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02 April 2015, Volume 19 Issue 14 Previous Issue    Next Issue

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Optimized effect of connexin 43 gene silencing on the proliferation of fetal liver stem cells Zhang Zeng-guang, Qin Ming-fang 2015, 19 (14):  2133-2137.  doi: 10.3969/j.issn.2095-4344.2015.14.001 Abstract ( 266 )   PDF (622KB) ( 606 )   Save BACKGROUND: Fetal liver stem cells have the potential to differentiate into hepatocytes and bile duct cells, and participate in the repair and reconstruction of the liver, which is an important source of hepatocytes. But there are a little amount of fetal liver stem cells in human body, and how to obtain a certain number of high-purity fetal liver stem cells is currently a hot research. OBJECTIVE: To construct a siRNA carrier that can effectively inhibit the expression of connexin 43 (Cx43) in rat fetal liver stem cells, and to investigate the effect of Cx43 inhibition on the proliferation and cell cycle of fetal liver stem cells cultured in vitro. METHODS: Fetal liver stem cells were cultured by the suspension culture in vitro, siRNA sequences targeting Cx43 (Cx43-siRNA) and negative control sequence (NC-siRNA) were designed and synthesized. Then, rat fetal liver stem cells were transferred electrophoretically and divided into three groups: blank group, NC-siRNA group, Cx43-siRNA group. Real-time PCR and western blot were used to assess the knockdown efficiency. Cellular proliferation was determined by cell growth curve and cell counting kit-8 assay. The cell cycle was analyzed by flow cytometry. RESULTS AND CONCLUSION: After transfection, the Cx43 gene and protein expression levels were declined dramatically in the Cx43-siRNA, NC-siRNA and blank groups, and the cells grew faster. The number of cells at G0/G1 phase decrease, but the number of cells in S phase increased. There were significant differences between the groups (P < 0.05). Electrophoretic transfer of Cx43-siRNA can promote the proliferation of cultured fetal liver stem cells and optimize the cell culture. 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 全文链接： Figures and Tables | References | Related Articles | Metrics

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Bone mesenchymal stem cells with allogeneic bone to repair canine mandibular defects: detection of osteogenic ability   Jing Cai-xia, Liu Chang-kui, Tan Xin-ying, Luo Jin-chao, Hu Min 2015, 19 (14):  2138-2143.  doi: 10.3969/j.issn.2095-4344.2015.14.002 Abstract ( 316 )   PDF (938KB) ( 518 )   Save BACKGROUND: Allogeneic bone has anatomical appearance and biological features similar to autogenous bone, which is an excellent biological scaffold material. Mesenchymal stem cells originating from autogenous bone marrow have mutli-lineage differentiation potential, can differentiate into osteoblasts and chondrocyte, and thus can accelerate the formation of bone tissue and cartilage tissue. OBJECTIVE: To establish the osteogenic ability of allogeneic bone with autogenous bone marrow mesenchymal stem cells for repairing major mandibular defects. METHODS: The left mandibular teeth of 24 beagles were extracted, and at 2 months after wound healing, mandibular defects were made artificially. The beagles were divided into two groups: control group treated with lyophilized allogeneic bone, and experimental group with autogenous bone marrow mesenchymal stem cells and lyophilized allogeneic bone. Densitometry with CT and Micro-CT was conducted 4, 12, and 24 weeks after surgery. RESULTS AND CONCLUSION: Compared with the control group, the bone density of the mandible was significantly higher in the experimental group at 12 weeks after transplantation (P < 0.05). Over time, the bone densities in the two groups were both increased, but the bone density in the experimental group was always higher than that in the control group. Bone structure parameters were progressively increased or decreased in the two groups, especially in the experimental group. At 24 weeks after surgery, the degree of trabecular separation in regions of interest was higher in the experimental group than the control group (P < 0.05), but the bone volume fraction, number of trabecular bone, and bone trabecular thickness were significantly lower in the experimental group than the control group (P < 0.05). These findings indicate that bone marrow mesenchymal stem cells are capable of accelerating the reconstruction of allogeneic bones. 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 全文链接： Figures and Tables | References | Related Articles | Metrics

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Platelet-rich plasma accelerates the proliferation of bone marrow mesenchymal stem cells Xu Xiang, Yin He-ping 2015, 19 (14):  2144-2148.  doi: 10.3969/j.issn.2095-4344.2015.14.003 Abstract ( 353 )   PDF (1857KB) ( 477 )   Save BACKGROUND: Platelet-rich plasma contains a variety of stimulating factors, and can also raise the proteoglycan and collagen synthesis. OBJECTIVE: To observe the effect of platelet-rich plasma on the proliferation of goat bone marrow mesenchymal stem cells. METHODS: Blood samples were extracted from the jugular vein of Inner Mongolia Ximeng goats to harvest platelet-rich plasma using centrifugation method. Then, bone marrow was extracted from the goat’s ilium by puncture method to isolate and purify goat bone marrow mesechymal stem cells using density gradient centrifugation method. After that, primary cells at good state were cultured in L-DMEM complete medium containing 10%, 20%, 30% platelet-rich plasma or in simple L-DMEM complete medium. RESULTS AND CONCLUSION: Within 2-6 days of culture, cells in the platelet-rich plasma groups proliferated faster than those in the control group, and with the increasing of platelet-rich plasma concentration, the cells grew faster, with larger number and more mature morphology. At 4 days of culture, the cell doubling time was about 50, 35, 25 hours in the 10%, 20%, and 30% platelet-rich plasma groups, respectively. These findings indicate that goat platelet-rich plasma can dramatically promote the proliferation of bone marrow mesenchymal stem cells in a concentration-dependent manner. 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 全文链接： Figures and Tables | References | Related Articles | Metrics

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Treatment of osteoarthritis using colony-forming cells in stromal vascular fraction of adipose tissue Lv Pin-lei, Su Yue-han, Cao Yun, Wang Zheng 2015, 19 (14):  2149-2154.  doi: 10.3969/j.issn.2095-4344.2015.14.004 Abstract ( 382 )   PDF (2198KB) ( 841 )   Save BACKGROUND: Stromal vascular fraction digested from adipose tissue is a mixture of a variety of cells, and clone-like cell components may have the real ability to maintain the stemness of mesenchymal stem cells OBJECTIVE: To separate, passage and culture colony-forming cells in the stromal vascular fraction of adipose tissue, and to test its ability to repair the knee cartilage in animal models. METHODS: Stromal vascular fraction isolated from fresh adipose tissue was cultured to collect clone-like adherent cells that were subject to digestion and passage until the third generation. A rabbit model of osteoarthritis was established surgically, and the third generation of colony-forming cells were transplantated into the articular cavity of model rabbits. Model rabbits with no cell transplantation served as controls. Cartilage regeneration in the knee joint of model rabbits were observed and compared. RESULTS AND CONCLUSION: At 3 days after transplantation of stromal vascular fraction cells, clone-like cell colonies appeared in adherent cells; at 5 days, the amount of clone-like cell colonies and surrounding single cells were both increased. At the passage 3, the clone-like cell colonies were also visible, which were fusiform in shape. Gross observation and MRI examination showed that these colony-forming cells could promote cartilage repair in the joint cavity, increase secretion of synovial fluid, and help to control inflammation and narrow ulceration area. Experimental findings are beneficial for optimizing the isolation and culture of adipose-derived mesenchymal stem cells and provide a new way for the clinical treatment of osteoarthritis. 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 全文链接： Figures and Tables | References | Related Articles | Metrics

