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28 November 2019, Volume 23 Issue 33 Previous Issue    Next Issue

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Potential mechanisms of bone marrow stem cells in the treatment of ischemic stroke based on bioinformatics An Taijian, Zhang Wei, Yang Hong, Wang Qingfeng 2019, 23 (33):  5249-5255.  doi: 10.3969/j.issn.2095-4344.1843 Abstract ( 501 )   PDF (1122KB) ( 462 )   Save BACKGROUND: Stem cell therapy has received sustained attention in the treatment of prognosis of ischemic stroke. However, little research has been done on its complex regulatory mechanism. OBJECTIVE: To study the molecular regulatory network of stem cell therapy for ischemic stroke by bioinformatics. METHODS: DisGeNET database was used to collect the background network of ischemic stroke, and then GEO online database was used to obtain differentially expressed genes before and after treatment with bone marrow stem cells. Gene targeting was performed in the above genes to obtain stroke-related targets. DAVID and STING databases were used to analyze the relationship between these target genes. RESULTS AND CONCLUSION: In the DisGeNET database, there were 393 molecular targets for ischemic cerebrovascular accident regulation. Thirty-nine molecular targets were confirmed to be related to ischemic cerebrovascular accident in the data set of stem cell therapy in the GEO database. Among them, 30 were down-regulated, including FBN1, NPY, MMP10, ITGB3, and GLA; and 9 were up-regulated, including EZH2, ESR1, IL16, and LGALS2. (2) Based on the corresponding interaction relation described in String database, the above 39 targets could be obtained. There were 10 nodes with a greater node degree, namely TP53, SPP1, VCAM1, PTGS2, ESR1, F3, TIMP2, CD40, EZH2, and ITGB3. Except for up-regulated genes, ESR1 and EZH2, the others were down-regulated genes. (3) The main regulatory pathways involved in this process included: vascular shear stress regulation and relaxin signaling pathways directly acting on blood vessels; inflammatory-related signaling pathways such as IL-7, NFKB; neuroactive ligand-receptor, allograft rejection and other signaling pathways. Figures and Tables | References | Related Articles | Metrics

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Effects of insulin-like growth factor-binding protein 5 on osteogenic differentiation of periodontal ligament stem cells stimulated by inflammatory cytokines Liu Dayong, Wang Yingchengyao, Sun Ruixin, Liu Fan, Jia Zhi 2019, 23 (33):  5256-5262.  doi: 10.3969/j.issn.2095-4344.1823 Abstract ( 469 )   PDF (872KB) ( 341 )   Save BACKGROUND: Previous studies have confirmed that insulin-like growth factor-binding protein 5 (IGFBP5) is highly expressed in dental stem cells and exerts roles by activating multiple signaling pathways. However, it is unclear whether IGFPB5 is involved in the regulation of mesenchymal stem cell osteogenic differentiation in inflammatory microenvironment. OBJECTIVE: To study the influence and molecular mechanism of IGFBP5 on osteogenic differentiation of periodontal ligament stem cells under inflammatory microenvironment, and to provide a new therapeutic target for periodontal tissue regeneration in inflammatory microenvironment. METHODS: After periodontal ligament stem cells were isolated and collected, their surface antigen markers were detected by flow cytometry. The stable IGFBP5 knock-down cell lines were established, and were cultured in osteogenic differentiation medium containing tumor necrosis factor α and interleukin 17. We then detected alkaline phosphatase activities and mRNA expression of marker genes relating to osteogenic differentiation and histone methyltransferase. The study protocol was implemented in line with the ethic requirements of Tianjin Medical University Hospital of Stomatology. RESULTS AND CONCLUSION: (1) The osteogenic capacity of periodontal ligament stem cells decreased under stimulation of tumor necrosis factor α and interleukin 17. Compared with the blank control group, the activity of alkaline phosphatase and the expressions of osteogenic differentiation related genes OCN and BSP were significantly reduced after osteoblastic induction. (2) Gene silencing of IGFBP5 allowed tumor necrosis factor α and interleukin 17 to further inhibit the osteogenesis of periodontal ligament stem cells, characterized by decreased alkaline phosphatase activity and further decreased expression of osteoblastic differentiation related genes OCN and BSP. (3) Inflammatory factor stimulation and gene silencing of IGFBP5 also affected the mRNA expression of histone demethylases KDM2A, KDM3B, KDM5B and JMJD6. To conclude, IGFBP5 may play a positive role in the osteogenic differentiation of periodontal ligament stem cells. Figures and Tables | References | Related Articles | Metrics

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Allogeneic chimeric antigen receptor T-cell therapy for recurrent chronic myeloid leukemia in lymphoid blast crisis after allogeneic hematopoietic stem cell transplantation: a two-case report and literature review Wang Zhen, Zhang Xuejun, Chen Yuqing, Zhang Lei, Zhu Zunmin, Li Yulong, Huang Zhoufeng, Lian Cheng, Shi Mingyue, Zhang Hongsheng, Wang Fuxu, Wen Shupeng, Yang Jing, Zheng Meiqiong, Sun Kai 2019, 23 (33):  5263-5268.  doi: 10.3969/j.issn.2095-4344.1827 Abstract ( 589 )   PDF (635KB) ( 426 )   Save BACKGROUND: In recent years, tumor immunotherapy has developed rapidly. Most scholars have focused on the single antibody treatment with autologous chimeric antigen receptor T-cell (CAR-T), but poor quality and small number of cultured cells are encountered. Therefore, allogeneic CAR-T cells have a better developmental potential. OBJECTIVE: To investigate the efficacy and safety of allogeneic CAR-T cells in the treatment of recurrent leukemia after allogeneic hematopoietic stem cell transplantation. METHODS: Two patients with relapsed refractory chronic myeloid leukemia in lymphoid blast crisis after allogeneic hematopoietic stem cell transplantation were treated with allogeneic CAR-T cells. Their clinical data were analyzed and relevant literature was reviewed. RESULTS AND CONCLUSION: Case 1 was hospitalized because of fever and fatigue for 5 days, and was diagnosed as chronic myeloid leukemia in lymphoid blast crisis by bone marrow cell morphology, flow cytometry, chromosome analysis, fusion gene and other related examinations. After oral imatinib combined with low dose chemotherapy, HLA10/10 matched haploid transplantation from daughter to mother proceeded smoothly. Three months after transplantation, BCR-ABL (p210) was positive, and chimera: donor cells accounted for 67.4%. After treatment with fludarabine+cyclophosphamide regimen, anti-CD19 CAR-T cells were infused at a dose of 5 ×106 cells/kg. Two weeks later, BCR-ABL (p210) turned negative and chimera: donor cells accounted for 99.62%. During the period, cytokine release syndrome level 1 appeared and symptomatic treatment was performed. The follow-up lasted for 6 months. Case 2 was treated in the local hospital in April 2011 because of left upper abdomen fullness for 1 year and night sweat for 15 days. One year later, it progressed to chronic myeloid leukemia in lymphoid blast crisis with T315I mutation. HLA 7/10 matched haploid stem cell transplantation from little brother to brother was performed after remission by chemotherapy. Anti-CD19 CAR-T cells were transfused at 2×105/kg in the second relapse in 2018. During this period, cytokine release syndrome level 4 appeared. Chronic myeloid leukemia continued to alleviate for over 2 months and then relapsed resulting in death. Thus, the donor-derived CAR-T cells can be considered for the treatment of recurrent chronic myeloid leukemia in lymphoid blast crisis after allogeneic hematopoietic stem cell transplantation. It can be transfused repeatedly. It is safe and effective, and the incidence of Graft-versus-host disease is low. Sequential treatment with anti-CD22 CAR-T cells is safe and effective. References | Related Articles | Metrics

