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02 September 2016, Volume 20 Issue 36 Previous Issue    Next Issue

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Tumor necrosis factor alpha-induced apoptosis in bone marrow mesenchymal stem cells Li Jie-mei, Wang Huai-gao, Deng Da-shi, Lu Fang, Zhang Chen-chen, Liu Guo-zeng, Zhou Yan-fang 2016, 20 (36):  5325-5331.  doi: 10.3969/j.issn.2095-4344.2016.36.001 Abstract ( 200 )   PDF (1359KB) ( 269 )   Save BACKGROUND: Stem cell transplantation has achieved good results in the treatment of cerebral ischemia, and how to reduce apoptosis of transplanted cells has become the focus of the therapy. OBJECTIVE: To investigate the injured effect of tumor necrosis factor alpha (TNF-α) on bone marrow mesenchymal stem cells and its mechanism. METHODS: Primary cultured bone marrow mesenchymal stem cells from Sprague-Dawley rats were treated with 200 μg/L TNF-α for 6 hours. Cell vitality was assayed by MTT, and cell apoptosis was observed by Hoechst33342 staining. Apoptotic rate was detected by Annexin-V/PI double staining. Level of oxidative stress was evaluated by determination of malondialdehyde and superoxide dismutase levels. The protein expressions of phosphorylated-Akt, Akt, phosphorylated-FoxO1, FoxO1 were detected by western blot analysis. RESULTS AND CONCLUSION: After treatment with TNF-α, the cell vitality of bone marrow mesenchymal stem cells decreased, the apoptotic rate increased, and the cells were arrested in the S phase. Moreover, the oxidative stress level was elevated, and the protein expression of phosphorylated-Akt and phosphorylated-FoxO1 was significantly reduced compared with the control group (P < 0.05). These results suggest that TNF-α at high level contributes to the S-stage arrest, responsible for the apoptosis processes of bone marrow mesenchymal stem cells via the Akt-FoxO1 pathway.   中国组织工程研究杂志出版内容重点：干细胞；骨髓干细胞；造血干细胞；脂肪干细胞；肿瘤干细胞；胚胎干细胞；脐带脐血干细胞；干细胞诱导；干细胞分化；组织工程 Figures and Tables | References | Related Articles | Metrics

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MicroRNA-126 effects on free flap activity by regulating bone marrow mesenchymal stem cells Chen Yong, Fan Long-kun 2016, 20 (36):  5332-5337.  doi: 10.3969/j.issn.2095-4344.2016.36.002 Abstract ( 280 )   PDF (1180KB) ( 214 )   Save BACKGROUND: MicroRNA has tissue and cell specificity, and high expression of endothelial cell-specific microRNA-126 (miR-126) plays an important role in angiogenesis. OBJECTIVE: To explore the effect of miR-126 on transplanted free flap survival and histological activity as well as its mechanism in angiogenesis. METHODS: Transient transfection technology was used to enhance the expression of miR-126 in bone marrow mesenchymal stem cells. Expression levels of macrophage inflammatory protein-1α, tumor necrosis factor-α and vascular cell adhesion molecule-1 mRNA were detected by real-time PCR, and expression levels of ERK1/2, AKT, pERK1/2, pAKT protein were measured by western blot assay. Forty-eight Sprague-Dawley rats were randomly divided into three groups (n=16 per group), followed by preparation of abdominal free flap models. Rats in the three groups were given injection of miR-126 mimics-transfected cells, miR-126 mimics control-transfected cells and PBS 1 cm and 3 cm distal to the free flap, respectively. RESULTS AND CONCLUSION: Expression levels of macrophage inflammatory protein-1α, tumor necrosis factor-α and vascular cell adhesion molecule-1 mRNA in the cells transfected with miR-126 mimics were decreased by 36, 3.5 and 14 times compared with those in the PBS group, respectively. Expressions levels of ERK1/2, AKT, pERK1/2, pAKT protein in the distal free flap increased significantly in the miR-126 mimics group than the other two groups, as did the ratios of pAKT/AKT and pERK1/2/ERK1/2. In addition, the expression levels of macrophage inflammatory protein-1α, tumor necrosis factor-α and vascular cell adhesion molecule-1 protein in the flap tissue fluid were significantly lower in the miR-126 mimics transfection group than the other two group. All these findings suggest that miR-126 can promote free flap survival by creating favorable conditions for angiogenesis in the free flap tissue.   中国组织工程研究杂志出版内容重点：干细胞；骨髓干细胞；造血干细胞；脂肪干细胞；肿瘤干细胞；胚胎干细胞；脐带脐血干细胞；干细胞诱导；干细胞分化；组织工程 Figures and Tables | References | Related Articles | Metrics