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Identification and differentiation of breast cancer stem cells under tumor microenvironment Zhang Shu-qing, Zhang Bo, Hong Liang, Zhou Yong-an, Zhao Liang 2015, 19 (14):  2155-2160.  doi: 10.3969/j.issn.2095-4344.2015.14.005 Abstract ( 334 )   PDF (2068KB) ( 520 )   Save BACKGROUND: Breast cancer stem cells have a greater impact on the occurrence and metastasis of breast cancer. Under simulated tumor microenvironment, we can better analyze the proliferation and differentiation of breast cancer stem cells. OBJECTIVE: To explore the tumor microenvironment effect on the differentiation of breast cancer stem cells. METHODS: Breast cancer cells and MCF-7 cells were primarily cultured in fibroblast supernatant and serum-free PCM-2 medium, and formation of breast cancer cells microspheres was observed. Proliferative ability of breast cancer cells was detected using MTT colorimetry, and the surface markers of breast cancer stem cells and epithelial-mesenchymal transition markers were measured using immunocytochemistry and RT-PCR methods. RESULTS AND CONCLUSION: The diameter of primary cell microspheres was larger in the serum-free PCM-2 medium than in the fibroblast supernatant, but the culture speed was faster in the fibroblast supernatant than the serum-free PCM-2 medium. At 3 days of primary culture, the expression of ALDH1 in primary cells was greatly higher in the serum-free PCM-2 medium than in the fibroblast supernatant. However, the expressions of E-cadherin and vimentin were up-regulated in the fibroblast supernatant than in the serum-free PCM-2 medium. In addition, the expressions of E-cadherin and vimentin in MCF-7 cells cultured in the fibroblast supernatant were up-regulated, while the expressions of ALDH1 and Oct-4 were downregulated. These findings indicate that the tumor environment has some certain effects on the growth and differentiation of breast cancer stem cells, and some cytokines secreted from fibroblast supernatant can promote the proliferation and differentiation of breast cancer stem cell microspheres to some extent. 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 全文链接： Figures and Tables | References | Related Articles | Metrics

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Expression of CD44+/C-myc+ cancer stem cells and its relationship with the prognosis of patients in colorectal tumors Ma Fa-ku, Wang Huan, Liu Bin, Yang Yan-li, Su Qin-jun, Qian Zhen, Dong Liang 2015, 19 (14):  2161-2166.  doi: 10.3969/j.issn.2095-4344.2015.14.006 Abstract ( 276 )   PDF (1973KB) ( 413 )   Save BACKGROUND: Tumor recurrence results from the incomplete removal of cancer stem cells with self-renewal characteristics, and then how to label and eliminate cancer stem cells becomes the key to cancer treatment. OBJECTIVE: To observe the morphology，distribution and number of CD44+/C-myc+ cells in colorectal cancer, and to explore the relationship between the expression and postoperative metastasis. METHODS: Pathological tissues from 150 patients with colorectal cancer were taken to prepare tissue microarray, in order to observe and count CD44+/C-myc+ cells by using immunohistochemical double staining. Patients were followed up through mobile phones , letters , and so on, and the relationship between the expression of CD44+/C-myc+ cells and postoperative metastasis were statistically recorded. RESULTS AND CONCLUSION: There was no CD44+/C-myc+ cells in normal tissue and little in adenoma. A small number of CD44+/C-myc+ cells distributed as dots or focal lesions in adenocarcinoma. The number of CD44+/C-myc+ cells was related to the degree of adenocarcinoma differentiation, depth of invasion, and lymph node metastasis (P < 0.05). The univariate analysis showed that the overall survival rate and progression-free survival rate were associated with the number of CD44+/C-myc+ cells, lymph node metastasis and Ducks staging in adenocarcinoma (P < 0.05). The multivariate analysis showed that the overall survival rate was related to CD44+/C-myc+ cell amount and the progression-free survival rate was related to CD44+/C-myc+ cell amount and the Ducks staging. Therefore, CD44+/C-myc+ cells are probably cancer stem cells, and Ducks staging and CD44+/C-myc+ cell amount are important prognostic factors for colorectal cancer. 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 全文链接： Figures and Tables | References | Related Articles | Metrics

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Enrichment of lung cancer stem cells and expression of related markers Chen Ping, Wang Jian 2015, 19 (14):  2167-2171.  doi: 10.3969/j.issn.2095-4344.2015.14.007 Abstract ( 437 )   PDF (1794KB) ( 648 )   Save BACKGROUND: Lung cancer stem cells are tightly related to the treatment and prognosis of lung cancer. We can provide more references for clinical diagnosis and treatment of lung cancer through the study on the tumorigenicity and surface markers of lung cancer stem cells. OBJECTIVE: To explore the enrichment methods for lung cancer stem cells and cellular tumorigenicity. METHODS: Lung cancer stem cells were induced in serum-free culture medium containing epidermal growth factor, insulin-like growth factor 1, and basic fibroblast growth factor. Then, the expressions of related surface markers were detected using immunofluorescence method. After that, mice were implanted subcutaneous with lung cancer stem cell spheres to understand the tumorigenicity of lung cancer stem cells. RESULTS AND CONCLUSION: Lung cancer stem cells under serum-free induction and culture were changed to sphere-forming cells, and the immunofluorescence detection showed that over 80% of sphere-forming cells were positive for CCSP, SP-C and OCT4. After transplantation of sphere-forming cells, the mice showed a high tumorigenicity. These findings indicate that sphere-forming cells are formed after serum-free suspension culture of lung cancer stem cells, which have a higher tumorigenicity. 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 全文链接： Figures and Tables | References | Related Articles | Metrics