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Thrombopoietin improves platelet recovery after allogeneic hematopoietic stem cell transplantation for severe aplastic anemia: an assessment of safety and efficacy  Guo Zhi, Ren Hua, Ji Yong, Chen Liping, Chen Lina, Liu Xuanyong, Zheng Shanshan, Liu Xiaodong, Chen Huiren 2019, 23 (33):  5269-5274.  doi: 10.3969/j.issn.2095-4344.1835 Abstract ( 481 )   PDF (716KB) ( 335 )   Save BACKGROUND: Studies have shown that the use of thrombopoietin after allogeneic hematopoietic stem cell transplantation has a certain role in hematopoietic regulation and hematopoietic reconstitution, providing a theoretical basis for clinical application. OBJECTIVE: To analyze the clinical efficacy and safety of thrombopietin in the treatment of severe aplastic anemia after hematopoietic stem cell transplantation. METHODS: Fifty patients receiving allogeneic hematopoietic stem cell transplantation from January 2012 to January 2017 including 28 males and 22 females with the mean age of 27.8 (16-48) years were enrolled. Patients received 300 U/kg thrombopietin (treatment group, n=25) subcutaneously, which began at 7 days after transplantation, or were only treated with symptomatic treatment (control group, n=25). Time node of platelet implantation in two groups of patients ≥ 20×109/L, 50×109/L, and 100×109/L and median Infusion times of platelet were compared between two groups. The study protocol was approved by the Ethics Committee of Army General Hospital, and enrolled patients signed informed consent prior to the inception of the trial. RESULTS AND CONCLUSION: The median time of platelet implantation ≥ 20×109/L, 50×109/L, and 100×109/L was 16.2, 19.3, and 30.2 days in the treatment group and 18.8, 25.8, and 38.5 days in the control group, respectively. The time of platelet implantation time in the treatment group was 2.6, 6.5, and 8.3 days earlier than that in the control group. The median number of irradiated platelet implantation was 6.8 times in the treatment group and 9.5 times in the control group. There was a significant difference between the two groups (P < 0.05). All the patients were followed up to July 2017, and the disease-free survival rates were 80% in the treatment group and 72% in the control group. These findings indicate that thrombopietin can promote platelet implantation and recovery after allogeneic hematopoietic stem cell transplantation, and is well tolerated, which is worthy of further clinical application. Figures and Tables | References | Related Articles | Metrics

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Bone marrow mesenchymal stem cells co-transfected by lentivirus-mediated bone morphogenetic protein 2 and vascular endothelial growth factor 165 in combination with demineralized bone matrix for treating rabbit femoral head necrosis Ma Yuegang, Li Qiang, Tao Xuan, Zhou Zhenjie, Zhu Lunjing, Duan Jiangtao 2019, 23 (33):  5275-5280.  doi: 10.3969/j.issn.2095-4344.1828 Abstract ( 524 )   PDF (811KB) ( 141 )   Save BACKGROUND: Bone morphogenetic protein 2 (BMP-2) and vascular endothelial growth factor 165 (VEGF-165) play important roles in bone repair. It is of great significance to treat bone injury by lentivirus-transfected bone marrow mesenchymal stem cells combined with demineralized bone matrix. OBJECTIVE: To observe the therapeutic effects of bone marrow mesenchymal stem cells with lentivirus-mediated BMP-2 and VEGF-165 co-transfection and demineralized bone matrix in a rabbit model of osteonecrosis of the femoral head, so as to explore the feasibility of dual genes in the bone repair. METHODS: Femoral head necrosis model was prepared by liquid nitrogen freezing combined with core decompression. Rabbit models successfully prepared were divided into three groups (n=12/group): non-transfection group, treated with bone marrow mesenchymal stem cells combined with demineralized bone matrix; single gene transfection group, treated with BMP-2-transfected bone marrow mesenchymal stem cells combined with demineralized bone matrix; dual-gene transfection group, treated with BMP-2 and VEGF-165 co-transfected bone marrow mesenchymal stem cells combined with demineralized bone matrix. Four rabbits from each group were sacrificed at 3, 6, and 9 weeks postoperatively. Western blot was used to detect the expression of BMP-2 protein in the femoral head of each group. Hematoxylin-eosin staining was used to observe the repair of femoral head necrosis in each group. The study protocol was approved by the Animal Ethics Committee of Guilin Medical University. RESULTS AND CONCLUSION: BMP-2 positively expressed in all groups at 3, 6, and 9 weeks postoperatively, and the positive expression of target protein was significantly higher in the two transfection groups than the non-transfection group (P < 0.05). The positive expression of BMP-2 in the two transfection groups showed an increasing trend at three time periods. At 3 weeks postoperatively, there was no difference in the BMP-2 expression between the two transfection groups, while the BMP-2 expression was significantly increased in the dual-gene transfection group compared with the single gene transfection group at 6 and 9 weeks postoperatively (P > 0.05). In the dual gene transfection group, new osteophytes could fill in the defect of the femoral head at 9 weeks postoperatively, while in the other two groups, new osteophytes formed were not enough to fill in the defect. Hematoxylin-eosin staining indicated that primary trabeculae were formed in the non-transfection group, but there were more necrotic cells and less bone trabeculae. In the single gene transfection group, a large amount of trabeculae formed with good shape, some of which however were inferior to normal bone tissues because of fractures. In the dual gene transfection group, a mass of mature and dense trabeculae were formed and had normal shape. To conclude, lentivirus-mediated BMP-2 and VEGF-165 co-transfection is superior to single BMP-2 transfection in the combination of bone marrow mesenchymal stem cells and demineralized bone matrix for treating femoral head necrosis. Moreover, in vivo expression of target protein persists for a long time. Figures and Tables | References | Related Articles | Metrics

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Co-culture of bone marrow mesenchymal stem cells and islet cells influences islet function Yang Huiming, Yu Xing, Fang Yuhui 2019, 23 (33):  5281-5285.  doi: 10.3969/j.issn.2095-4344.1837 Abstract ( 489 )   PDF (604KB) ( 148 )   Save BACKGROUND: Bone marrow mesenchymal stem cells can secrete various growth factors and support hematopoiesis, but whether they can protect and repair the function of islet cells remains unclear. OBJECTIVE: To investigate the effect of rat bone marrow mesenchymal stem cells co-cultured with islet cells on rat islet function. METHODS: Bone marrow was extracted from male Sprague-Dawley rats aged 8-9 weeks. Bone marrow mesenchymal stem cells were isolated from bone marrow using density gradient centrifugation combined with adherent culture. Collagenase P (1 g/L, 10 mL) was injected into the common bile duct of another male Sprague-Dawley rats aged 8-9 weeks, and the pancreas was cut off to isolate and purify islet cells using Histopaque discontinuous density gradient. Islet cells with intact cell membrane were selected by hand using 1-mL pipet pipette under microscope, and co-cultured with third-generation bone marrow mesenchymal stem cells. The experiment was divided into control group (single islet cell culture), direct co-culture group (islet cells co-cultured with bone marrow mesenchymal stem cells in culture plates), indirect culture group 1 (indirect co-culture with Transwell dish), and indirect culture group 2 (islet cell culture with bone marrow mesenchymal stem cell medium). The morphology and growth of islets were observed during culture. Insulin secretion was measured by ELISA on the 3rd, 7th, and 14th days after culture. The study protocol was approved by the Ethics Committee of Yanbian University Affiliated Hospital. RESULTS AND CONCLUSION: The results of variance analysis showed that insulin secretion was significantly increased when islet cells were co-cultured with bone marrow mesenchymal stem cells, and reached a peak on the 7th day of co-culture. Insulin secretion was significantly higher in the indirect co-culture group 1 than the direct co-culture group (P < 0.05). To conclude, the indirect co-culture method of Transwell dish can significantly improve insulin secretion, and the rational co-culture time is 7 days. Figures and Tables | References | Related Articles | Metrics