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Construction of a lentivirus vector containing Pax6 and its transfection of human bone marrow mesenchymal stem cells Liu Jing-wen, Ren Jing, Chen Sheng, Li Bai-jun, Liu Shen-wen, Qin Bo 2016, 20 (36):  5338-5344.  doi: 10.3969/j.issn.2095-4344.2016.36.003 Abstract ( 357 )   PDF (2849KB) ( 269 )   Save BACKGROUND: Pax6 gene plays an important role in eye development and differentiation, and to study how it regulates the differentiation of human bone marrow mesenchymal stem cells (BMSCs), gaining the BMSCs stably over-expressing Pax6 is crucial, which is also the basis of stem cell replacement therapy. OBJECTIVE: To construct a lentivirus vector containing Pax6 and detect the expression of Pax6 in transfected human BMSCs. METHODS: Pax6 gene was extracted using PCR. After its connection with lentivirus vector pHIV-EGFP, it was then packaged by 293T cells. The human BMSCs were transfected with recombinant lentivirus Pax6-EGFP as well as lentivirus vector pHIV-EGFP, which was considered negative control group. The cellular morphology was observed by a fluorescence microscope, and the mRNA expression of Pax6 was detected by real-time PCR. RESULTS AND CONCLUSION: The recombinant lentivirus Pax6-EGFP was constructed successfully with a titer of 3×109 pfu/L. After the transfection, both the green fluorescent protein and Pax6 gene were expressed detected using fluorescence microscope and real-time PCR, showing that the method of lentiviral transfection is a safe and effective way to modify BMSCs.   中国组织工程研究杂志出版内容重点：干细胞；骨髓干细胞；造血干细胞；脂肪干细胞；肿瘤干细胞；胚胎干细胞；脐带脐血干细胞；干细胞诱导；干细胞分化；组织工程 Figures and Tables | References | Related Articles | Metrics

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Tumor-killing effects of gastric cancer stem cells as antigens to stimulate dendritic cells combined with cytokine-induced killer cells Wen Li-hong, Hu Wen-jie, Ye Heng-xi, Xiang Wei-dong 2016, 20 (36):  5345-5350.  doi: 10.3969/j.issn.2095-4344.2016.36.004 Abstract ( 393 )   PDF (3402KB) ( 228 )   Save BACKGROUND: As the existence of tumor stem cells, it is difficult to completely eliminate tumors in clinic. OBJECTIVE: To explore the tumor-killing effect of gastric cancer stem cells as antigen to stimulate dendritic cells combined with cytokine-induced killer cells. METHODS: Side population cells from human gastric cancer cell lines were isolated, and tumor antigen was prepared by freeze thawing method. After coculture with dendritic cells, dendritic cells combined with cytokine-induced killer cells, gastric cancer cell antigen, and gastric cancer stem cell antigen, killing rates of gastric cancer cells were detected using MTT assay. Expression rate of CD83, a mature dendritic cell surface marker, was also detected. RESULTS AND CONCLUSION: The CD83 expression level and killing rate of gastric cancer cells were both significantly lower in the gastric cancer stem cell antigen group than the other groups (both P < 0.05). These results indicate that gastric cancer stem cells as antigen to stimulate dendritic cells combined with cytokine-induced killer cells can promote the proliferation of gastric cancer cells and elevate the ability to killing gastric cancer 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 Figures and Tables | References | Related Articles | Metrics