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Transplantation of human umbilical cord mesenchymal stem cells in the treatment of systemic lupus erythematosus   Ruan Guang-ping, Yao Xiang, Liu Ju-fen, Wang Jin-xiang, Hu Yuan-yuan, Li Zi-an, Yang Jian-yong, Pang Rong-qing, Pan Xing-hua 2015, 19 (14):  2172-2178.  doi: 10.3969/j.issn.2095-4344.2015.14.008 Abstract ( 455 )   PDF (2333KB) ( 881 )   Save BACKGROUND: Systemic lupus erythematosus is an autoimmune disease characterized as an emergence of a variety of autoantibodies in serum and multi-system and multi-organ lesions. Currently, there is a lack of effective treatment options, and umbilical cord mesenchymal stem cells are a promising therapy for systemic lupus erythematosus based on cell biological roles. OBJECTIVE: To observe the therapeutic efficacy of human umbilical cord mesenchymal stem cell transplantation in the treatment of systemic lupus erythematosus in mice. METHODS: Human umbilical cord mesenchymal stem cells were isolated and cultured followed by labeling with DiR fluorescence. Experimental mice were divided into normal control group (C57BL mice), model control group (C57BL/lpr mice), low-, medium- and high-dose umbilical cord mesenchymal stem cell therapy groups (C57BL/lpr mice), with 10 mice in each group. Mice in the low-, medium- and high-dose groups were respectively injected 0.5×106, 1×106, 2×106 human umbilical cord mesenchymal stem cells, once a week, for 3 consecutive weeks. At the end of treatment, blood samples were collected to measure antinuclear antibody, anti-histone antibody, anti-double stranded DNA antibody changes; OPG and Foxp3 gene expression changes were detected by quantitative PCR method. RESULTS AND CONCLUSION: After treatment, the levels of anti-nuclear antibodies, anti-histone antibodies and anti-double stranded DNA antibodies in the peripheral blood of mice were all declined in the low-, medium- and high-dose groups, while the number of peripheral blood CD4+CD25+T cells was significantly elevated. OPG and Foxp3 gene expression was also increased dramatically in the low-, medium- and high-dose groups, which was similar to that in the normal control group and significantly different from that in the model control group (P < 0.01). Experimental findings demonstrate that after transplantation of human umbilical cord mesenchymal stem cells, all relevant indicators in C57BL/lpr mice recovered to the normal levels, and the high-dose treatment group had the most obvious effect. 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 全文链接： Figures and Tables | References | Related Articles | Metrics

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Human umbilical cord mesenchymal stem cells via intramuscular injection influence the expression of cytokines related to dilated cardiomyopathy in rats   Jiang Yan-jie, Mao Cheng-gang, Ning Xian-feng, Li Rong, Li Zi-pu 2015, 19 (14):  2179-2185.  doi: 10.3969/j.issn.2095-4344.2015.14.009 Abstract ( 280 )   PDF (2242KB) ( 444 )   Save BACKGROUND: Studies have shown that intramuscular transplantation of xenogeneic umbilical cord mesenchymal stem cells in a certain dose range is safe and reliable, and it also confirm that this approach is equally safe and effective for heart failure in rats with dilated cardiomyopathy. OBJECTIVE: To explore the effect of human umbilical cord mesenchymal stem cells through intramuscular injection on the cytokine expression in adriamycin-induced dilated cardiomyopathy (DCM) rats. METHODS: Totally 160 rats were randomly divided into control group (n=20) and DCM group (n=140). Rats in the DCM group were administered adriamycin intraperitoneally to establish DCM model. The DCM rats were randomly subdivided into model control group (served as model group), cell supernatant group, the low-dose mesenchymal stem cell group (served as low-dose group), the middle-dose mesenchymal stem cell group (served as middle-dose group), and the high-dose mesenchymal stem cells group (served as high-dose group). Secondary injection was performed at 4 weeks after first injection. RESULTS AND CONCLUSION: The ELISA test showed that the serum levels of vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), leukemia inhibitor factor (LIF) and granulocyte macrophage colony stimulating factor (GM-CSF) were higher in the model group than the control group before and after intramuscular injection (P < 0.05). After intramuscular injection, the levels of HGF, LIF, GM-CSF and VEGF in the low-dose group were increased significantly (P < 0.05), which were significantly higher than those in the model group (P < 0.05). The level of LIF in the middle-dose group was significantly elevated after injection (P < 0.05), while there were no significant differences in HGF, VEGF and GM-CSF levels in the high-dose group before and after intramuscular injection (P > 0.05). Both the immunohistochemical and RT-PCR results showed that the expressions of insulin-like growth factor-1, VEGF and HGF were increased in all the DCM rats as compared with the control group, which were increased most in the middle-dose group. These findings indicate that low-dose and middle-dose human umbilical cord mesenchymal stem cells intramuscular injection can increase the serum levels of HGF, LIF, GM-CSF, VEGF and the expressions of IGF-1, HGF and VEGF in the myocardium of DCM rats. 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 全文链接： Figures and Tables | References | Related Articles | Metrics

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Umbilical cord blood mesenchymal stem cells transplantion for polymyositis/dermatomyositis: variation of Th cytokines Lai Qin, Yu Lian, Qiu Yong-rong, Chen Long-tian, Huang Jian-qing, Li Yu-min, Zhang Li, Wu Wei-hao, Wu Ai-yu, Luo Bi-hua, Tian Pan 2015, 19 (14):  2186-2191.  doi: 10.3969/j.issn.2095-4344.2015.14.010 Abstract ( 389 )   PDF (2156KB) ( 448 )   Save BACKGROUND: In recent years, the application of stem cells to treat autoimmune diseases has become a hot spot. But, studies on umbilical cord blood mesenchymal stem cells transplantation for the treatment of polymyositis/dermatomyositis are rarely reported. OBJECTIVE: To explore the immunologic mechanism of Th cytokines on the occurrence and development of polymyositis/dermatomyositis by observing the changes in serum interferon-γ, interleukin-4 and interleukin-17 in patients after umbilical cord blood mesenchymal stem cells transplantation. METHODS: Eighty-one polymyositis/dermatomyositis patients were selected and divided into conventional therapy group (n=44) undergoing glucocorticoid and immunosuppressants therapy and cell transplantation group (n=37) undergoing intravenous infusion of umbilical cord blood mesenchymal stem cells at a density of (3.5-5.2 )×107. Dosing regimen was same in the two groups. After follow-up of 1, 3, 6 months, the changes of creatine kinase and myodynamia were evaluated; after follow-up of 3 and 6 months, lung imaging was evaluated; in the cell transplantation group, interferon-γ, interleukin-4 and interleukin-17 levels were detected before treatment and at 3 and 6 months after treatment. RESULTS AND CONCLUSION: At 1, 3, 6 months after treatment, the creatine kinase level was significantly decreased, and the muscle force grade was significantly increased in both groups (both P < 0.001). Compared with the conventional therapy group, the creatine kinase level was lower and the muscle force grade was higher in the cell transplantation group (both P < 0.001). Results from lung imaging test showed a remarkable improvement after cell transplantation, and it indicated that umbilical cord blood mesenchymal stem cells transplantation had good stability. At 6 months after transplantation, the level of interferon-γ was significantly increased, while the interleukin-4 level was decreased significantly (both P < 0.01); at 3, 6 months after cell transplantation, the levels of interleukin-17 were significantly decreased (P < 0.01). Levels of interleukin-4 and interleukin-17 were positively correlated with the level of creatine kinase at 6 months after cell transplantation (r=0.467, 0.488, both P < 0.05), but there was no obvious correlation between the levels of interferon-γ and creatine kinase (r=0.213, P > 0.05). These findings indicate umbilical cord blood mesenchymal stem cells transplantation combined with glucocorticoid and immunosuppressants therapy can adjust immune network effects and improve the immune tolerance in polymyositis/dermatomyositis patients, which is safe and effective. 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 全文链接： Figures and Tables | References | Related Articles | Metrics

