, maximum power, completion time of incremental load test, and left ventricular ejection fraction at peak exercise increased (P < 0.05); average heart rate and average subjective fatigue sensation score decreased (P < 0.05); peripheral blood endothelial cell count increased (P < 0.05) in the exercise group compared with those before intervention and the control group. (2) At 72 hours after intervention, the cell proliferation, adhesion, and migration ability of peripheral blood endothelial cells in the exercise group were higher than those before intervention and control group (P < 0.05). (3) Regular aerobic exercise can promote mobilization of endothelial progenitor cells and enhance ability of proliferation, adhesion, and migration, thereby improving clinical condition, cardiac function, and cardiopulmonary fitness of patients with myocardial infarction. Figures and Tables | References | Related Articles | Metrics

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Effects of sodium arsenite on lipid metabolism in human hepatocytes and regulatory factors Tian Zhenli, Zhang Xiaoxu, Fang Xingyan, Xie Tingting 2025, 29 (23):  4956-4964.  doi: 10.12307/2025.509 Abstract ( 108 )   PDF (3097KB) ( 228 )   Save BACKGROUND:  The liver, as the main target organ for arsenic toxicity, has become the focus of studies related to the mechanism of action of arsenic toxicity. OBJECTIVE: To investigate the effects of sodium arsenite (NaAsO2) on lipid metabolism, cell proliferation, apoptosis, and expression of related regulatory factors in human normal hepatocytes. METHODS: MIHA normal human hepatocyte cell lines were exposed to 0, 10, 20, and 30 µmol/L NaAsO2 for 48 hours. Cell morphology changes were observed by light microscopy. Cell viability was detected by CCK-8 assay. The cell serum total cholesterol, triacylglycerol, and total bile acids were detected by single-agent COD-PAP assay, single-agent GPO-PAP assay, and enzyme microplate assay. The intracellular lipid content was detected by oil red O staining. Cell proliferation was detected by Edu-488 infiltration. Cell cycle and apoptosis were detected by PI staining and Annexin V-FITC/PI dual-labeling combined with flow cytometry. The mRNA and protein expression levels of hepatocyte nuclear factor 4 alpha, cholesterol 7α-hydroxylase, and farnesoid X receptor were detected by real-time fluorescence quantitative PCR and western blot assay, respectively. RESULTS AND CONCLUSION: (1) Compared with the control group (0 µmol/L NaAsO2), with the increase of NaAsO2 concentration: MIHA cell viability decreased gradually. The content of total cholesterol and triacylglycerol in cell supernatant increased gradually, while the contents of total bile acids decreased gradually. The content of intracellular lipid increased gradually. The proportion of cells stagnating in S phase and G2/M phase gradually increased, and the apoptosis rate gradually increased. The expression level of hepatocyte nuclear factor 4 alpha mRNA did not show significant changes, while cholesterol 7α-hydroxylase and farnesoid X receptor mRNA expression levels decreased. The protein expression levels of hepatocyte nuclear factor 4 alpha, cholesterol 7α-hydroxylase, and farnesoid X receptor decreased gradually. (2) NaAsO2 has cytotoxicity, significantly reduces MIHA cell viability, induces cell steatosis, inhibits cell proliferation, and induces cell apoptosis. NaAsO2 down-regulates hepatocyte nuclear factor 4 alpha protein expression and the transcription and expression of cholesterol 7α-hydroxylase and farnesoid X receptor, which further induces lipid metabolism disorders in hepatocytes. Figures and Tables | References | Related Articles | Metrics

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Effects of cannabidiol on hepatic stellate cell activation and hepatic fibrosis induced by transforming growth factor beta1 Wang Lian, Xie Na, Zhao Peiling, Chen Hao, Li Duyou, Wang Yuping 2025, 29 (23):  4965-4974.  