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Combination effect of AMD3100 and dexamethasone on the mobilization of hematopoietic stem cells Yan Bei-zhan, Ma Hui-min, Kong Cun-quan, Liang Yu, Zhu Wei-yan, Jiang Shu-ting 2016, 20 (36):  5351-5357.  doi: 10.3969/j.issn.2095-4344.2016.36.005 Abstract ( 479 )   PDF (959KB) ( 246 )   Save BACKGROUND: The number of hematopoietic stem cells in the peripheral blood is very low at normal physiological state. So it is critical to mobilize hematopoietic stem cells from donor’s bone marrow into the peripheral blood. OBJECTIVE: To study the combination effect of AMD3100 and dexamethasone on the mobilization of hematopoietic stem cells in mice, thereby laying the foundation for clinical application. METHODS: C57BL/6 mice were injected with AMD3100 and dexamethasone alone or in combination. Then, hematopoietic stem cells in the peripheral blood and bone marrow were collected. CD34+ cell concentration in the peripheral blood and bone marrow was determined by flow cytometer and the content of leucocytes in the peripheral blood was counted by a normal method. The CFU-Mix colony formation ability of hematopoietic stem cells was identified by cell colony forming assay. RESULTS AND CONCLUSION: The concentration of CD34+ cells in the peripheral blood and bone marrow, the content of leukocytes in the peripheral blood and the CFU-Mix colony formation ability of hematopoietic stem cells were all improved by both AMD3100 and dexamethasone and especially their combined use. This indicates that both AMD3100 and dexamethasone could mobilize hematopoietic stem cells to migrate from the bone marrow to the peripheral blood, and when used in combination, the mobilization effect is better than that of single drug.   中国组织工程研究杂志出版内容重点：干细胞；骨髓干细胞；造血干细胞；脂肪干细胞；肿瘤干细胞；胚胎干细胞；脐带脐血干细胞；干细胞诱导；干细胞分化；组织工程 Figures and Tables | References | Related Articles | Metrics

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Effect of rat bone marrow mesenchymal stem cells on dynamic changes of inflammatory factors and apoptosis index during hepatocarcinogenesis Zhang Qing-qin, Kou Xiao-ge, Cui Yan-hui, Wang Luo-nan, Jin Cai-ling, Chen Mei-ling, Li Wei-wei 2016, 20 (36):  5358-5363.  doi: 10.3969/j.issn.2095-4344.2016.36.006 Abstract ( 215 )   PDF (979KB) ( 226 )   Save BACKGROUND: Bone marrow mesenchymal stem cell transplantation has not been thoroughly reported on its effects on apoptosis in hepatoma carcinoma cells and inflammatory factor level. OBJECTIVE: To investigate the effect of rat bone marrow mesenchymal stem cells on dynamic change of inflammatory factors and cell apoptosis during hepatocarcinogenesis. METHODS: Sixty healthy Sprague-Dawley rats were divided randomly into healthy group (n=30), control group (n=30) and transplantation group (n=30). Healthy group was given ordinary feed and normal water, while other groups were given diethylnitrosamine solution in drinking water to induce liver cancer models. Then, rats in the transplantation group were subjected to bone marrow mesenchymal stem cell transplantation via the tail vein. Two weeks after cell transplantation, CXCL5, interleukin-8 and interleukin-6 levels were tested by ELISA, mRNA level of hepatocyte nuclear factor 1α detected by RT-PCR, expression of Bcl-2 and Bax in liver tissue measured by immunohistochemical method, and liver cancer cell apoptosis index detected by TUNEL technique. RESULTS AND CONCLUSION: After modeling, the expressions of CXCL5, interleukin-8 and interleukin-6 in the control group were significantly higher than those in the healthy group (P < 0.05), while these indexes were reduced significantly after bone marrow mesenchymal stem cell transplantation (P < 0.05) and close to the normal levels (P > 0.05). Bone marrow mesenchymal stem cell transplantation significantly up-regulated the mRNA level of hepatocyte nuclear factor 1α in the liver tissue that was decreased obviously after modeling (P < 0.05). In addition, the expression of Bcl-2 was reduced, while the expression of Bax and the apoptosis index increased significantly in the transplantation group compared with the control group (P < 0.05). These findings indicate that bone marrow mesenchymal stem cell transplantation contributes to hepatocyte differentiation and regeneration in liver cancer rats by reducing serum inflammatory factor levels and promoting apoptosis in hepatoma carcinoma 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 Figures and Tables | References | Related Articles | Metrics