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Transplantation of human umbilical cord derived-mesenchymal stem cells by different ways for the treatment of spinal cord injury     Liu Yu-liang, Li Jun, He Yu-qin, Zhuo Feng, Wei Kai-bin 2015, 19 (14):  2192-2198.  doi: 10.3969/j.issn.2095-4344.2015.14.011 Abstract ( 375 )   PDF (900KB) ( 546 )   Save BACKGROUND: Currently, human umbilical cord derived-mesenchymal stem cells are mainly for local transplantation, which has some shortcomings, such as large trauma, bleeding, complications, that limit its widespread application in clinical practice. OBJECTIVE: To investigate the feasibility of intravenous transplantation of human umbilical cord derived-mesenchymal stem cells for repair of spinal cord injury. METHODS: Eighty Wistar rats with spinal cord hitting were divided into five groups: blank control group with no transplantation (n=10), DMEM local transplantation group (n=15), DMEM intravenous transplantation group (n=15), cell local transplantation group (n=20), cell intravenous transplantation group (n=20). The functional recovery of spinal cord injury was observed with Basso, Beattie and Bresnahan scores at regular time as well as hematoxylin-eosin staining and immunohistochemistry staining. RESULTS AND CONCLUSION: During 1 day to 2 weeks after transplantation, there was no significant difference in the Basso, Beattie and Bresnahan scores between the five groups; within 4-12 weeks after transplantation, the Basso, Beattie and Bresnahan scores were significantly higher in the two cell transplantation groups than the other three groups, but there was no difference between these two cell transplantation groups (P > 0.05). Histological observation showed that the number of voids and glial scars was less in the cell local transplantation group and cell intravenous transplantation group compared with the other three groups, and there was also no difference between the two cell transplantation groups. These results indicate that the intravenous transplantation of human umbilical cord derived-mesenchymal stem cells is similar to the local transplantation in the repair of acute spinal cord injury, which is simple and avoids secondary injuries and various complications. It is recommended that this method provide a new approach for cell transplantation. 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 全文链接： Figures and Tables | References | Related Articles | Metrics

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Oxidative stress response in diabetic nephropathy rats following injection of embryonic stem cells via the tail vein Fan Zhi-gang, Fan Hong-liang 2015, 19 (14):  2199-2204.  doi: 10.3969/j.issn.2095-4344.2015.14.012 Abstract ( 380 )   PDF (774KB) ( 496 )   Save BACKGROUND: Occurrence and development of diabetic complications is closely related to the severity of oxidative stress imbalance in the body. OBJECTIVE: To investigate the effect of embryonic stem cells on oxidative stress response of rats with diabetic nephropathy． METHODS: Primarily cultured rat embryonic stem cells were observed for cell morphology and surface antigen detection. Sprague-Dawley rats were divided into experimental group (two injections of embryonic stem cells via the tail vein), model group (injection of the same volume of PBS), and normal control group (with no modeling, intraperitoneal injection of sodium citrate-citrate buffer). In the former two groups, the rats were intraperitoneally injected sodium citrate-citrate buffer diluted streptozotocin to establish diabetic nephropathy models before treatment. At 5 weeks after the last injection, blood glucose level, renal function indicators (urine protein/urine creatinine, blood urea nitrogen and serum creatinine) were tested in each group; contents of malondialdehyde and protein carbonyl were detected in the kidney; the expression level of superoxide dismutase was detected by western blot assay. RESULTS AND CONCLUSION: The embryonic stem cells were oval or round, with clear boundary and good refraction, and highly expressed Oct-4 and SSEA-1. Compared with the control group, renal biochemical indicators, malondialdehyde and protein carbonyl contents were significantly increased, while the expression level of superoxide dismutase was decreased dramatically in the model group and experimental group (P < 0.05); compared with the model group, the renal biochemical indicators, malondialdehyde and protein carbonyl contents were dropped significantly in the experimental group, but the expression of superoxide dismutase was significantly rebounded (P < 0.05). Taken together, embryonic stem cells can reverse the occurrence and development of diabetic nephropathy by inhibiting oxidative stress in progress. 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 全文链接： Figures and Tables | References | Related Articles | Metrics

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Hyperbaric oxygen combined with Schwann cells transplantation for spinal cord injury in rats: electrophysiological and functional changes of the hind limbs   Wang Guo-xi, Wang Guo-qian, Zhang Shu-quan 2015, 19 (14):  2205-2210.  doi: 10.3969/j.issn.2095-4344.2015.14.013 Abstract ( 381 )   PDF (812KB) ( 509 )   Save BACKGROUND: Hyperbaric oxygen therapy can improve the microenvironment of the injured spinal cord, and hyperbaric oxygen combined with Schwann cell transplantation is expected to improve the therapeutic efficacy on spinal cord injury. OBJECTIVE: To investigate the effect of Schwann cell transplantation plus hyperbaric oxygen on the neural functional recovery of rats with spinal cord injury. METHODS: A total of 80 female SD rats with spinal cord injury were randomized into 4 groups, with 20 in each group: blank control group, injection of L-DMEM via the tail vein at 6 hours after modeling; cell transplantation group, injection of 3×106 Schwann cell suspension via the tail vein at 6 hours after modeling; hyperbaric oxygen group, hyperbaric oxygen therapy at 1 hour after modeling; combination group, combined therapy of Schwann cell transplantation and hyperbaric oxygen. Inclined plane test, modified Tarlov score, Basso-Beattie-Bresnahan score for motor function evaluation of rat hind limbs were performed and measured at 1, 3 days, 1, 2, 3, 4 weeks after treatment. SRY gene expression in the spinal cord was measured at 4 weeks after transplantation using PCR method. Horseradish peroxidase tracer and electroneurophysiology detection was done at 8 weeks after transplantation. RESULTS AND CONCLUSION: The motor function of the lower limbs was better in the combination group than the cell transplantation and hyperbaric oxygen groups, as well as better in the cell transplantation group and hyperbaric oxygen groups than the blank control group. SRY expression was detected in the cell transplantation group and combination group, but not in the blank control group and hyperbaric oxygen group. The number of nerve fibers positive for horseradish peroxidase was higher in the combination group than the cell transplantation and hyperbaric oxygen groups followed by the blank control group, and there were significant differences between different groups (P < 0.01). In addition, the latencies and amplitudes of somatosensory evoked potential and motor evoked potential in the combination group were also better than those in the other groups (P < 0.05 or P < 0.01). These findings indicate that the combined therapy of Schwann cell transplantation and hyperbaric oxygen can promote the synaptic regeneration, improve limb motor function and electrophysiological function in rats with spinal cord injury, which is superior to hyperbaric oxygen or Schwann cell transplantation alone. 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 全文链接： Figures and Tables | References | Related Articles | Metrics