doi: 10.12307/2025.097 Abstract ( 70 )   PDF (2329KB) ( 98 )   Save BACKGROUND: Cannabidiol has anti-inflammatory, antioxidant, and other pharmacological effects, and has no mental activity, so the research in liver disease is increasing day by day, but its effect on transforming growth factor-β1/Smad signal transduction pathway in hepatic stellate cells is not clear. OBJECTIVE: To investigate the effect of cannabidiol on transforming growth factor-β1/Smad signal transduction pathway in hepatic stellate cells and its possible mechanism of anti-hepatic fibrosis. METHODS: (1) In vitro experiment: Rat hepatic stellate cell line (HSC-T6) was selected and cultured in six groups. The control group was routinely cultured for 24 hours. The simple drug group was cultured with cannabidiol for 24 hours. The modeling group was cultured with transforming growth factor β1 for 24 hours. The modeling + low-dose drug group, the modeling + high-dose drug group, and the modeling + positive control group were cultured with transforming growth factor β1 for 24 hours, 1, 5 μmol/L cannabidiol and silymarin were cultured for 24 hours. After culture, the mRNA expression of α-smooth muscle actin and type I collagen, the levels of interleukin 1β and tumor necrosis factor α, and the protein expression of type I collagen and transforming growth factor β1/Smad signal transduction pathway were detected in each group. (2) In vivo experiments: C57BL/6J mice were randomly divided into five groups with eight mice in each group. Models were not established in the sham operation group. The liver fibrosis models were established by biliary ligation in the modeling group, the modeling+low-dose drug group, the modeling+high-dose drug group, and the modeling+positive control group. At 3 weeks after the modeling, 4, 8 mg/kg cannabidiol or silymarin were injected intraperitoneally, once a day, for 7 consecutive days. After administration, the liver function, liver pathological morphology, expression levels of α-smooth muscle actin, type I collagen, and transforming growth factor β1/Smad signal transduction pathway related protein were detected in each group.  RESULTS AND CONCLUSION: (1) In vitro experiment: Compared with the control group, mRNA expression of α-smooth muscle actin and type I collagen, interleukin 1β and tumor necrosis factor α, and protein expression of type I collagen, transforming growth factor β1 and p-Smad2/3 in HSC-T6 cells were increased (P < 0.05), while Smad7 protein expression was decreased (P < 0.05) in the modeling group. Two doses of cannabidiol could improve the above changes in HSC-T6 cells induced by transforming growth factor β1, and the improvement was more obvious in the modeling+high-dose drug group. (2) In vivo experiment: Compared with sham operation group, the activities of serum alanine aminotransferase and aspartate aminotransferase were increased (P < 0.05), inflammatory cell infiltration and collagen content in liver tissue were increased (P < 0.05), and the transforming growth factor β1/Smad signal transduction pathway was activated; α-smooth muscle actin and type I collagen expression levels were increased (P < 0.05) in the modeling group. Two doses of cannabidiol could reduce the changes of the above indexes in the modeling mice, and the effect was more obvious in the modeling+high-dose drug group. (3) It is indicated that cannabidiol inhibits hepatic fibrosis by suppressing the activation of transforming growth factor-β1/Smad signal transduction pathway in hepatic stellate cells. Figures and Tables | References | Related Articles | Metrics

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Application and problems in targeted delivery of antitumor drugs by exosomes derived from engineered mesenchymal stem cells Wang Shuangmin, Wang Xianyao, He Zhixu 2025, 29 (23):  4975-4983.  doi: 10.12307/2025.092 Abstract ( 210 )   PDF (1311KB) ( 296 )   Save BACKGROUND: Mesenchymal stem cell-derived exosomes inherit the advantages of low immunogenicity and strong tumor homing ability, garnering significant attention in targeted drug delivery. However, exosomes are prone to rapid clearance from the circulation before reaching target cells. Additionally, due to the complex surface properties and uptake mechanisms of exosomes, their targeting specificity is not distinctly apparent, necessitating engineered strategies to enhance delivery efficiency.  OBJECTIVE: To elucidate mechanisms for enhancing the delivery efficiency of exosomes, preclinical applications, and challenges encountered by reviewing various approaches to engineering modifications of exosomes derived from mesenchymal stem cells so as to provide a theoretical basis for further clinical applications.  METHODS: Relevant literature from the establishment of databases to 2024 was retrieved from databases including CNKI, VIP, WanFang, and PubMed. The search terms used were “mesenchymal stem cells, exosomes, engineered exosomes, targeted delivery, antineoplastic agents” in both English and Chinese. Literature focusing on engineered mesenchymal stem cell-derived exosomes for targeted delivery of antitumor drugs was screened, resulting in the inclusion of 85 articles for review and analysis. RESULTS AND CONCLUSION: (1) The engineering modification of mesenchymal stem cell-derived exosomes is complex and diverse. The delivery efficiency of exosomes can be improved by significantly enhancing their targeting ability to organs or tissues, increasing their residence time in the blood circulation, and reducing the expression of tumor-promoting molecules in exosomes. (2) Current examples of mesenchymal stem cell-derived exosome delivery of traditional and novel drugs demonstrate their tremendous potential. (3) There are still some safety issues that preclude their clinical translation. Future research will further improve and delve into the delivery mechanisms, with the hope of developing more efficient and safe therapeutic strategies. Figures and Tables | References | Related Articles | Metrics