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Induced pluripotent stem cell transplantation for systemic lupus erythematosus in a mouse model Ma Linjie, Xue Wentao, Tan Jupeng 2019, 23 (33):  5286-5292.  doi: 10.3969/j.issn.2095-4344.1826 Abstract ( 526 )   PDF (992KB) ( 300 )   Save BACKGROUND: The biological characteristics of autologous mesenchymal stem cells for transplantation of systemic lupus erythematosus (SLE) are susceptible to the disease. Cell therapy with low immunogenic stem cells that are not affected by the disease has become a research hotspot. To date, treatment of systemic lupus erythematosus with autologous induced pluripotent stem cell transplantation has not been reported. OBJECTIVE: To evaluate the therapeutic effect of transplantation of induced pluripotent stem cells derived from autologous fibroblasts in mice with systemic lupus erythematosus. METHODS: Fifty-four 8-week-old MRL/lpr mice were randomly divided into three groups. Model control group was not treated, reagent control group was injected with PBS solution through tail vein, and stem cell treatment group was injected with autologous induced pluripotent stem cells through tail vein. Serum creatinine, urea nitrogen, anti-double-stranded DNA antibodies and anti-nuclear antibodies were detected by ELISA at 4 weeks of cell treatment. Kidney tissue morphology was observed by hematoxylin-eosin staining on paraffin sections. Urinary protein concentrations were detected by Coomassie brilliant blue method. Flow cytometry was used to detect the percentage of regulatory T cells in peripheral blood, percentage of splenic dendritic cells, and ratio of splenic helper T1 cells to helper T2 cells. RESULTS AND CONCLUSION: The levels of serum creatinine, urea nitrogen, anti-double-stranded DNA antibody and anti-nuclear antibody in the stem cell treatment group were lower than those in the model control and reagent control groups, while decreased urine protein concentration, increased percentages of regulatory T cells in peripheral blood, increased percentage of splenic dendritic cells, and increased splenic Th1/Th2 ratio were detected in the stem cell treatment group as compared with the other two groups. Compared with the model control and reagent control groups, there was decreased glomerular volume, reduced number of mesangial cells, degeneration of renal tubular epithelial cells and decreased tubular type in the stem cell treatment group. In summary, induced pluripotent stem cell transplantation from autologous skin fibroblasts for treat systemic lupus erythematosus can alleviate renal tissue damage, improve renal function and play an immunoregulatory role in mice. Figures and Tables | References | Related Articles | Metrics

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Amplification and identification of human placental mesenchymal stem cells Ma Chen, Li Xiaoguo, Xu Mingjun, Ma Xiaona, Ma Xiaowei 2019, 23 (33):  5293-5299.  doi: 10.3969/j.issn.2095-4344.1830 Abstract ( 412 )   PDF (1102KB) ( 315 )   Save BACKGROUND: As a seed cell for tissue engineering, placental mesenchymal stem cells are widely used in the treatment of clinical diseases and clinical research due to their multi-directional differentiation, low immunogenicity, and immunomodulation. OBJECTIVE: To identify human placental mesenchymal stem cells from the Stem Cell Research Institute of Ningxia Medical University General Hospital according to the definition of mesenchymal stem cells, and to provide reliable protection for subsequent experiments. METHODS: The human placental mesenchymal stem cells were obtained from the Stem Cell Research Institute of Ningxia Medical University General Hospital. Cells attached to plastic culture dishes or culture flasks were detected, and cell morphology was observed intermittently. The cultured third-generation human placental mesenchymal stem cells were tested for cell surface specific antigen by flow cytometry, and were cultured in adipogenic, osteogenic and chondrogenic induction media, respectively. After 21 days of induction, Oil red O, alizarin red and toluidine blue were used for cell staining to observe the differentiation ability of human placental mesenchymal stem cells into fat, bone and chondrocytes. The study protocol was approved by the Ethics Committee of Ningxia Medical University General Hospital (approval No. 2018-047). RESULTS AND CONCLUSION: The third-generation human placental mesenchymal stem cells cultured in vitro showed a vortex-like adherent growth. The single cell was fusiform with fibroblast-like appearance. Human placental mesenchymal stem cells had a special cellular immunological phenotype: CD105, CD90, and CD73 were positively expressed, and CD34, CD45, CD14 and HLA-DR were negatively expressed. The human placental mesenchymal stem cells were induced to differentiate in vitro after 21 days, and were positive for alizarin red, oil red O, and toluidine blue staining. As per the definition of mesenchymal stem cells, human placental mesenchymal stem cells from the Stem Cell Research Institute of Ningxia Medical University General Hospital meet the characteristics of mesenchymal stem cells, providing good guarantee for further experiments. Figures and Tables | References | Related Articles | Metrics

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Ginsenoside-induced bone marrow mesenchymal stem cell intervention can affect healing and Wnt/beta-catenin signaling in rats with diabetic skin ulcer Ma Hongwei, Liu Panyun, Zhang Yaqiong 2019, 23 (33):  5300-5306.  doi: 10.3969/j.issn.2095-4344.1838 Abstract ( 498 )   PDF (885KB) ( 255 )   Save BACKGROUND: Previous studies have shown that bone marrow mesenchymal stem cells can certainly promote wound healing, and considerably accelerate the recovery of wound skin. However, relevant research on gene and drug regulation has yet to make breakthrough progress. OBJECTIVE: To analyze the effects of ginsenoside-induced bone marrow mesenchymal stem cells on skin healing of rats with diabetic skin ulcer and their effects on Wnt/β-catenin signaling. METHODS: Sixty-one SPF-level Wistar male rats were selected, one of them was used for the culture of bone marrow mesenchymal stem cells, and the other 60 were randomized into four groups: blank control group, model group (treated with 1 mL of culture medium via tail vein), single cell treatment group (treated with 1 mL of bone marrow mesenchymal stem cell suspension via tail vein, 2.0×109/L) and ginsenoside-induced cell treatment group (treated with 1 mL of ginsenoside-induced bone marrow mesenchymal stem cell suspension via tail vein, 2.0×109/L). Animal models of diabetic skin ulcer were made in all groups except the blank control group. Treatments in each group were performed at 6 hours after modeling. The study protocol was approved by the Animal Ethics Committee of the 251st Hospital of PLA with approval No. 20161211 in December 2016. RESULTS AND CONCLUSION: Compared with the blank control group, the serum levels of interleukin-1, high-sensitivity C-reactive protein and tumor necrosis factor-α increased and the serum levels of platelet-derived growth factor, vascular endothelial growth factor and basic fibroblast factor decreased in the model group. Compared with the model group, the serum levels of interleukin-1, high-sensitivity C-reactive protein and tumor necrosis factor-α decreased significantly and the serum levels of platelet-derived growth factor, vascular endothelial growth factor and basic fibroblast factor increased significantly in the single cell treatment and ginsenoside-induced cell treatment groups. Compared with the single cell treatment group, the serum levels of interleukin-1, high-sensitivity C-reactive protein and tumor necrosis factor-α decreased significantly and the serum levels of platelet-derived growth factor, vascular endothelial growth factor and basic fibroblast factor increased significantly in the ginsenoside-induced cell treatment group. Compared with the blank control group, the number of fibroblasts and density of newly born capillaries decreased in the model group. Compared with the model group, the number of fibroblasts and density of newly born capillaries increased in the two cell treatment groups. Compared with the single cell treatment group, the number of fibroblasts and density of newly born capillaries increased in the ginsenoside-induced cell treatment group. Compared with the blank control group, the expression of Wnt4 and β-catenin mRNA increased in the model group. Compared with the model group, the expression of Wnt4 and β-catenin mRNA decreased in the two cell treatment groups. Compared with the single cell treatment group, the expression of Wnt4 and β-catenin mRNA decreased in the ginsenoside-induced cell treatment group. These findings therefore indicate that ginsenoside-induced bone marrow mesenchymal stem cells considerably reduce the levels of serum inflammatory cytokines, increase the level of growth factors, and downregulate the expression of related proteins in the Wnt/β-catenin signaling pathway to accelerate wound healing. Figures and Tables | References | Related Articles | Metrics