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Bone marrow mesenchymal stem cell transplantation for treatment of emphysema: intravenous versus intratracheal approach Zhao Xiao-jian, Lu Cai-ping, Chu Wei-wei, Zhang Ya-xiao, Zhang Bing, Zhen Qiang, Tan Guo-liang, Wang Ren-feng, Liu Jia-bao, Wu Lin 2015, 19 (14):  2211-2215.  doi: 10.3969/j.issn.2095-4344.2015.14.014 Abstract ( 401 )   PDF (760KB) ( 394 )   Save Figures and Tables | References | Related Articles | Metrics

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Intraarticular injection of autologous bone marrow mesenchymal stem cells for mild-to-moderate osteoarthritis   Liang Jian-ji, He Zhi-yong, Liu Kang, Li Xiao-ling, Cheng Wei-min, Yu Xin-ping, Chen Er-dong 2015, 19 (14):  2216-2223.  doi: 10.3969/j.issn.2095-4344.2015.14.015 Abstract ( 456 )   PDF (1127KB) ( 630 )   Save BACKGROUND: Increasing evidence collected from animal experiments or laboratories shows that bone mesenchymal stem cells possess potent immunosuppression and anti-inflammation effects and cartilage regenerative capability. The microenvironment in human knee joint of osteoporosis is more complex and involves lots of bioactive factors and immunologic mechanisms. OBJECTIVE: The analyze the therapeutic effects of intra-articular injection of autologous bone marrow mesenchymal stem cells on mild-to-moderate osteoporosis, and to investigate the mechanisms for anti-inflammation, immunoregulation and reversion of cartilage degradation. METHODS: About 15 mL bone marrow was aspired from 26 patients with mild-to-moderate osteoporosis and taken to the laboratory where bone marrow mesenchymal stem cells were isolated and characterized in terms of some surface markers by a flow cytometer, and the ability of osteogenic and adipogenic differentiation was analyzed. The bilateral knees of each patient were divided into two groups at random. The experiment group were treated with autologous bone marrow mesenchymal stem cells by intra-articular injection (2×107 cells), while the control group injected the same volume of control medium without bone marrow mesenchymal stem cells. Western Ontario and McMaster Universities Osteoarthritis Index was used to estimate the function of the knee joints before and after the treatment. We collected the joint fluid before, 2 and 4 weeks post treatment, and then measured the production of interleukin-1, interleukin-10, tumor necrosis factor-α, cartilage oligomeric matrix protein using ELISA. RESULTS AND CONCLUSION: According to the standardized culture-expansion protocol, a sufficient number of bone marrow mesenchymal stem cells (more than 2×107 passage 3 cells) were obtained for intra-articular injection. The bone marrow mesenchymal stem cells isolated from patients were positive for CD105, CD29 and negative for CD45, CD34, and had the fair osteogenic and adipogenic capacities. The function of the knee joints was improved obviously after treatment. In the experimental group, the secretion of both interleukin-1, tumor necrosis factor-α and cartilage oligomeric matrix protein in the joint fluid was suppressed, while the interleukin-10 level was up-regulated compared to the control group. The results suggest that intra-articular injection of autologous bone marrow mesenchymal stem cells can exert good effect in mild-to-moderate osteoporosis patients. Furthermore, bone marrow mesenchymal stem cells via intra-articular injection can function through anti-inflammation and reversion of degradation of the articular cartilage, which is a new promising approach for treating mild-to-moderate osteoarthritis. 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 全文链接： Figures and Tables | References | Related Articles | Metrics

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Nerve growth factor-modified adipose derived stem cells for repair of spinal cord injury   Wang Yong, Zhao Wei, Feng Jian-zhou, Chen Xiao-chun 2015, 19 (14):  2224-2229.  doi: 10.3969/j.issn.2095-4344.2015.14.016 Abstract ( 329 )   PDF (1904KB) ( 365 )   Save BACKGROUND: Gene-modified stem cells can increase the secretion of peptides and full-length proteins to protect spinal cord injury and promote recovery of neuronal function, which thus become a research hotspot in recent years. OBJECTIVE: To investigate the effect of nerve growth factor-modified adipose derived stem cells in repairing spinal cord injury in rats. METHODS: Adipose derived stem cells were primarily cultured by adherent culture method and cell surface markers were detected by immunofluorescence method, while spinal cord injury models were set by modified Allen method. Nerve growth factor plasmid was transfected into adipose derived stem cells with Lipofectamine2000 and the expression of nerve growth factor was detected by real-time PCR and western blot. The modified adipose derived stem cells intervened by nerve growth factor were injected into the injured part of spinal cord injury rat models. Basso-Beattie-Bresnahan score was used to evaluate the repairing effect. Models rats were sacrificed at 3 weeks after cell transplantation. Real-time PCR and western blot were used to testify nerve growth factor expression in the injured spinal segment after cell transplantation. RESULTS AND CONCLUSION: Adipose derived stem cells were successfully cultured primarily, and positive for CD29 and CD44; the mRNA and protein expression of nerve growth factor was elevated after plasmid transfection. The Basso-Beattie-Bresnahan score was elevated after transplantation of adipose derived stem cells intervened by nerve growth factor modification compared to control group; and the expression of nerve growth factor in the injured segment of the spinal cord was up-regulated detected by real-time PCR and western blot. These findings indicate that the nerve growth factor-modified adipose derived stem cells have repairing effects on spinal cord injury in rats. 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 全文链接： Figures and Tables | References | Related Articles | Metrics