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Electrotactic migration and mechanisms of stem cells Han Fang, Shu Qing, Jia Shaohui, Tian Jun 2025, 29 (23):  4984-4992.  doi: 10.12307/2025.082 Abstract ( 139 )   PDF (1053KB) ( 137 )   Save BACKGROUND: With the deepening of research on stem cell technology, how to make its accurate homing has become a major problem in clinical application. In addition to the induction of drugs and chemokines, electric fields are also widely used to guide the directional migration of stem cells. They can enhance their migration speed and orientation.  OBJECTIVE: To summarize the effect of an electric field on the characteristics of stem cell migration and analyze the possible mechanism of action.  METHODS: PubMed and CNKI databases were searched to collect relevant literature up to March 2024, with Chinese and English search terms “stem cells, direct current electric field, pulsed electric field, migration, electric field device, mechanism.” Literature that was not available in full text and unrelated to the topic was excluded.   RESULTS AND CONCLUSION: A total of 58 articles were included according to the screening requirements, including 15 Chinese articles and 43 English articles. In the literature, the effects of different parameters of the electric field on the migration of adipose-derived mesenchymal stem cells, bone marrow mesenchymal stem cells, neural stem cells, epidermal stem cells, human embryonic stem cells, and human induced pluripotent stem cells and its mechanism were studied in a migration device. (1) As a simple, non-invasive, and stable intervention method, the electric field plays an active role in guiding the directional migration of stem cells. (2) Different types of stem cells had different directions of electrotaxis migration, and the migration speed and directionality of most stem cells increased with the increase of electric field intensity. (3) Different electric field devices have different focuses in observing stem cell migration, and the relevant devices can be selected according to the purpose of the experiment. (4) The mechanism of electrotaxis migration of different stem cells is not completely the same. MAPK pathway, ROCK activation, and PI3K function are involved in the migration process of most stem cells, and other protein complexes and signaling pathways are involved in the regulation of this process. (5) In addition to different electric field parameters, cell senescence and culture environment also affect the results of electrotaxis migration. In summary, as an important signal that affects the migration characteristics of stem cells, the application of electric field combined with other emerging materials has shown certain potential in tissue engineering. It is expected to play a more important role in guiding stem cells to home, promoting bone tissue regeneration and repair, and making greater breakthroughs in the research of the nervous system, autoimmune system, tumors, and other diseases. Figures and Tables | References | Related Articles | Metrics

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Role and influence of compressive stress on cells in vitro Yan Pengan, Cai Yifan, Yan Zhenxing, Wei Yuqiao, Geng Bin, Xia Yayi 2025, 29 (23):  4993-5001.  doi: 10.12307/2025.093 Abstract ( 100 )   PDF (945KB) ( 182 )   Save BACKGROUND: Wolff’s law points out that the lack of mechanical stress in the body will lead to the degradation of the microstructure of bone tissue, mass loss, and metabolic disorders, and eventually lead to osteoporosis, which suggests that mechanical stress plays an important role in the growth, reconstruction, and formation of bone tissue. At present, the relevant studies concerning mechanical stress on osteoblasts mainly focus on fluid shear force, but it is difficult to intervene in vivo. Meanwhile, some studies have found that compressive stress can also play a similar role in fluid shear force to a certain extent. Exploring the mode of action