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Treatment of steroid-induced femoral head necrosis by hypoxia-induced bone marrow stromal stem cell transplantation Dong Wentao, Zhou Yongfang, Zhang Jian, Zhang Fei, Wu Jianhua, Wang Qiang, Xu Fengyang, Peng Wuxun 2019, 23 (33):  5307-5311.  doi: 10.3969/j.issn.2095-4344.1821 Abstract ( 292 )   PDF (726KB) ( 246 )   Save BACKGROUND: Bone marrow stromal stem cell transplantation has been explored for the treatment of femoral head necrosis at present, but there are some problems to be solved such as unsatisfactory therapeutic effect. OBJECTIVE: To observe the effect of hypoxic preconditioning of bone marrow stromal stem cells on steroid-induced femoral head necrosis in rabbits. METHODS: Rabbit bone marrow stromal cells were isolated, purified and cultured. They were cultured in a hypoxic incubator (2% O2) for 48 hours. Cell counting kit-8, flow cytometry, and ELISA assay were used to detect cell viability, apoptosis and secretion of cytokines, respectively. Forty New Zealand rabbits were randomly divided into control group, model group, stem cell group and hypoxia-treated stem cell group, 10 in each group. Steroid-induced femoral head necrosis model was established in the latter three groups. Bone marrow stromal stem cells that were normally cultured or induced by hypoxia were transplanted in the latter two groups. After 6 weeks of transplantation, femoral head tissue from each rabbit was taken out for general observation and hematoxylin-eosin staining. RESULTS AND CONCLUSION: (1) After hypoxic preconditioning, the viability of bone marrow stromal stem cells increased significantly, while the cell apoptosis decreased considerably. The levels of cytokines such vascular endothelial growth factor, growth factor and insulin-like growth factor 1 released into the supernatant increased markedly. (2) The surface of the femoral head of the model group was damaged and collapsed. The surface of the femoral head of the model group was dark in color and congested, and the bone became brittle. The surface of the femoral head of the stem cell group was light-colored, and the congestion alleviated. The surface of the femoral head of the hypoxia-treated stem cell group was smooth, flat and light-colored, with no obvious congestion. In this group, the femoral head was close to the normal bone of the control group. (3) In the control group, the trabecular structure was intact and osteoclasts were evenly dispersed. In the model group, the trabeculae disappeared obviously, and empty bone lacunae appeared. A large number of osteoclasts were observed. In the stem cell group, the trabeculae were blurred and the osteoclasts were still densely arranged. In the hypoxia-treated stem cell group, the trabecular structure remained intact and the accumulation of osteoclasts decreased. These results suggest that the transplantation of bone marrow stromal stem cells after hypoxic preconditioning has a better effect on the treatment of steroid-induced avascular necrosis of the femoral head. Figures and Tables | References | Related Articles | Metrics

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Antagonistic effect of methylene blue on aniline-induced DNA damage of mouse bone marrow cells Jiang Chao, Hu Yulong 2019, 23 (33):  5312-5316.  doi: 10.3969/j.issn.2095-4344.1836 Abstract ( 469 )   PDF (617KB) ( 230 )   Save BACKGROUND: With the continuous application of single cell gel electrophoresis technology in DNA damage and repair, we explore target organs of aniline genotoxicity and kinetic effects of methylene blue, providing a new strategy for the treatment of aniline poisoning symptoms. OBJECTIVE: To investigate the antagonistic effect of methylene blue on aniline-induced DNA damage of bone marrow cells in mice. METHODS: Kunming mice were intragastrically administered with aniline at 5, 50, 100, and 200 mg/kg (aniline-administered groups). Corresponding methylene blue treatment groups, negative control group, and blank control group were set. Ten mice in each group were exposed to poison for 6 days. The mouse bone marrow cells were taken for single cell gel electrophoresis to observe the DNA damage and repair of bone marrow cells. RESULTS AND CONCLUSION: (1) Compared with the negative control group and the blank control group, the DNA tail length and tail moment of the bone marrow cells in 100 and 200 mg/kg aniline-administered groups increased significantly (P < 0.01). The tail length and tail moment of the 5 and 50 mg/kg methylene blue treatment groups were slightly lower than those of the corresponding aniline-administered groups (P > 0.05), while the tail length and tail moment of the 100 and 200 mg/kg aniline-administered group showed a significant increase as compared with the corresponding methylene blue treatment groups (P < 0.01). Overall findings indicate that DNA damage in mouse bone marrow cells gradually aggravates with the increase of aniline concentration, and methylene blue has a certain repair effect on aniline-induced DNA damage in mouse bone marrow cells. Figures and Tables | References | Related Articles | Metrics

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Effects of total saponins of Achyranthes bidentata on cytokine profiles of synovial fluid in experimental rabbits with knee osteoarthritis Gao Kun, Zhang Yong, Chen Dayu, Yu Weiji, Sun Shufen, Wu Yihong, Lin Zhanpeng, Cao Yafei 2019, 23 (33):  5317-5321.  doi: 10.3969/j.issn.2095-4344.1842 Abstract ( 459 )   PDF (562KB) ( 212 )   Save BACKGROUND: Previous studies have shown that synovial fluid cytokines are important factors responsible for knee pain. Achyranthes bidentata can promote the repair of knee chondrocytes, relieve inflammation of the knee joint, and ease knee pain. Whether Achyranthes bidentata can regulate the level of cytokines in the synovial fluid of knee osteoarthritis is still unclear. OBJECTIVE: To investigate the effect of total saponins of Achyranthes bidentata on cytokine profiles of synovial fluid in experimental rabbits with knee osteoarthritis. METHODS: Eight New Zealand rabbits were randomized into experimental and control groups (n=4/group). A rabbit model of knee osteoarthritis was established. At 2 days after modeling, the total saponins of Achyranthes bidentata and distilled water were administered in the experimental and control group, respectively. Range of motion of the knee joint was measured after 2 weeks of administration. The synovial fluid of the knee joint was extracted from each rabbit. The levels of inflammatory cytokines and chemokines were measured by Luminex. The levels of matrix metalloproteinases 1, 2, 3 mRNA were measured by ELISA. The study protocol was approved by the Animal Ethics Committee of Guangzhou University of Chinese Medicine (approval No. 2018-31). RESULTS AND CONCLUSION: The range of motion of the knee joint in the experimental group was significantly higher than that in the control group (P < 0.05). Compared with the control group, the expression levels of inflammatory factors interleukin 1α, interleukin 1β, interleukin 10, tumor necrosis factor α, chemokines CCL3, CXCL8, CXCL9, matrix metalloproteinases 1, 2, 3 decreased significantly after treatment (P < 0.05). These findings indicate that Achyranthes bidentata total saponins can alleviate knee dysfunction in knee osteoarthritis rabbits, and reduce the level of cytokines in the synovial fluid of the knee joint, thus reducing inflammation and protecting the cartilage. Figures and Tables | References | Related Articles | Metrics