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Ultrastructure and phagocytotic function of human placental mesenchymal stem cells   Sha Wen-qiong, She Rui-lian, Wang Zi-neng, Ke Ru 2015, 19 (14):  2230-2235.  doi: 10.3969/j.issn.2095-4344.2015.14.017 Abstract ( 358 )   PDF (2148KB) ( 560 )   Save BACKGROUND: Placental mesenchymal stem cells with rich sources are similar to bone marrow mesenchymal stem cells in terms of morphology, surface markers and differentiation potential, which are one of ideal mesenchymal stem cells in human body. However, there are few studies addressing the ultrastructure and phagocytotic function of human placental mesenchymal stem cells and its physiological role in the the placenta has been little explored. OBJECTIVE: To investigate the ultrastrcture and phagocytotic function of placental mesenchymal stem cells. METHODS: Placental mesenchymal stem cells obtained from five placentae of normal pregnancy were cultured in vitro and observed for ultrastructure under transmission electron microscope. The fluorescent beads were added in the supernatant for 3 hours, and then the phagocytosis of placental mesenchymal stem cells was evaluated by flow cytometry. RESULTS AND CONCLUSION: Under the transmission electron microscope, placental mesenchymal stem cells had large nuclei with prominent nucleoli. In the cytoplasm, a plenty of rough endoplasmic reticula was seen, dilated or stacked. The cytoplasm was also rich in Golgi apparatus and lysosomes. The cell surfaces were covered by microvilli. The intercellular junctions could be seen occasionally. A part of cells from these five samples could phagocytose fluorescence beads, which ranged from 49.6% to 18.4%. The ultrastructural characteristics of placental mesenchymal stem cells suggested these cells were active to synthesize and secrete proteins and had phagocytotic function, indicating placental mesenchymal stem cells may play a role in keeping the balance of micro-environments and clean the foreign substances in the placenta.   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 全文链接： Figures and Tables | References | Related Articles | Metrics

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Osteogenic differentiation of pluripotent stem cells induced by akermanite extracts Du Qing-hua, Cao Jun-kai, Dong Xi-xi, E Ling-ling, Wei Li-jun 2015, 19 (14):  2236-2242.  doi: 10.3969/j.issn.2095-4344.2015.14.018 Abstract ( 348 )   PDF (2303KB) ( 448 )   Save BACKGROUND: Akermanite belongs to silicate bioactive ceramics, with degradation in vivo, and its ionic products can induce osteogenic differentiation, which is a good choice for bone tissue engineering scaffold. OBJECTIVE: By studying the different concentrations of akermanite extracts on the proliferation and osteogenic differentiation of pluripotent stem cells, to determine the optimum concentration of akermanite extract to inducing the osteogenic differentiation of pluripotent stem cells. METHODS: MTT assay was used to detect the proliferation of pluripotent stem cells cultured in different concentrations of akermanite extracts (1/2, 1/4, 1/8, 1/16, 1/32). After cultured with the extracts for 7, 14, 21 days, the culture supernatants were collected to detect the levels of alkaline phosphatase, osteocalcin, type I collagen. RESULTS AND CONCLUSION: The MTT assay showed that the proliferation of pluripotent stem cells was increased in a concentration-dependent manner after induction with akermanite extracts. The pluripotent stem cells proliferated obviously at 3 days after induction, and then weaken at 7 days, but there was no difference at 3 and 5 days after induction. At 7 days after induction, the 1/4 extract had the best effect on promoting osteogenic differentiation of pluripotent stem cells; the levels of alkaline phosphatase and osteocalcin were increased with time, especially after induction with the 1/4 extract; but there was no expression of type I collagen. At 14 and 21 days after induction, the levels of alkaline phosphatase, osteocalcin, type I collagen were highest in the 1/4 extract group. These findings indicate that the 1/4 akermanite extract (Ca 2.37 mmol/L, Mg 1.12 mmol/L, Si 1.05 mmol/L) is the optimum to promote the osteogenic differentiation of pluripotent stem cells. 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 全文链接： Figures and Tables | References | Related Articles | Metrics

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Microfracture technique plus bone marrow mesenchymal stem cell transplantation for repair of articular cartilage injury of the knee   Hu Zuo-hong, Wang Yu-long, Cai Zheng-dong, Chen Yu-quan, Xia Yan 2015, 19 (14):  2243-2249.  doi: 10.3969/j.issn.2095-4344.2015.14.019 Abstract ( 452 )   PDF (1055KB) ( 559 )   Save BACKGROUND: It has been an urgent problem of how to promote cartilage repair of the knee and shorten the total course through a tissue engineering approach. Fortunately, microfracture plus stem cell transplantation may open up a new path for this issue. OBJECTIVE: To investigate the clinic feasibility of arthroscopic microfracture technique plus stem cell transplantation for repair of articular cartilage injury of the knee. METHODS: From October 2010 to March 2012, a total of 16 patients with articular cartilage injury of the knee were enrolled, including 12 males and 4 females, with the average age of 38.6 years (16-52). All cases of cartilage injury were confirmed by arthroscopy. Autologous bone marrow was extracted from patients at 2 weeks before treatment to isolate, culture and amplify bone marrow mesenchymal stem cells in vitro. The cell culture solution of 3-5 mL (about 107 cells) was harvested. The articular cavity was clean by arthroscopy and microfracture technique was performed at the area of cartilage injury that was then covered with hemostatic gauze through a minimally invasive incision and the prepared bone marrow mesenchymal stem cells were injected. The knee was bandaged with the elastic bandage after aspirating the joint cavity effusion by vacuum suction. Functional exercises were performed early by CPM.  RESULTS AND CONCLUSION: After follow-up of 4-18 months, there were 13 cases of excellent, 2 cases of valid and 1 case of ineffective. According to Lysholm knee scores, the average scores were improved from 42 points (33-67 points) to 89 points (75-99 points) at 4 weeks after treatment. The function was satisfied and all patients were followed up without recurrence or worse. Under the arthroscopy, the combination of microfracture technique and autologous bone marrow mesenchymal stem cell transplantation is proved to be effective for articular cartilage injury of the knee and it can notably improve the clinic symptoms and recover the function of the knee. 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 全文链接： Figures and Tables | References | Related Articles | Metrics

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Human telomerase reverse transcriptase gene-transfected effects on biological characteristics of Schwann cells   Liu Lin-lin, Deng Wei-min 2015, 19 (14):  2250-2254.  doi: 10.3969/j.issn.2095-4344.2015.14.020 Abstract ( 397 )   PDF (791KB) ( 383 )   Save BACKGROUND: Studies have shown that genetically modified Schwann cells can survive for a longer time in vivo, and promote nerve regeneration and functional recovery. OBJECTIVE: To transfect human telomerase reverse transcriptase (hTERT) gene into rat Schwann cells cultured in vitro via PLXSN vector, and to detect the telomerase activity and biological characteristics of Schwann cells. METHODS: Schwann cells from Wistar rats were cultured in vitro and transfected by PLXSN vector with (hTERT group) or without hTERT (empty vector group). Normal Schwann cells were selected as control group. RT-PCR and western blot methods were used to detect the hTERT protein and mRNA levels in Schwann cells, and flow cytometry was used to measure the cell cycle distribution. Cell growth was observed by cell growth curve and MTT colorimetric method. RESULTS AND CONCLUSION: At 48 hours after transfection, the mRNA and protein expressions of hTERT were remarkably seen in Schwann cells. Compared with the control and empty vector groups, the cells grew faster, the number of cells at G0/G1 phase was reduced, but the number of S phase cells was increased in the hTERT group (P < 0.05). These findings indicate that PLXSN vector-mediated hTERT transfection of Schwann cells can significantly improve the activity of telomerase in Schwann cells as well as promote the proliferation of Schwann cells cultured in vitro. 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 全文链接： Figures and Tables | References | Related Articles | Metrics