and influence of compressive stress on cells in vitro experiments can enrich the interaction relationship between mechanical stress and cells. It helps provide a theoretical basis for studies of metabolic bone diseases, including osteoporosis, and other diseases. OBJECTIVE: To review in vitro experiments, the application of compressive stress to cells, different biological behaviors caused by cells, the possible signaling pathways, and possible future applications. METHODS: We searched PubMed, Web of Science, CNKI, and WanFang databases from January 2000 to March 2024 to include all articles related to compressive stress on cells, including basic research and microscopic mechanism studies, using search terms “compressive stress, mechanical stress, hydrostatic pressure, cell” in Chinese and English. Finally, the 63 included articles were reviewed.  RESULTS AND CONCLUSION: (1) There are various ways to apply compressive stress, and different experimental equipment has different ways of pressurizing cells, so it is necessary to further standardize the experimental equipment, standardize the pressurization unit, reduce the confounding factors, and make the reference and comparability between different experimental groups. (2) Compressive stress can cause changes in cell proliferation, differentiation, autophagy, apoptosis, migration, etc., and the effect of compressive stress is time- or dose-dependent in most cases. (3) At present, most in vitro experimental studies have shown that compressive stress may mainly act on osteoblasts through MAPK signaling pathway and Wnt/β-catenin signaling pathway, causing osteoblasts to produce different responses. (4) The effect of compressive stress on different cells is not the same, and its possible biological effects need to be studied. (5) Further research on compressive stress is helpful to provide a theoretical basis for treatment in orthopedics, stomatology, tumors and other fields, and gentle disinfection using hydrostatic pressure is a promising disinfection method. Figures and Tables | References | Related Articles | Metrics

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Different strategies to enhance mesenchymal stem cells in treatment of liver fibrosis: analysis of efficacy and potential risks Xu Yan, Wang Xuesong, Zhou Lin, Zhou Xiaolei, Jin Yu, Ye Junsong 2025, 29 (23):  5002-5012.  doi: 10.12307/2025.085 Abstract ( 125 )   PDF (1516KB) ( 121 )   Save BACKGROUND: At present, a large number of studies have shown that mesenchymal stem cells can be combined with different strategies to more effectively improve liver fibrosis and inhibit its progression to end-stage liver disease.  OBJECTIVE: To explore the mechanism of mesenchymal stem cells combined with different strategies to improve liver fibrosis compared with mesenchymal stem cells alone.  METHODS: The first author used computers to search CNKI, WanFang, VIP, PubMed, Web of Science, and Nature databases involving mesenchymal stem cells combined with different strategies to improve liver fibrosis. The search terms were “mesenchymal stem cells, liver fibrosis, combination therapy, liver stellate cells” in Chinese, and “mesenchymal stem/stromal cells, liver/hepatic fibrosis/cirrhosis, combination therapy, hepatic stellate cells/HSCs” in English. By quickly browsing the title and abstract of the article, excluding the articles that are not closely related to the topic, 104 articles were finally selected for review analysis. RESULTS AND CONCLUSION: Mesenchymal stem cells improve liver fibrosis by differentiating into hepato-like cells, inhibiting hepatic stellate cell activation, immune regulation, and other mechanisms. However, the low rate of liver colonization, low survival rate, and short action time of mesenchymal stem cells after transplantation limit their clinical application. Mesenchymal stem cells can improve liver fibrosis through a combination of drugs, gene modification, cytokines and other strategies, and the efficacy is better than that of mesenchymal stem cells alone. Moreover, the combination of mesenchymal stem cells and different strategies can effectively improve liver fibrosis by promoting mesenchymal stem cell homing, inhibiting hepatic stellate cell activation, regulating the microenvironment, and regulating signaling pathways. Mesenchymal stem cells can also show better liver-derived differentiation, homing and survival functions in reducing liver fibrosis through pretreatment, miRNA regulation and combination with other cells. The combination of mesenchymal stem cells and different strategies cannot avoid the potential risks of mesenchymal stem cells alone in the treatment of liver fibrosis, and the safety of these strategies (drugs, gene modifications, cytokines, etc.) is also worth considering. In addition, the number and route of mesenchymal stem cell transplantation need to be further studied.  Figures and Tables | References | Related Articles | Metrics