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Human induced pluripotent stem cell transplantation for hypoxic-ischemic encephalopathy in neonatal mice Gong Jiao, Liu Ming 2019, 23 (33):  5322-5327.  doi: 10.3969/j.issn.2095-4344.1825 Abstract ( 505 )   PDF (761KB) ( 224 )   Save BACKGROUND: Stem cell transplantation for the treatment of hypoxic-ischemic encephalopathy in neonatal mice mainly concerns mesenchymal stem cells and neural stem cells, but not enough emphasis has been placed on lateral ventricular human induced pluripotent stem cells transplantation. OBJECTIVE: To observe the effects of transplantation of human induced pluripotent stem cells on neuronal apoptosis and cognitive function in neonatal mice with hypoxic-ischemic encephalopathy. METHODS: Sixty 7-day-old C57BL/6j mice were randomly divided into five groups, 12 in each group. Normal control group was not treated, sham operation group was not subjected to ligation of the right common carotid artery, and model group was subjected to ligation of the right common carotid artery and hypoxic intervention. Phosphate buffer solution was injected into the right ventricle after model establishment in placebo treatment group, and human induced pluripotent stem cells were injected into the right ventricle after model establishment in stem cell treatment group. After 14 days of treatment, immunohistochemical fluorescence staining was used to observe the distribution of human induced pluripotent stem cells in brain tissues, TTC staining was used to detect the damage area and calculate the volume of brain tissues, and TUNEL staining was used to detect the apoptotic rate of neurons in brain tissues. After 28 days of treatment, cylindrical test was used to detect the frequency of limb uses in each group, and water maze method was used to detect escape latency in mice. RESULTS AND CONCLUSION: (1) After 14 days of treatment, human induced pluripotent stem cells were evenly distributed in the affected side and contralateral brain tissues of mice. (2) After 14 days of treatment, the infarct volume of brain tissue in the stem cell treatment group was smaller than that in the model group and placebo treatment group (P < 0.01). (3) After 14 days of treatment, the apoptotic rate of neurons in the brain tissue in the stem cell group was lower than that of the model group and placebo treatment group (P < 0.01). (4) After 28 days of treatment, the frequency of ischemic limb use in the stem cell treatment group was higher than that in the model group and the placebo treatment group, and shorter escape latency was detected in the stem cell treatment group than in the model group and the placebo treatment group (P < 0.01). These findings indicate that the transplantation of induced pluripotent stem cells into the lateral ventricle could migrate into the mouse brain tissue, reduce the apoptosis of neurons and the volume of cerebral infarction, and improve neurological dysfunction in the model mice. Figures and Tables | References | Related Articles | Metrics

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Differentiation of bone marrow mesenchymal stem cells into hepatocytes under induction by interleukin-1 beta combined with hepatocyte growth factor in vitro Pan Lijuan, Wang Rongli 2019, 23 (33):  5328-5333.  doi: 10.3969/j.issn.2095-4344.1831 Abstract ( 302 )   PDF (794KB) ( 179 )   Save BACKGROUND: Bone marrow mesenchymal stem cells have multi-lineage differentiation potential and can differentiate into a variety of cell lineages. It is currently considered that bone marrow mesenchymal stem cells are the most promising seed cells for the treatment of various end-stage liver diseases including liver failure. How to induce cell differentiation is the focus of research. OBJECTIVE: To explore the ability of hepatocyte growth factor combined with interleukin-1β to induce bone marrow mesenchymal stem cells to differentiate into hepatocytes, and to find a suitable induction method. METHODS: Passage 3 bone marrow mesenchymal stem cells were divided into control group, hepatocyte growth factor group, and low-, middle- and high-dose combined induction group (20 μg/L hepatocyte growth factor+5, 10, 20 μg/L interleukin-1β respectively). Morphological changes of the cells in each group were observed under inverted microscope. Immunohistochemical methods were used to detect expression of cytokeratin 18 and albumin at 7, 14, and 21 days of induction. RESULTS AND CONCLUSION: There was no morphological change in the control group, whereas in the other four groups, the cells gradually developed from fusiform and prismatic to polygonal and round, similar to the morphology of hepatocytes. No cytokeratin 18 and albumin expression was observed in the control group, while cytokeratin 18 and albumin positively expressed in the other four groups, and the expression levels were gradually increased with the extension of induction time (P < 0.05). At each time point, the expression of albumin and CK18 upregulated with the increase of interleukin-1β concentration (P < 0.05). Therefore, combined use of hepatocyte growth factor and interleukin-1β has better induction effect than hepatocyte growth factor used alone. Moreover, the induction ability of the combined use is strengthened with the increase of interleukin 1β concentration between 0-20 μg/L. Figures and Tables | References | Related Articles | Metrics

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Comparing biological characteristics of five kinds of mesenchymal stem cells Liu Chao, Zhang Lijun, Tao Hao, Du Xinjie, Wang Rui, Li Wenjing, Ding Shumei, Wang Yi, Jiang Lei, Huang Yuxiang 2019, 23 (33):  5334-5340.  doi: 10.3969/j.issn.2095-4344.1834 Abstract ( 825 )   PDF (847KB) ( 152 )   Save BACKGROUND: Various methods have been introduced to isolate mesenchymal stem cells of different origins. A full understanding of similarities and differences among mesenchymal stem cells of different origins will contribute to the rational and standardized application of mesenchymal stem cells in clinical practice. OBJECTIVE: To compare the biological characteristics of mesenchymal stem cells of different origins. METHODS: We collected umbilical cord, placenta and part of adipose tissues that were shed from parturients after cesarean delivery, and decidua basalis-derived mesenchymal stem cells, chorionic villi-derived mesenchymal stem cells, adipose-derived mesenchymal stem cells, mesenchymal stem cells at the junction between umbilical cord and placenta, and umbilical cord mesenchymal stem cells were cultured by trypsinization or tissue explant method. There were three kinds of stem cell culture media, including stem cell culture medium containing fetal bovine serum, stem cell culture medium containing cord blood lysate, and serum-free stem cell culture medium. Cell diameter, surface markers and multi-directional differentiation ability under different culture conditions were examined. Gene expression of different mesenchymal stem cells was analyzed by retrieval of the GEO database. RESULT AND CONCLUSION: Under different culture conditions, there were no differences in cell size and cell cycle. The diameter of mesenchymal stem cells cultured in serum-free culture system was decreased, while the diameter of placenta-derived mesenchymal stem cells cultured in the stem cell culture medium containing cord blood lysate increased. Mesenchymal stem cells of five origins had similar surface markers, osteogenic, chondrogenic and adipogenic abilities, in which adipose-derived mesenchymal stem cells have stronger adipogenic ability. Moreover, adipose-derived mesenchymal stem cells are different from other kinds of stem cells in term of gene expression, and have complex extracellular matrix. Figures and Tables | References | Related Articles | Metrics