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Bone morphogenetic protein 9-induced osteogenic differentiation of dental follicle cells in vitro   Wu Yan, Huang Lan 2015, 19 (14):  2255-2260.  doi: 10.3969/j.issn.2095-4344.2015.14.021 Abstract ( 340 )   PDF (2091KB) ( 452 )   Save BACKGROUND: Bone morphogenetic protein 9 is proved to promote the osteogenic differentiation of various kinds of stem cells, but whether it can induce the osteogenic differentiation of dental follicle cells in vitro is yet unclear. OBJECTIVE: To investigate whether bone morphogenetic protein 9 can induce the osteogenic differentiation of rat dental follicle cells in vitro. METHODS: Purified rat dental follicle cells at passage 3 were transfected with bone morphogenetic protein 9 adenovirus. Then, alkaline phosphatase activity, calcium deposition and expression of osteogenesis-related factors at mRNA and protein levels were detected in the dental follicle cells. RESULTS AND CONCLUSION: After transfection with bone morphogenetic protein 9, the dental follicle cells showed continuously enhanced alkaline phosphatase activities and obviously enhanced calcium deposition. Real-time PCR results demonstrated that the mRNA expressions of alkaline phosphatase, osteocalcin, bone sialoprotein, osteopontin and core binding factor were increased significantly. The western blot assay showed that the expression of osteopontin enhanced in the dental follicle cells after transfection with bone morphogenetic protein 9. In summary, bone morphogenetic protein 9 can induce the osteogenic differentiation of dental follicle cells. 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 全文链接： Figures and Tables | References | Related Articles | Metrics

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Expression pattern of ten-eleven translocation family during differentiation of human dental pulp cells Rao Li-jia, Li Qi-meng, Li Jin-ling, Xu Qiong 2015, 19 (14):  2261-2266.  doi: 10.3969/j.issn.2095-4344.2015.14.022 Abstract ( 363 )   PDF (1806KB) ( 499 )   Save BACKGROUND: Ten-eleven translocation (TET) family proteins are recently discovered DNA dioxygenases that convert methylcytosine to hydroxymethyl cytosine, which is essential for regulating cell proliferation and differentiation, but the expression pattern of TET family proteins in human dental pulp cells is still unclear. OBJECTIVE: To investigate the expression pattern of TET family proteins during the differentiation of human dental pulp cells. METHODS: Cellular distribution and expression of TET family proteins were determined by immunofluorescence in human dental pulp cells that were cultured and isolated using digestion method. The protein levels of TETs during cell passage (P1-P7) were detected with western blot assay, and their potential changes during odontogenic induction (7 and 14 days) were confirmed using real-time quantitative PCR and western blot analyses at mRNA and protein levels, respectively. RESULTS AND CONCLUSION: All TETs were expressed in the nucleus and the cytoplasm of human dental pulp cells During serial cell passage, TET1 protein expression was increased until the 6th passage, TET2 significantly increased at the 2nd and 3rd passages and then decreased (P < 0.05), and TET3 showed no statistically significant change (P > 0.05). Both mRNA and protein expression levels of all TETs were elevated during odontogenic induction (P < 0.05). These results indicated that TETs may contribute to cell differentiation of human dental pulp cells. 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 全文链接： Figures and Tables | References | Related Articles | Metrics

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Regulatory effects of warming yang and invigorating qi treatment on the inflammatory balance and genetic stability of bone marrow mesenchymal stem cells under tumor microenvironment  Gao Zhuo-yue, Liu Yong-qi, He Jian-xin, Wu Zhi-wei, Luo Ya-li, Su Yun, Zhang Li-ying, Zhang Qi, Wu You-ming, Zhou Ni-na 2015, 19 (14):  2267-2272.  doi: 10.3969/j.issn.2095-4344.2015.14.023 Abstract ( 307 )   PDF (2538KB) ( 532 )   Save BACKGROUND: How to further definite and prevent the genetic instability of bone marrow mesenchymal stem cells in tumor microenvironment has increasingly become a key problem for its clinic application. Meanwhile, increasing studies focus on the reciprocal causation relationship between uncontrolled inflammation and tumors. OBJECTIVE: To analyze the changes of inflammation-related signaling pathways and genetic stability in bone marrow mesenchymal stem cells under the tumor microenvironment, and meanwhile, to investigate the influence and mechanism of “warming yang and benefiting qi” method on inflammatory signaling pathways and the genetic stability of bone marrow mesenchymal stem cells in tumor microenvironment, based on the guidance of the traditional Chinese Medicine theories “warming yang and tonifying kidney, benefiting qi and raising yang, strengthening healthy and discarding evil to eliminate pathogens”. METHODS: A computer-based online search of PubMed, CNKI and VIP was performed for relevant articles with the keywords of “bone marrow mesenchymal stem cells, inflammatory balance, replenishing qi, warming yang, strengthening shen, elevate yang, tumor, cancer, yang can transform qi, yin shaping up body, genetic stability” in English and Chinese, respectively. Screened literatures were evaluated strictly according to the inclusion and exclusion criteria, and finally 42 articles were included in result analysis. RESULTS AND CONCLUSION: Under physical and chemical induction or tumor microenvironment, bone marrow mesenchymal stem cells can promote tumor proliferation, invasion and metastasis. In addition, bone marrow mesenchymal stem cells can be induced to differentiate into malignant cells or tumor associating fibroblasts, followed by genetic instability, in tumor microenvironment. Inflammatory microenvironment plays an important role in regulating inflammation-related signals and genetic stability of bone marrow mesenchymal stem cells. Chinese traditional medicines functioning as “warming yang and replenishing qi” can restore the genetic stability of bone marrow mesenchymal stem cells in tumor or chemical microenvironment, based on the guidance of the traditional Chinese Medicine theories of “warming yang and tonifying kidney, benefiting qi and raising yang, strengthening healthy and discarding evil to eliminate pathogens”. 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 全文链接： Figures and Tables | References | Related Articles | Metrics