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Hot topics on exosomes as drug delivery system in central nervous system diseases Lin Huijie, Huang Yun, Huang Zhihua, Jiang Lixia 2025, 29 (23):  5013-5021.  doi: 10.12307/2025.084 Abstract ( 122 )   PDF (1232KB) ( 198 )   Save BACKGROUND: The use of exosomes as drug carriers can not only precisely target the therapeutic site, but also increase the local concentration, opening up a new way for drugs to enter the central nervous system. OBJECTIVE: To explore the biogenesis and biological functions of exosomes and summarize the current state-of-the-art regarding extracellular vesicles as drug carriers in the treatment of central nervous system diseases. METHODS: The first author searched Web of Science, PubMed, and CNKI for relevant literature from January 1976 to January 2024. The English search terms were “exosomes, extracellular vesicles, central nervous system, drug delivery, ischemic stroke, Alzheimer’s disease, Parkinson’s disease, spinal cord injury, brain tumor.” The Chinese search terms were “exosomes, extracellular vesicles, central nervous system diseases, drug delivery, stroke, Alzheimer’s disease, Parkinson’s disease, spinal cord injury, brain tumor.” Finally, 94 articles were included for analysis.  RESULTS AND CONCLUSION: (1) Exosomes can easily cross the blood-brain barrier and deliver proteins, metabolites, and nucleic acids to recipient cells to regulate cellular metabolism. Since exosomes are small vesicles secreted by cells, they have a much lower circulating immunogenicity and can be less likely to be recognized and cleared by macrophages in the internal circulation. (2) Exosomes can be engineered to deliver different therapeutically ingredients, including RNA, proteins, chemotherapeutic drugs, and immunomodulators, and are capable of delivering them to the desired target areas. Engineered modified exosomes have better targeting properties. Furthermore, this exosome-mediated delivery is extremely low in immunogenicity and is expected to provide a safer and more effective method for precision therapy of central nervous system diseases in the future. Figures and Tables | References | Related Articles | Metrics

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Crossroads of colorectal cancer progression and suppression: efficacy and challenges of mesenchymal stem cell therapy interventions Guo Zhao, Zhuang Haoyan, Shi Xuewen 2025, 29 (23):  5022-5030.  doi: 10.12307/2025.078 Abstract ( 147 )   PDF (1033KB) ( 271 )   Save BACKGROUND: Early treatment methods for colorectal cancer include endoscopy and surgical resection, but there are many postoperative complications. Chemotherapy is the most common treatment for late-stage colorectal cancer, but chemotherapy can cause gastrointestinal dysfunction, bone marrow suppression, liver and kidney function damage, and other adverse reactions. As a result, most patients are not proactive and do not cooperate with treatment.  OBJECTIVE: To review the mechanism of action, latest treatment progress, and current problems of mesenchymal stem cells in the treatment of colorectal cancer, and provide a basis for future clinical application.   METHODS: PubMed, CNKI, and WanFang databases were searched for relevant literature using the keywords of “mesenchymal stem cells, colorectal cancer, cancer stem cell, tumor microenvironment” in Chinese and English, respectively. Finally, 119 articles were included for analysis.   RESULTS AND CONCLUSION: (1) Mesenchymal stem cells have both promoting and inhibiting effects on colorectal cancer. (2) The tumor homing characteristics of mesenchymal stem cells enable them to migrate accurately to the tumor site and release drugs, which increases the safety and effectiveness of the treatment of colorectal cancer. (3) Exosomes derived from mesenchymal stem cells can serve as good carriers and shows a good application prospect in the targeted therapy of colorectal cancer. (4) Using viral vectors, non-viral vectors, or other transfection tools, drugs with mature anti-tumor effects can be loaded into mesenchymal stem cells for the treatment of colorectal cancer. (5) The combined use of mesenchymal stem cells and chemotherapy drugs can improve the efficacy of chemotherapy drugs and reduce the adverse reactions of chemotherapy drugs. (6) The mechanism by which mesenchymal stem cells