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Regulation of miRNA206/histone deacetylase 4 by electroacupuncture promotes myogenic differentiation during multifidus muscle repair  Liu Tong, Yu Jiani, Zou Dehui, Kuang Weichuan, Wang Xiaoyin, Wen Xi, Jiang Ye, Qiu Xiaojia, Zeng Yao, Liu Yue 2019, 23 (33):  5341-5346.  doi: 10.3969/j.issn.2095-4344.1816 Abstract ( 592 )   PDF (845KB) ( 247 )   Save BACKGROUND: Our preliminary studies on animal and cell experiments have shown that electroacupuncture can improve the expression of Pax7 and myogenic differentiation antigen in injured multifidus muscle and facilitate the repair of multifidus muscle injury. Studies have also shown that miRNA206 promotes myogenic differentiation mainly through inhibition of histone deacetylase 4. OBJECTIVE: To explore the effect of electroacupuncture on miRNA206/histone deacetylase 4 during muscle regeneration after bupivacaine-induced multifidus muscle injury in rats. METHODS: The study protocol was approved by the Animal Ethics Committee of Guangdong Second Hospital of Traditional Chinese Medicine with the approval No. 048604. Thirty male Sprague Dawley rats were randomly divided into control group, model group and electroacupuncture group (n=10/group). Rat models of multifidus muscle injury were established by injecting 0.5% bupivacaine hydrochloride in model and electroacupuncture groups, while normal saline injection was only given in control group. No acupuncture intervention was given in the control and model groups. Electroacupuncture at bilateral Shenshu (BL23) and Weizhong (BL40) acupoints was given in the electroacupuncture group. Needles were then stimulated electrically using a Han’s Acupoint Nerve Stimulator for 20 minutes daily for 7 continuous days, with a density wave, frequency of 2 Hz/10 Hz and continuous current of 1 mA. At 7 days of intervention, morphological changes of the multifidus muscle was observed using hematoxylin-eosin staining, and qRT-PCR was used to detect miRNA206 expression, and western blot was used to observe the expression of myogenic differentiation antigen, Myogenin and histone deacetylase 4 in the multifidus muscle. RESULTS AND CONCLUSION: (1) Hematoxylin-eosin staining indicated that, most of the skeletal muscle fibers in the control group were neatly arranged at 7 days of treatment, with no obvious damage and macrophage infiltration. The muscle fibers in the model group were largely damaged, but partially repaired and there were still a lot of macrophages. More newborn muscle fibers and fewer macrophages could be seen in the electroacupuncture group compared to the model group. (2) Western blot results indicated that the expression of myogenic differentiation antigen, Myogenin and histone deacetylase 4 proteins was significantly increased in the model group relative to the control group after 7 days of treatment (P < 0.05 or P < 0.01). Compared with the model group, the expression of myogenic differentiation antigen and Myogenin increased significantly in the electroaupuncture group (P < 0.01), but the expression of histone deacetylase 4 decreased significantly (P < 0.01). (3) qRT-PCR results indicated that the expression of miRNA206 in the model group was significantly higher than that in the control group (P < 0.01) and lower than that in the electroacupucture group after 7 days of treatment (P < 0.05). Therefore, electroacupuncture could accelerate myogenic differentiation after multifidus muscle injury, which may be achieved by improving the expression of miRNA206 to inhibit activity of histone deacetylase 4. Figures and Tables | References | Related Articles | Metrics

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Comparison of different non-contact ultrasound methods for obtaining adipose-derived stromal vascular fraction cells Wei Jiatian, Lu Peiling, Huang Jing, Liu Xue, Cai Haiming, Wu Guohui, Zhang Linghua, Nie Yunfei 2019, 23 (33):  5347-5352.  doi: 10.3969/j.issn.2095-4344.1824 Abstract ( 565 )   PDF (719KB) ( 281 )   Save BACKGROUND: It is of great clinical significance to explore methods for efficient and stable access to stromal vascular component cells. Current methods for separating stromal vascular components mainly include enzymatic hydrolysis, bolus injection method, and contact ultrasonic pulverization method. For contact ultrasonic pulverization, there are many problems to be solved, such as low safety, low cell survival rate, and material contamination. Therefore, non-contact ultrasonic pulverization can solve these problems well. OBJECTIVE: To find an optimal method for harvesting adipose-derived stromal vascular fraction cells by non-contact ultrasound approach. METHODS: The human body fat tissue (subcutaneous fat) used was provided by the Plastic Surgery Hospital of Chinese Family Physician. Patients were eligible if they had no other basic diseases in the physical examination. All the patients were informed of study protocol and signed informed consent before sampling. The fat tissues were treated with three different ultrasonic instruments (approximately 800 W for ultrasonic cleaner, 1 000 W for ultrasonic cell crusher, and 1 200 W for non-contact ultrasonic cell crusher) for 15, 20, and 25 minutes. Contact ultrasonic crushing method (100 W, 16 seconds) was used as control. Stromal vascular fraction cell size, number of survived cells, cell viability, cell fragmentation rate and microbial infection were measured. The study was implemented in accordance with the relevant ethical requirements of Plastic Surgery Hospital of Chinese Family Physician. RESULTS AND CONCLUSION: The viability of stromal vascular fraction cells obtained by the three methods was significantly higher than that by the contact ultrasonic crushing method (P < 0.05). The contamination degree of stromal vascular fraction cells obtained by the three methods was significantly lower than that obtained by the contact ultrasonic crushing method (P < 0.05). There was no significant difference in the size of stromal vascular fraction cells obtained by the three methods (P > 0.05). The cell fragments of stromal vascular fraction cells obtained by the three methods were significantly less than those by contact ultrasonic crushing method (P < 0.05). It is preferred to perform 20 minutes treatment by non-contact ultrasonic cell crusher followed by enzymatic separation. Figures and Tables | References | Related Articles | Metrics

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Inhibition of high mobility group box 1/nuclear factor-kappa B pathway reduces apoptosis in spinal cord astrocytes after oxygen-glucose deprivation/reoxygenation  Lü Cong, Sun Lin, Feng Haoyu, Ma Xun, He Yajun, Li Jisheng 2019, 23 (33):  5353-5359.  doi: 10.3969/j.issn.2095-4344.1811 Abstract ( 442 )   PDF (1009KB) ( 461 )   Save BACKGROUND: Spinal cord injuries triggers the release of high mobility group box 1 (HMGB1) from nerve cells to activate the nuclear factor-kappa B (NF-κB) by binding to cell membrane surface receptor, thereby inducing a series of pathological reactions, such as spinal cord edema or inflammation. However, little is reported on whether inhibition of HMGB1/NF-κB pathway could attenuate spinal cord astrocytes apoptosis after oxygen-glucose deprivation/reoxygenation (OGD/R). OBJECTIVE: To investigate the effect of HMGB1/NF-κB pathway on spinal cord astrocytes apoptosis after OGD/R. METHODS: Spinal cord astrocytes of newborn Sprague-Dawley rats (provided by the Laboratory Animal Center of Shanxi Medical University, China) were cultured in vitro and an OGD/R model was established. Spinal cord astrocytes were subjected to reoxygenation 6, 12, and 24 hours. Release of HMGB1 in the culture medium was detected by ELISA. The expression of HMGB1, Bcl-2 and Bax were detected by western blot and the cell survival rate was determined by MTT. The optimal reoxygenation time was then selected for the following experiments. Spinal cord astrocytes at passage 4 were divided into normal group, OGD6h/R24h group, OGD6h/R24h+ethyl pyruvate group, OGD6h/R24h+Bay 11-7082 group. After 24 hours of reoxygenation, the release of HMGB1 was detected by ELISA, the expression of HMGB1, NF-κB, Bcl-2 and BAX was analyzed by western blot, the survival rate of astrocytes was determined by MTT, and the apoptosis of astrocytes was measured by flow cytometry. RESULTS AND CONCLUSION: (1) The results showed that the best reoxygenation time was 24 hours, which was used for subsequent experiments. (2) Compared with the normal group, the release and expression of HMGB1 and NF-κB as well as the apoptotic rate of astrocytes were obviously increased in the OGD6h/R24h group (P < 0.05), while the survival rate of astrocytes and the ratio of Bcl-2/Bax were obviously declined in the OGD6h/R24h group (P < 0.05). Compared with the OGD6h/R24h group, the astrocyte survival rate and the ratio of Bcl-2/Bax were significantly raised (P < 0.05), while the expression of NF-κB and the apoptosis rate of astrocytes were remarkably decreased (P < 0.05) in the OGD6h/R24h+ethyl pyruvate and OGD6h/R24h+Bay 11-7082 groups. To conclude, the HMGB1/NF-κB signal pathway is involved in the regulation of apoptosis in spinal cord astrocytes after OGD/R. Figures and Tables | References | Related Articles | Metrics