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Variation of blood biochemical indices in liver cirrhosis rats after adipose-derived mesenchymal stem cell transplantation Han Hai-yan, Song Wen-guang 2016, 20 (36):  5364-5370.  doi: 10.3969/j.issn.2095-4344.2016.36.007 Abstract ( 228 )   PDF (1270KB) ( 256 )   Save BACKGROUND: Stem cell transplantation is a promising treatment of advanced liver disease, and adipose-derived mesenchymal stem cells have become another kind of popular cells following bone marrow mesenchymal stem cells. OBJECTIVE: To investigate the influence of adipose-derived mesenchymal stem cell transplantation on blood biochemical indices of liver cirrhosis rats. METHODS: Sixty rats were equally randomized into normal control, model and cell transplantation groups. Model rats of liver cirrhosis were made in the latter two groups through intragastric administration of carbon tetrachloride. One week after successful modeling, rats were given intraperitoneal injection of adipose-derived mesenchymal stem cell suspension in the cell transplantation group, and given normal saline in the other two groups. RESULTS AND CONCLUSION: Compared with the normal control group, the model group showed a significant increase in the levels of alanine aminotransferase, aspartate aminotransferase, total bilirubin, total protein in liver tissues, serum level of malondialdehyde, 15-minute indocyanine green retention rate and degree of hepatic fibrosis, and a significant decrease in serum albumin level, serum albumin/globulin, levels of glutathione peroxidase and cyclic guanosine monophosphate in liver tissues. On the contrary, these indicators were all improved in the cell transplantation group compared with the model group. Moreover, CM-Dil-positive cells were visible in the liver tissue of rats undergoing adipose-derived mesenchymal stem cell transplantation. All these findings indicate that adipose-derived mesenchymal stem cell transplantation can reduce liver cirrhosis in rats by acting on blood biochemistry levels.   中国组织工程研究杂志出版内容重点：干细胞；骨髓干细胞；造血干细胞；脂肪干细胞；肿瘤干细胞；胚胎干细胞；脐带脐血干细胞；干细胞诱导；干细胞分化；组织工程 Figures and Tables | References | Related Articles | Metrics

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Bone marrow mesenchymal stem cell transplantation improves behavior performance of senile dementia rats Zhang Ying, Guo Jian-hua, Yan Hong-juan, Luo Qiu-hua, Li Xin-ping, Guo Wei, Wang Hai-xia 2016, 20 (36):  5371-5377.  doi: 10.3969/j.issn.2095-4344.2016.36.008 Abstract ( 339 )   PDF (4278KB) ( 222 )   Save BACKGROUND: More recently, studies have demonstrated that bone marrow mesenchymal stem cells can be induced in vitro to differentiate into neuron-like cells that are used for in vivo transplantation to repair nerve damage. OBJECTIVE: To study the effect of bone marrow mesenchymal stem cell transplantation on learning and memory ability of senile dementia rats. METHODS: Thirty male Sprague-Dawley rats were randomly divided into three groups: normal control group, stem cell therapy group and model control group. Rats in the latter two groups were used to establish animal models of senile dementia by intracranial injection of β-amyloid 1-40. Three weeks after modeling, rats were given bilateral hippocampal injection of induced bone marrow mesenchymal stem cell suspension in the stem cell therapy group, whereas no treatment was given in the normal control and model control groups. Morris water maze test was used to detect learning and memory ability of rats, and rat’s brain tissues were detected pathologically using hematoxylin-eosin staining. RESULTS AND CONCLUSION: After modeling, the escape latency was higher and the cross-platform frequency was lower in the model control group compared with the normal control group. After cell transplantation, the escape latency and cross-platform frequency were gradually shortened and increased with time, respectively. Compared with the model control group, the learning and memory abilities of rats were improved in the stem cell therapy group. The brain tissues were relatively intact in structure and exhibited less cell degeneration and necrosis in the stem cell therapy group compared with the model control group. To conclude, bone marrow mesenchymal stem cell transplantation exerts certain therapeutic effects on senile dementia by effectively improving the learning and memory ability.   中国组织工程研究杂志出版内容重点：干细胞；骨髓干细胞；造血干细胞；脂肪干细胞；肿瘤干细胞；胚胎干细胞；脐带脐血干细胞；干细胞诱导；干细胞分化；组织工程 Figures and Tables | References | Related Articles | Metrics