promote the development of colorectal cancer is mainly related to the expression status of signal transduction and chemotactic factors in colorectal cancer cells and the transformation of mesenchymal stem cells into cancer-related fibroblasts. (7) Mesenchymal stem cells may have the characteristics of driving cancer stem cells, promoting tumor initiation and increasing tumor invasion. (8) There are still some unavoidable problems in the treatment of colorectal cancer with mesenchymal stem cells: lack of standardized treatment plans and efficacy evaluation, high treatment costs, preservation and transportation of mesenchymal stem cells, and the proportion of combined use of mesenchymal stem cells and chemotherapy drugs. Figures and Tables | References | Related Articles | Metrics

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Immunomodulatory effect of umbilical cord mesenchymal stem cells on type 2 diabetes mellitus Chen Chunlan, Ye Meiyi, Pan Yuwei, Yuan Jia, Zhou Pengjun 2025, 29 (23):  5031-5040.  doi: 10.12307/2025.507 Abstract ( 152 )   PDF (2091KB) ( 128 )   Save BACKGROUND: Umbilical cord mesenchymal stem cells present immunomodulatory function and multidirectional differentiation potential. Umbilical cord mesenchymal stem cells can actively improve the chronic low-grade inflammation state in type 2 diabetes mellitus and which is important for preventing the development of type 2 diabetes mellitus progression.  OBJECTIVE: To review the research progress of umbilical cord mesenchymal stem cells in the treatment of type 2 diabetes mellitus through immunomodulatory effect.  METHODS: Using “umbilical cord mesenchymal stem cells, UC-MSCs, mesenchymal stem cells, MSCs, type 2 diabetes mellitus, T2DM, immunity, insulin resistance, inflammation” as Chinese and English search terms, articles were searched on CNKI, Web of Science and PubMed databases. Relevant reviews, research papers and theses were screened and 88 papers were collected for summarization based on the inclusion and exclusion criteria.  RESULTS AND CONCLUSION: Umbilical cord mesenchymal stem cells can effectively delay the occurrence and development of type 2 diabetes mellitus by reducing inflammatory response, inducing macrophages to M2 polarization, increasing the sensitivity of target organs to insulin, improving insulin resistance, and alleviating the dysfunction of islet beta cells through immune regulation. However, before umbilical cord mesenchymal stem cell transplantation can become a routine treatment, large-scale basic and applied basic research is needed to determine the optimal treatment regimen and efficacy. Figures and Tables | References | Related Articles | Metrics

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Molecular mechanism of adipose tissue-derived mesenchymal stem cells in treatment of acute liver injury Yang Na, Liu Yang, Hao Huiqin 2025, 29 (23):  5041-5050.  doi: 10.12307/2025.065 Abstract ( 88 )   PDF (1094KB) ( 189 )   Save BACKGROUND: Acute liver injury can result from a variety of causes, and if not treated in time, it will develop into acute liver failure and seriously affect the life safety of patients. As the liver is the largest immune organ and metabolic organ, there is no optimal treatment for acute liver injury. The adipose tissue-derived mesenchymal stem cell has multi-differentiation potential and immunomodulatory activity, so it has been gradually becoming an effective tool for the treatment of acute liver injury. OBJECTIVE: To review the progress and molecular mechanism of adipose tissue-derived mesenchymal stem cell and its modification in different ways in the treatment of acute liver injury. METHODS: Relevant articles published from 2000 to 2023 were retrieved from PubMed, Web of Science, and CNKI databases. English search terms were “acute liver injury, liver injury, adipose tissue-derived mesenchymal stem cell, liver injury repair, stem cell transplantation, stem cell repair, cell surface engineering, stem cell modification.” Chinese search terms were “acute liver injury, liver injury, adipose tissue-derived mesenchymal stem cell, liver injury repair, stem cell transplantation, stem cell repair, stem cell modification.” Totally 62 articles of the latest research progress in this field were summarized and analyzed. RESULTS AND CONCLUSION: (1) Adipose tissue-derived mesenchymal stem cell as a potential stem cell with multi-directional differentiation has biological advantages in the treatment of acute liver injury. Compared with the other two major types of mesenchymal stem cell that is bone marrow mesenchymal stem cell and umbilical cord mesenchymal stem cell, they are more