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Increased expression of long-chain non-coding RNA LINC00511 in periodontitis promotes osteoclast proliferation Zhao Xiangyu, Zhang Guirong, Guo Chuanbo, Shi Chun, Wu Liuzhong 2019, 23 (33):  5360-5365.  doi: 10.3969/j.issn.2095-4344.1832 Abstract ( 430 )   PDF (785KB) ( 364 )   Save BACKGROUND: LINC00511 is a relatively new long-chain non-coding RNA (Lnc RNA). Studies have shown that lincRNA-ANRIL is closely related to the occurrence and development of periodontal disease. OBJECTIVE: To study the expression of LINC00511 in periodontitis, and to explore LINC00511 effects on osteoblast proliferation and differentiation. METHODS: The study protocol was approved by the Ethics Committee of Stomatology Hospital of Shenyang. Patients and their relatives were fully informed of study protocol and informed consent was signed prior to the inception of the trial. Periodontal ligament tissues were extracted from patients with periodontitis and patients undergoing orthodontic extraction (control group). The expression of LINC00511, tartrate-resistant acid phosphatase and cathepsin K in periodontitis patients was detected by real-time PCR. The third generation of osteoclast precursor cells RAW264.7 were induced to differentiate into osteoclasts and identified. LINC00511-siRNA was transfected into osteoclasts, and non-transfected osteoclasts were used as control. Transfection efficiency was detected by real-time PCR. RAW264.7 cells were cultured with 100 μg/L lipopolysaccharide for 0, 24, and 48 hours, and the expression of LINC00511 was detected. After LINC00511 transfection, proliferation and differentiation of osteoclasts were detected by cell counting kit-8 and tartrate-resistant acid phosphatase, respectively. RESULTS AND CONCLUSION: The levels of LINC00511, tartrate-resistant acid phosphatase and cathepsin K in human periodontitis samples were markedly higher than those in the control group. The expression of LINC00511 was time-dependently increased in osteoclasts after lipopolysaccharide treatment. Findings from fluorescence microscopy and real-time PCR showed that the expression of LINC00511 was significantly decreased after LINC00511-siRNA transfection compared with the control group (P < 0.05). LINC00511 promoted the proliferation and differentiation of osteoclasts. To conclude, the expression of LINC00511 is increased in periodontitis samples, and LINC00511 can promote the proliferation of osteoclasts. Figures and Tables | References | Related Articles | Metrics

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Porcine nucleus pulposus matrix induces differentiation of bone marrow mesenchymal stem cells into notochord-like cells Li Defang, Jiang Zengxin, Zeng Qingmin, Wu Jingping, Xie Xiaocheng 2019, 23 (33):  5366-5371.  doi: 10.3969/j.issn.2095-4344.1833 Abstract ( 347 )   PDF (784KB) ( 792 )   Save BACKGROUND: As notochord cells can develop resistance to a harsh microenvironment in the intervertebral disc, it may be a suitable cell source for the treatment of degenerative diseases of the intervertebral disc. Porcine nucleus pulposus contains a large number of notochord cells throughout the life, and various cytokines in the cell matrix can induce the differentiation of bone marrow mesenchymal stem cells into notochord-like cells. OBJECTIVE: To explore the effect of porcine nucleus pulposus matrix on the differentiation of bone marrow mesenchymal stem cells. METHODS: Porcine bone marrow mesenchymal stem cells were isolated, cultured and identified in vitro. Porcine nucleus pulposus powder was prepared, and suspended in the DMEM complete medium to prepare the DMEM medium containing porcine nucleus pulposus matrix. Then, the bone marrow mesenchymal stem cells were induced in the prepared medium. After 3 weeks of induction, Notochord cell marker genes, including brachyury, cytokeratin 8, and cytokeratin 18, were evaluated by RT-PCR. The study protocol was approved by the Animal Ethics Committee of Jinshan Hospital affiliated to Fudan University. RESULTS AND CONCLUSION: (1) Primary cultured bone marrow mesenchymal stem cells exhibited adherent growth. These cells had the ability of osteogenic and adipogenic differentiation under special conditions, and expressed CD90 and CD105. (2) Under the induction of porcine nucleus pulposus matrix, the cell morphology was changed, and the expression of brachyury, cytokeratin 8, and cytokeratin 18 was enhanced. To conclude, porcine nucleus pulposus matrix can induce the differentiation of bone marrow mesenchymal stem cells into notochord-like cells with notochord cell phenotype, which may provide a reliable cell source for the cell therapy of degenerative diseases of the intervertebral disc. Figures and Tables | References | Related Articles | Metrics

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Construction of circular RNA mmu_circ_Rab11a overexpression vector to transfect 293T cells Yuan Peiyan, Chen Lei, Xu Shuaimei, Tong Fangli, Xu Pingping 2019, 23 (33):  5372-5377.  doi: 10.3969/j.issn.2095-4344.1822 Abstract ( 732 )   PDF (886KB) ( 225 )   Save BACKGROUND: Rab11a plays an important role in the cell autophagy and proliferation, and circular RNA is involved in the regulation of biological processes by regulating the expression of parental genes. Therefore, whether mmu_circ_Rab11a also plays an important role in the process of cell autophagy and proliferation deserves further study. OBJECTIVE: To investigate the feasibility of circular RNA (mmu_circ_Rab11a) plasmid vector construction and transfection of 293T cells. METHODS: We constructed PLC5+mmu_circ_Rab11a overexpressed plasmid vectors, verified the recombinant plasmid by PCR and gene sequencing. mmu_circ_Rab11a overexpression vector was transiently transfected into 293T cells using Lipofectamine 3000 transfection reagent. Expression of mmu_circ_Rab11a gene in control, pLC5-ciR and mmu_circ_Rab11a overexpression groups was detected by RT-PCR, and PCR products were verified by Sanger sequencing. mmu_circ_Rab11a overexpression plasmid vector was transfected into MC3T3 cells and cell counting kit-8 was used to detect cell proliferation ability. RESULTS AND CONCLUSION: mmu_circ_Rab11a overexpression vector was successfully constructed, which could efficiently promote mmu_circ_Rab11a transcribed into 293T cells. Over-expression of mmu_circ_Rab11a could enhance the proliferation of MC3T3 cells. Our findings indicate that gene engineering technology can be used to construct mmu_circ_Rab11a overexpression vector, which is then transfected into 293T cells by liposomal transfection method to make efficient transcription of mmu_circ_Rab11a, laying an experimental foundation for further investigation on the biological function of mmu_circ_Rab11a. The proliferation of MC3T3 cells could be affected by regulating the expression of mmu_circ_Rab11a. Figures and Tables | References | Related Articles | Metrics

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Stem cell therapy for Alzheimer’s disease: research status and developmental trend Xu Gexin, Zhang Yunxia, Zhang Haiying 2019, 23 (33):  5378-5384.  doi: 10.3969/j.issn.2095-4344.1817 Abstract ( 724 )   PDF (834KB) ( 1258 )   Save BACKGROUND: Alzheimer’s disease is a degenerative brain disease, and there are no known drugs for curing Alzheimer’s disease. Stem cell transplantation provides a new therapeutic method for Alzheimer’s disease. OBJECTIVE: To reveal the theme, evolutionary path and research progress of stem cell therapy for Alzheimer’s disease, in a bid to provide reference for the research and clinical treatment of Alzheimer’s disease. METHODS: A computer search of CNKI, CBM, ISI Web of knowledge, and Embace was performed with the keywords of “Alzheimer’s disease” and “stem cells” + “Alzheimer’s disease,” in Chinese and English, respectively. We conducted a visualized knowledge mapping and literature review of stem cell therapy for Alzheimer’s disease using CiteSpace software. RESULTS AND CONCLUSION: The evolutionary path of research on stem cell therapy for Alzheimer’s disease is closely related to stem cell transplantation research. The main line of this research is single and prominent, which is developed and implemented based on the keywords of “Alzheimer’s disease - stem cells, neural stem cells - transplantation - bone marrow mesenchymal stem cells, mesenchymal stem cells, human umbilical cord mesenchymal stem cells, beta-amyloid - tissue engineering,” and the core domains composed by these keywords. Human stem cell clinical trials are ongoing in the early stage. The safety, efficacy and ethical issues of stem cells should be emphasized. The regulation of stem cell differentiation should become an issue of concern, and individualized stem cell treatment should be implemented as soon as possible.    Figures and Tables | References | Related Articles | Metrics