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Transplanting virus-transfected bone marrow stromal stem cells at different time against brain injury Liu Hong-lin, Liu Zhi-jun, Chen Xiao-bing, Hu Wen-zhong, Ding Bing-qian 2016, 20 (36):  5378-5384.  doi: 10.3969/j.issn.2095-4344.2016.36.009 Abstract ( 229 )   PDF (4652KB) ( 222 )   Save BACKGROUND: Bone marrow stromal cells can differentiate into nerve cells to promote nerve tissue repair, but the exact mechanism has not been fully elucidated. OBJECTIVE: To explore the influence of adenovirus-mediated β nerve growth factor transfection on bone marrow stromal stem cell transplantation fighting against brain injury in rats. METHODS: (1) Rat bone marrow stromal stem cells were cultured in vitro, transfected with the adenovirus-mediated β nerve growth factor and directionally induced using β-mercaptoethanol. (2) A total of 210 Sprague-Dawley rats were randomized into induction+tranfection group, induction+non-transfection group, induction+medium group, model group, and sham group (n=42 per group). Rat skull injury models were made, and given corresponding treatments at different time points (12, 24, 36, 48, 72 hours). Neurological function of rats was evaluated based on neurological severity scores on the day that the rats were given transplantation, and 1, 2, 3, 4 weeks after transplantation. (3) Another 75 Sprague-Dawley rats were also divided into five groups (n=15 per group) as above, followed by model establishment and corresponding treatments at 24 hours after modeling. Neurological severity scores were recorded at the same day, 1, 2, 3, 4 weeks after transplantation. Five rats from each group were sacrificed to detect levels of malondialdehyde and superoxide dismutase in the rat brain at the same day, 2 and 4 weeks after transplantation, respectively. RESULTS AND CONCLUSION: If the cells were transplanted within 48 hours after modeling, the neurological severity scores in the induction+transfection group decreased significantly compared with the induction+non-transfection group and model group at 1 and 2 weeks after transplantation (P < 0.05). If the cells were transplanted at different time, the neurological severity scores in the induction+transfection group were decreased significantly compared with the induction+non-transfection group and model group at 3 and 4 weeks after transplantation (P < 0.05). If the cells were transplanted within 24 hours after modeling, the neurological severity scores in the induction+transfection group decreased significantly compared with the model group at 1 week after transplantation (P < 0.05), and the neurological severity scores in the induction+transfection group and induction+non-transfection group both were significantly lower than those in the model group (P < 0.05). Two weeks after cell transplantation, the level of superoxide dismutase was significantly higher in the induction+transfection group than the induction+medium group and model group (P < 0.05), but the level of malondialdehyde was significantly lower (P < 0.05). All these findings indicate that adenovirus-mediated β nerve growth factor transfer plays a certain neuroprotective role in bone marrow stromal stem cell transplantation for brain 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 Figures and Tables | References | Related Articles | Metrics

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Effect of basic fibroblast growth factor gene transfection on bone marrow mesenchymal stem cell transplantation for diabetes mellitus Tian Xue-pin, Liu Hai-ying 2016, 20 (36):  5385-5391.  doi: 10.3969/j.issn.2095-4344.2016.36.010 Abstract ( 439 )   PDF (4563KB) ( 169 )   Save BACKGROUND: Existing studies have shown that bone marrow mesenchymal stem cells can significantly improve islet function in diabetic rats to decrease excessively high blood glucose level, which may be related to the enhancement of differentiation ability of autologou pancreatic stem cells. OBJECTIVE: To observe the therapeutic efficacy of basic fibroblast growth factor gene eukaryotic expression vector (PEGFP-C3-BFGF) transfection of bone marrow mesenchymal stem cells in diabetic rats. METHODS: Recombinant adenovirus (Ad.aFGF) mediated PEGFP-C3-BFGF was transfected into bone marrow mesenchymal stem cells, and PEGFP-C3-BFGF expression was observed using fluorescence microscopy. Eighty Sprague-Dawley rats were randomly divided into normal control group, diabetes group, transplantation group, gene transfection group, with 20 rats in each group. After modeling, rats in different groups were given portal vein injection of normal saline, PBS, 1 mL of bone marrow mesenchymal stem cell suspension, and 1 mL of PEGFP-C3-BFGF-transfected bone marrow mesenchymal stem cell suspension. RT-PCR method was used to detect mRNA expression of matrix metalloproteinases in pancreatic tissue of rats in each group. Blood glucose levels of rats were detected at 24 hours, 3, 7, 14, 21 days after transplantation. ELISA method was used to detect plasma insulin levels in rats. Pathological changes of the pancreas were observed using hematoxylin-eosin staining. RESULTS AND CONCLUSION: Under the fluorescence microscope, PEGFP-C3-BFGF transfected into cells after 48 hours showed significant specific red fluorescence. Two weeks after transplantation, matrix metalloproteinases mRNA expression was significantly increased in the diabetes group compared with the control group (P < 0.05), while it was decreased in the transplantation and gene transfection groups compared with the diabetes group (P < 0.05). After transplantation, the blood glucose levels in rats were ranked as follows: control group < gene transfection group < transplantation group < diabetes group (P < 0.05), and the plasma insulin levels in rats ranked as follows: control group > gene transfection group > transplantation group > diabetes group (P < 0.05). Pathological findings of the pancreas showed that the transplantation group was superior to the diabetes group, but inferior to the gene transfection group that was similar to the control group. All these findings indicate that PEGFP-C3-BFGF-transfected bone marrow mesenchymal stem cell transplantation can improve blood glucose levels and stimulate insulin secretion in diabetic rats, which may improve the severity of diabetes mellitus by decreasing the mRNA expression of matrix metalloproteinases.   中国组织工程研究杂志出版内容重点：干细胞；骨髓干细胞；造血干细胞；脂肪干细胞；肿瘤干细胞；胚胎干细胞；脐带脐血干细胞；干细胞诱导；干细胞分化；组织工程 Figures and Tables | References | Related Articles | Metrics