widely sourced, easily accessible and have fewer ethical issues, and more self-renewal than bone marrow mesenchymal stem cell. (2) Adipose tissue-derived mesenchymal stem cell may play a therapeutic role in acute liver injury by regulating immune responses, differentiating into hepatocytes, and secreting growth factors and exosomes. It can reduce the expression of inflammatory factors in serum and the infiltration of inflammatory cells in liver tissue, also can inhibit the pyroptosis and autophagy levels to promote regeneration of sinusoidal endothelial cells and hepatocyte, and ultimately improve liver damage. At present, no studies have shown which mechanism is the best mechanism for adipose tissue-derived mesenchymal stem cells to treat acute liver injury, and most opinions believe that these molecular mechanisms interact with each other to play a synergistic role in treatment. (3) Biomaterials modification and drug pretreatment can improve the efficacy of adipose tissue-derived mesenchymal stem cell in the treatment of acute liver injury. On the one hand, biomaterials and drug modifications can enhance the functions of adipose tissue-derived mesenchymal stem cell, such as enhancing the ability of proliferation and migration, increasing the level of growth factors secreted, and enhancing the anti-inflammatory ability and promoting the survival of adipose mesenchymal stem cells at the injury site. On the other hand, biomaterials and drug modifications can inhibit the activation of inflammatory cells at the injured site and promote the growth of blood to improve the success rate of transplantation. (4) In summary, adipose tissue-derived mesenchymal stem cell plays an important role in the treatment of acute liver injury by secreting growth factors and exosomes, regulating the immune response, and promoting liver regeneration. With the development of science and technology, biomaterials and drug modification can enhance the self-renewal ability of adipose tissue-derived mesenchymal stem cell and improve the local microenvironment of acute liver injury. It provides a new way to promote the clinical application of adipose tissue-derived mesenchymal stem cell in the treatment of acute liver injury. Figures and Tables | References | Related Articles | Metrics

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Visualization analysis of knowledge map and trends in glymphatic system research Ma Xingyi, Li Huijing, Li Juan, Zhong Dongling, Zhang Yuan, Tang Hong, Li Yuxi, Jin Rongjiang 2025, 29 (23):  5051-5060.  doi: 10.12307/2025.094 Abstract ( 92 )   PDF (3469KB) ( 410 )   Save BACKGROUND: The clearance pathway of metabolic waste in the brain is crucial for maintaining neural homeostasis. The accumulation of metabolic waste disrupts this equilibrium, representing a common pathological feature of many central nervous system diseases. In recent years, research focusing on the glymphatic system has emerged as a hotspot in the nervous system field.   OBJECTIVE: To construct a knowledge map of glymphatic system research, visually analyze the current state of research, main hotspots, and future development trends within this area. METHODS: Utilizing CiteSpace, VOSviewer, and the Bibliometrix package in the R language environment, this study conducted an in-depth visual analysis of glymphatic system-related literature from the Web of Science Core Collection database, spanning from January 2012 to March 2024. This analysis included authors, institutions, countries, journals, keywords, and co-citation frequencies.  RESULTS AND CONCLUSION: A total of 687 related articles were included in this study. The number of publications in this field increased year by year, showing an explosive growth trend in the past three years. The countries, institutions, and authors with the largest number of publications in this research field were the United States, University of Rochester, and Professor Maiken Nedergaard. The journal with the highest number of publications was JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM. The high-frequent and high-central keywords mainly focused on the mechanism such as cerebrospinal fluid hydrodynamics, neurological diseases such as Alzheimer’s disease, and imaging techniques such as diffusion tensor imaging. The literature with the highest co-citation frequency was a classic review of the glymphatic system. The above results show that the research of glymphatic system is an emerging and active field, which has attracted wide attention at home and abroad and gradually expand from theoretical research to clinical practice. Figures and Tables | References | Related Articles | Metrics