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In vitro culture of embryos and establishment of embryonic stem cell lines Wang Fang, Chen Shao-wei 2015, 19 (14):  2273-2277.  doi: 10.3969/j.issn.2095-4344.2015.14.024 Abstract ( 365 )   PDF (593KB) ( 393 )   Save BACKGROUND: The successful establishment of human embryonic stem cell lines in vitro is of great significance to human embryonic development mechanism and developmental biology, cell and tissue transplantation in the treatment of certain diseases. OBJECTIVE: To summarize the progress of in vitro culture of embryos and establishment of embryonic stem cell lines, to explore the influential factors for in vitro culture of embryos, and the methods of culturing human discarded embryos, isolating inner cell mass and establishing embryonic stem cell lines, as well as the establishing conditions for embryonic stem cell lines. METHODS: With the key words of “embryo, embryonic stem cells, coculture, sequential culture”, the first author searched CNKI and SCI databases for literatures concerning in vitro culture and transplantation of embryos and establishment of embryonic stem cell lines published from 2000 to 2014. Systematic evaluation was conducted. Finally, 58 literatures were retained for result analysis.  RESULTS AND CONCLUSION: The culturing condition for embryos in vitro is the key factor affecting embryo transfer outcomes, including culture medium component and culture system. In previous studies, the component and application of culture medium have changed greatly, and the culture system has altered from single culture to coculture and sequential culture. Ethical issues and embryonic origin restrictions restrict the establishment of human embryonic stem cell lines. Clinically discarded low-quality embryos can be used as one of the material sources to establish human embryonic stem cell lines, which can effectively lessen the problem of embryo shortage during the establishment of human embryonic stem cell lines and reduce ethical disputes. 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 全文链接： Figures and Tables | References | Related Articles | Metrics

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Hair follicle stem cells promote the healing of skin wound    Du Wei-bin, Quan Ren-fu, Zheng Xuan, Wang Tuo 2015, 19 (14):  2278-2282.  doi: 10.3969/j.issn.2095-4344.2015.14.025 Abstract ( 371 )   PDF (652KB) ( 600 )   Save BACKGROUND: Hair follicle stem cells derived from skin and hair have the most readily available sources, and cannot lead to serious complications and immunogenicity after collection, which can be used for autologous transplantation. OBJECTIVE: To provide effective experiment basis for hair follicle stem cells in the repair of skin wound through reviewing the role of hair follicle stem cells in promote the repair of skin wound. METHODS: Articles related to hair follicle stem cells for the repair of skin wound were retrieved in CNKI and PubMed databases (1999-01/2014-12). The key words were “hair follicle stem cell, skin repairing, regenerative medicine, tissue engineering” in Chinese and English, respectively. A total of 45 articles based on inclusion criteria and exclusion criteria were obtained for the review. RESULTS AND CONCLUSION: Hair follicle stem cells belong to adult stem cells, which are easy to access, have a significant number, and possess differentiation potential and safety. Hair follicle stem cells can promote the repair of skin wound and provides good seed cells for regenerative medicine and tissue engineering research through early vascularization of the skin, epidermal and appendage regeneration, signaling pathways, and transcription factors. 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 全文链接： Figures and Tables | References | Related Articles | Metrics

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Bone marrow microenvironment controls the “fate” of hematopoietic stem cells  Du Hua, Shi Ying-xu 2015, 19 (14):  2283-2290.  doi: 10.3969/j.issn.2095-4344.2015.14.026 Abstract ( 661 )   PDF (604KB) ( 793 )   Save BACKGROUND: Hematopoietic microenvironment regulates hematopoietic stem cells mainly through the cell-cell, cell-soluble regulator and cell-extracelluar matrix modes. OBJECTIVE: To review the molecular mechanism underlying regulation of hematopoietic stem cells under the cell-cell, cell-soluble factors and cell-extracellular matrix modes. METHODS: A computer-based online search of PubMed database was performed to search related articles with the key words of “Niche, HSC, VCAM-1, VLA-4, TPO, MPL, ECM, Integrin, N-cadherin, ANG-1, Tie2, VLA-5, Jagged-1, Notch, CXCL12, CXCR4, SCF, Kit, BMPs/TGF-β, TGF-βR, IFNα, IFNαR” in English. Irrelevant or repetitive studies as well as old literature were excluded, and finally 80 articles were included in result analysis. RESULTS AND CONCLUSION: Cells on the endosteal surface, vascular endothelial cells, perivascular cells, and some unknown or certain cells or small molecules in the bone marrow cavity constitute the specialized microenvironment for hematopoietic stem cells. Hematopoietic stem cells in the hematopoietic microenvironment remain a relatively steady state, which is the result of mutual contact of hematopoietic stem cells and hematopoietic microenvironment under the regulation of some important molecules, such as Pten and osteopontin, via the pathway between cell-intercellular adhesions, intercellular soluble factors, and cells and extracellular matrix. 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 全文链接： Figures and Tables | References | Related Articles | Metrics

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Spermatogonial stem cells and their biological characteristics: current situation, advances and applications Luo Yue-ji, Zeng Jie, Tang Rui-ling, Wang Xing-ming, Fan Li-qing 2015, 19 (14):  2291-2296.  doi: 10.3969/j.issn.2095-4344.2015.14.027 Abstract ( 301 )   PDF (682KB) ( 1105 )   Save BACKGROUND: Spermatogonial stem cells with abilities of differentiation, self renewal and proliferation are a kind of adult stem cells that can transfer genetic information into offspring, which have great application prospects in medicine, genetics and zoology. OBJECTIVE: To review the source, biological characteristics, and application of spermatogonial stem cells as well as self-renewal and molecular regulation underlining these differentiations. METHODS: PubMed and CNKI databases were searched by the first author using key words of “spermatogonial stem cell, biological characteristics, self-renewal, differentiation” in English and in Chinese, respectively, to retrieve relevant articles published from 1990 to 2015. Literatures addressing spermatogonial stem cells were included, and 46 articles were chosen for further analysis eventually. RESULTS AND CONCLUSION: Spermatogonial stem cells can be cultured in vitro, cryopreserved, and genetically modified as well as used for allogeneic or xenogeneic transplantation, all of which contribute to understanding the mechanisms of spermatogenesis, thereby providing new means for treatment of male sterile disease and genetic diseases and providing new hopes for chemotherapy-induced germ cell damage in young cancer patients. Microenvironment and Plzf, GDNF, SCF/c-Kit signaling pathways can play an important role in the regulation of spermatogonial stem cell self-renewal and differentiation. As a cell model, spermatogonial stem cells become an important tool for the researches on spermatogenesis mechanism, regeneration of spermatogenesis in sterile individuals and reproduction of transgenic animals. 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 全文链接： Figures and Tables | References | Related Articles | Metrics