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Autologous bone marrow stem cell transplantation for liver cirrhosis via the hepatic artery in rabbits Wang Hai-fang, Liu Hong-xia, Shao Fei, Jia Bei, Zhang Sui, Zhou Jing 2016, 20 (36):  5392-5397.  doi: 10.3969/j.issn.2095-4344.2016.36.011 Abstract ( 251 )   PDF (3959KB) ( 215 )   Save BACKGROUND: How to make more transplanted bone marrow stem cells stay and differentiate in the liver is an important issue, which is also crucial for treatment of liver cirrhosis via the hepatic artery. OBJECTIVE: To investigate the therapeutic effect of autologous bone marrow stem cell transplantation via the hepatic artery on liver cirrhosis. METHODS: Thirty New Zealand white rabbits were equivalently randomized into normal control, stem cell transplantation and model groups. Animal models of liver cirrhosis were made in the latter two groups. Then, model rabbits in the stem cell transplantation group were subjected to autologous bone marrow stem cell transplantation via the hepatic artery. Liver function of rabbits was detected in 1, 2, 4, 8, 10 weeks after cell transplantation, and pathological detection of the liver was performed in the 10th week. RESULTS AND CONCLUSION: At 10 weeks after cell transplantation, the liver function of the rabbits was improved significantly compared with the model group, including reduced activities of serum alanine aminotransferase, total bilirubin and aspartate aminotransferase, shortened activated partial thromboplastin time, and increased albumin level (P < 0.05). Pathological examination of the liver showed that the liver cells in the stem cell transplantation group were intact with no obvious edema and still had the structure of the pseudolobule, and compared with the model group, the degree of liver fibrosis was significantly reduced in the stem cell transplantation group. Our experimental results show that the transplantation of autologous bone marrow stem cells via the hepatic artery has a certain therapeutic effect on liver cirrhosis by increasing the body albumin content in a short time and improving the liver function.   中国组织工程研究杂志出版内容重点：干细胞；骨髓干细胞；造血干细胞；脂肪干细胞；肿瘤干细胞；胚胎干细胞；脐带脐血干细胞；干细胞诱导；干细胞分化；组织工程 Figures and Tables | References | Related Articles | Metrics