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Mesenchymal stem cells: present status and prospect for its application in peripheral nerve injury Cao Lizhi, Feng Naibo, Wang Juan, Chen Jiafeng 2019, 23 (33):  5385-5391.  doi: 10.3969/j.issn.2095-4344.1841 Abstract ( 658 )   PDF (721KB) ( 640 )   Save BACKGROUND: Mesenchymal stem cells have multi-directional differentiation potential and immunomodulatory properties. In recent years, mesenchymal stem cells have been favored by researchers in the repair of peripheral nerve injury. OBJECTIVE: To summarize the efficacy of mesenchymal stem cells in the repair of peripheral nerve injury in recent years. METHODS: The authors retrieved PubMed, ScienceDirect, Medline and CNKI databases for relevant articles published from January 2000 to February 2019. The key words were “peripheral nerve injury, mesenchymal stem cells, tissue engineering, exosomes, nerve guidance conduits, genetic engineering” in Chinese and English, respectively. Initially, 428 articles were retrieved, and finally 66 articles were included in result analysis. RESULTS AND CONCLUSION: Mesenchymal stem cells can be locally injected into the site of peripheral nerve injury, effectively promoting the growth of axons, inhibiting inflammatory reactions around the injured site, and providing a suitable microenvironment for nerve repair. Mesenchymal stem cells-derived exosomes can be used to effectively solve negative factors caused by cell proliferation and host immunity response. Mesenchymal stem cells combined with nerve conduit scaffolds achieve better neurological repair concurrently. Genetic engineering techniques can be targeted to modify mesenchymal stem cells to design ideal seed cells that are more available for repairing peripheral nerve injuries. In conclusion, mesenchymal stem cells have unique advantages in peripheral nerve repair, which is an ideal strategy for tissue engineering. Figures and Tables | References | Related Articles | Metrics

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Umbilical cord blood mesenchymal stem cells for treatment of tongue squamous cell carcinoma Zhang Xinyu, Wang Zhuhui, Xu Zhuqing, Zheng Jianjin 2019, 23 (33):  5392-5395.  doi: 10.3969/j.issn.2095-4344.1829 Abstract ( 349 )   PDF (566KB) ( 161 )   Save BACKGROUND: Tongue squamous cell carcinoma is one of the most common oral malignant tumors with strong local invasion, high lymphatic metastasis rate and poor prognosis. Umbilical cord blood mesenchymal stem cells have multidirectional differentiation potential. Recent studies have confirmed that they can inhibit malignant biological behaviors of lung cancer, liver cancer and other tumors. However, the role and specific mechanism of umbilical cord blood mesenchymal stem cells in tongue cancer remain unclear. OBJECTIVE: To review the research progress of umbilical cord blood mesenchymal stem cells in the treatment of tongue squamous cell carcinoma. METHODS: PubMed, WanFang and CNKI databases were retrieved for literatures about umbilical cord blood mesenchymal stem cells. The search terms were “umbilical cord blood mesenchymal stem cells, cancer cells,” “umbilical cord blood mesenchymal stem cells, tongue squamous cell carcinoma cells,” and “umbilical cord blood mesenchymal stem cells, migration, invasion” in Chinese and English, respectively. In total 33 articles were induced for result analysis. RESULTS AND CONCLUSION: Preliminary studies have shown that umbilical cord blood mesenchymal stem cells can inhibit the migration and invasion of tongue squamous cell carcinoma cells. Increasing evidence has confirmed that umbilical cord blood mesenchymal stem cells can migrate to the tumor site due to their tumor chemotaxis, and exert their effects by releasing various signal molecules, chemical factors, and cytokines. Therefore, umbilical cord blood mesenchymal stem cells are expected to provide a new treatment for tongue squamous cell carcinoma. Figures and Tables | References | Related Articles | Metrics

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Satellite glial cells in dorsal root ganglia: implication for pain regulation Zhang Xiaozhuo, Lü Tingting, Wang Zhaoqin, Weng Zhijun, Cui Yunhua, Zhang Fang, Zhao Min, Liu Huirong, Wu Huangan 2019, 23 (33):  5396-5403.  doi: 10.3969/j.issn.2095-4344.1840 Abstract ( 845 )   PDF (843KB) ( 2019 )   Save BACKGROUND: Satellite glial cells which are the main glial cell type in the dorsal root ganglia can interact and communicate with dorsal root neuron cell bodies through various approaches to be involved in the occurrence and regulation of chronic pain. Previous studies have focused on the sensitized neuronal cell bodies of satellite glial cells, and there is less concern about inhibitory regulation between them. So far there has been no research on their exchange as well as no discussion on their internal relationship. OBJECTIVE: To review the possible interaction and communication mechanisms between satellite glial cells and neurons in terms of structural morphology, ion channels, protein receptors and interactions between adjacent satellite glial cells. METHODS: PubMed, Web of Science, SinoMed, and CNKI were retrieved with the keywords of “pain, satellite glial cell, DRG, gap junction” for relevant articles published from January 2008 to February 2019. We also traced highly relevant references cited in the literature. Finally, 77 eligible studies were included. RESULTS AND CONCLUSION: In the dorsal root ganglia, satellite glial cells surround single neurons to form satellite glial sheathes. “Neuron-satellite glial cell” functional units are the base for mutual regulation between adjacent neurons. Majority of the studies have considered that satellite glial cells play an important role in the development and maintenance of chronic pain diseases; however, some studies have found the inhibitory regulation between satellite glial cells and neurons, which activates P2Y1 receptor and glutamate transporters to inhibit the occurrence of pain. Therefore, to regulate P2Y1 receptor and glutamate transporter activities in the dorsal root ganglia can be used as a new target for the treatment of pain. Figures and Tables | References | Related Articles | Metrics

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Bone morphogenetic protein 9: osteogenic induction mechanism and clinical application Zhu Zhengqing, Chen Xiangrun, Jia Fangteng, Huang Lanfeng 2019, 23 (33):  5404-5412.  doi: 10.3969/j.issn.2095-4344.1839 Abstract ( 431 )   PDF (777KB) ( 2159 )   Save BACKGROUND: Bone morphogenetic protein 9 has been proven to be the strongest osteogenic growth factor in the bone morphogenetic protein family. OBJECTIVE: To explore the research progress of bone morphogenetic protein 9 induced osteogenic mechanism and its application. METHODS: Web of Science, PubMed, WanFang and CNKI were searched using “bone morphogenetic protein9/BMP9, bone ingrowth, bone tissue engineering, osteogenic differentiation, cytokines” as key words for relevant articles published from 1989 to 2019. A comprehensive analysis and review was performed after removal of irrelevant and repetitive literature. RESULTS AND CONCLUSION: To date, bone morphogenetic protein 9 has been shown to be one of the most potent growth factors for inducing the osteogenic differentiation of mesenchymal stem cells in vitro and in vivo in the 14 bone morphogenetic protein family members. Moreover, bone morphogenetic protein 9 plays an important role in the repair of bone and cartilage damage and in promoting osteogenic differentiation. Bone morphogenetic protein 9 is also known as growth differentiation factor 2, and its mechanism underlying osteogenic induction is very complicated. Its signaling pathway involves various osteogenic signaling pathways, and various growth regulators are also involved in the entire osteogenic induction by bone morphogenetic protein 9. The osteogenic mechanism of bone morphogenetic protein 9 is different from the osteogenesis mechanism of other bone morphogenetic protein family members. In animal experiments, bone morphogenetic protein 9 can promote fracture healing, cartilage formation, and spinal fusion. Therefore, bone morphogenetic protein 9 has a great potential in basic research. Figures and Tables | References | Related Articles | Metrics