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Human umbilical cord blood mononuclear cell transplantation for treatment of radioactive premature ovarian failure in nude mice Wang Yi-feng, Song Wen-guang, Liu Shu-xia 2016, 20 (36):  5398-5404.  doi: 10.3969/j.issn.2095-4344.2016.36.012 Abstract ( 309 )   PDF (5198KB) ( 254 )   Save BACKGROUND: Stem cell transplantation, in recent years, has become a preferred treatment for premature ovarian failure. Umbilical cord blood mononuclear cells containing a large number of mesenchymal stem cells, immature stem/progenitor cells, and endothelial progenitor cells can be used as an important source of stem cell transplantation. OBJECTIVE: To study the therapeutic efficacy of human umbilical cord blood mononuclear cell transplantation on radioactive premature ovarian failure in nude mice. METHODS: 120 female BALB/C nude mice were randomly divided into four groups: blank control group without any intervention; model group, intravenous transplantation group, and in situ transplantation group exposed to 60Co γ rays, 0.5 Gry per day, for 30 days. After 30 days, premature ovarian failure models were made in the latter three groups. Then, nude mice in the latter three groups were given bilateral ovary injection of 10 µL DMEM, tail vein injection of 10 µL human umbilical cord blood mononuclear cells (1×1013/L), and bilateral ovary injection of 10 µL human umbilical cord blood mononuclear cells (1×1013/L), respectively. Thirty days after cell transplantation, serum levels of estradiol, follicle hormone, luteinizing hormone, inhibin B and vascular endothelial growth factor were detected, cell apoptosis in the ovary tissue and cell survival were observed pathologically. RESULTS AND CONCLUSION: After modeling, the serum levels of estradiol, inhibin B and vascular endothelial growth factor were significantly reduced (P < 0.01), while follicle hormone and luteinizing hormone levels increased (P < 0.01). After transplantation, these indexes were all improved in the in situ transplantation group (P < 0.01), and reduced follicle hormone and luteinizing hormone levels were visible in the intravenous transplantation group (P< 0.05,P < 0.01). Compared with the model group, in situ transplantation and intravenous injection of human umbilical cord blood mononuclear cells could effectively reduce cell apoptosis in the ovary tissue (P < 0.05), and transplanted cells were able to survive in the ovary of nude mice. All these findings show human umbilical cord blood mononuclear cell transplantation do have curative effects on premature ovarian failure in nude mice through the inhibition of apoptosis and the regulation of hormone secretion.   中国组织工程研究杂志出版内容重点：干细胞；骨髓干细胞；造血干细胞；脂肪干细胞；肿瘤干细胞；胚胎干细胞；脐带脐血干细胞；干细胞诱导；干细胞分化；组织工程 Figures and Tables | References | Related Articles | Metrics

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Protective mechanism of cardiac stem cells against myocardial apoptosis Gao Xue-dong, Hu Ke, Wei Hu 2016, 20 (36):  5405-5411.  doi: 10.3969/j.issn.2095-4344.2016.36.013 Abstract ( 306 )   PDF (4150KB) ( 667 )   Save BACKGROUND: Myocardial apoptosis can lead to many kinds of heart diseases, but most of the conventional treatments cannot get desired effects. The emergence of cardiac stem cell related theory that subverts the previous view of myocardial cells provides a new idea for the treatment of a variety of heart diseases. OBJECTIVE: To investigate the protective mechanism of cardiac stem cells in myocardial apoptosis. METHODS: Cardiac stem cells were isolated from five neonatal rats. Another 20 Wistar rats were selected to make myocardial infarction models, and then model rats were equivalently randomized into observation and control groups. One day after modeling, rats in each group were given injection of cardiac stem cells or culture solution. Fourteen days after injection, myocardial apoptosis index was calculated and expression of apoptosis-related proteins was detected in both groups. RESULTS AND CONCLUSION: After continuous 3 days of culture, a completely spread growth in the cardiac tissues was visible, and a small amount of cells similar to fibrocytes climbed out from the cardiac tissue sample. These cells isolated using magnetic bead method were sub-cultured for 5 days, and found to be regrouped again. Compared with the control group, the apoptotic index, Fas and Fasl expression were significantly lower (P < 0.05), and Bcl-2 expression was significantly higher in the observation group (P < 0.05). All these findings show that cardiac stem cell transplantation can effectively regulate the expression of apoptosis-related proteins and inhibit the apoptosis of myocardial cells in rats with myocardial infarction.   中国组织工程研究杂志出版内容重点：干细胞；骨髓干细胞；造血干细胞；脂肪干细胞；肿瘤干细胞；胚胎干细胞；脐带脐血干细胞；干细胞诱导；干细胞分化；组织工程 Figures and Tables | References | Related Articles | Metrics

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CARM1 is required to maintain stemness of amniotic fluid-derived stem cells Wu Jing, Zhao Li-hua 2016, 20 (36):  5412-5418.  doi: 10.3969/j.issn.2095-4344.2016.36.014 Abstract ( 308 )   PDF (3252KB) ( 201 )   Save BACKGROUND: Studies have shown that methylation modification using CARM1-catalyzed histone H3R17/R26 can maintain the stemness of embryonic stem cells. However, mechanism underlying CARM1 effect on the stemness of amniotic fluid-derived stem cells is still unclear. OBJECTIVE: To investigate the function and underlying molecular mechanism of CARM1 to maintain stemness in the amniotic fluid-derived stem cells. METHODS: Amniotic fluid-derived stem cells from term pregnancy were isolated and cultured. RT-PCR was used to identify the stem cell mark and CARM1 gene expression. CARM1 expression in amniotic fluid-derived stem cells was knocked down by using two shRNA. RT-qPCR was used to detect the silencing efficiency, and western blot employed to examine the methylation level of Arginines 17 at N terminus of histone 3 (H3mR17). Moreover, the expression of embryonic stem cell markers, including OCT4, SOX2 and NANOG, were detected. RESULTS AND CONCLUSION: Amniotic fluid-derived stem cells from term pregnancy could express CARM1 and stem cell markers, including OCT4, SOX2, Nanog and KLF4. Both of the shRNAs could knock down the expression of CARM1 efficiently. When CARM1 was knocked down, the H3mR17 level was decreased and OCT4, SOX2 expression was also reduced, but NANOG expression had no change. All these indicate that CARM1 is required for amniotic fluid-derived stem cells to maintain stemness through regulating OCT4 and SOX2 expression.   中国组织工程研究杂志出版内容重点：干细胞；骨髓干细胞；造血干细胞；脂肪干细胞；肿瘤干细胞；胚胎干细胞；脐带脐血干细胞；干细胞诱导；干细胞分化；组织工程 Figures and Tables | References | Related Articles | Metrics

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Methylprednisolone effects on the migration of endogenous neural stem cells after spinal cord injury Qu Yi-ming, Li Bo, Wang Qun-bo, Shao Gao-hai, Lu Min-peng, Yu Yu, Liu Zuo-zhong, Cao Chun-feng 2016, 20 (36):  5419-5425.  doi: 10.3969/j.issn.2095-4344.2016.36.015 Abstract ( 276 )   PDF (1263KB) ( 273 )   Save BACKGROUND: After spinal cord injury, endogenous neural stem cells are activated to proliferate and migrate to repair damaged tissue. As a clinical medicine, methylprednisolone shows a lot of functions, but its effects on endogenous neural stem cells are still unknown. OBJECTIVE: To explore the effects of methylprednisolone on the proliferation and migration of endogenous neural stem cells after spinal cord injury. METHODS: Seventy-five Sprague-Dawley rats were used to make animal models of T10 complete paraplegia using Allen’s method, and randomized into methylprednisolone, normal saline and model groups. Rats in these three groups were given intraperitoneal injection of 1 g/L methylprednisolone solution at a dose of 30 mg/kg for 10 minutes and at a dose of 5.4 mg/kg/h for 23 hours, given intraperitoneal injection of normal saline at the same dose and given no treatment, respectively. Neurological and motor functions were assessed by somatosensory evoked potential and Basso Beattie Bresnahan scores at 7, 14, 21, 28 days after spinal cord injury. BrdU and Nestin staining of the injured spinal cord segment was conducted. RESULTS AND CONCLUSION: A large amount of BrdU- and Nestin-positive cells were visible in all the groups, and the number of these cells reached the peach at 14 days after spinal cord injury. Methylprednisolone was found to inhibit BrdU-, Nestin- or double-positive cells, indicating methylprednisolone can inhibit the proliferation and migration of endogenous neural stem cells. The results of Basso Beattie Bresnahan scores showed no notable improvement in the motor function of the limbs. Methylprednisolone also showed no significant effects on the motor evoked potential latency, but promoted nerve conduction recovery. All these findings indicate that methylprednisolone has some hindering effects on spinal cord repair by inhibiting the proliferation and migration of endogenous neural stem cells after spinal cord injury.   中国组织工程研究杂志出版内容重点：干细胞；骨髓干细胞；造血干细胞；脂肪干细胞；肿瘤干细胞；胚胎干细胞；脐带脐血干细胞；干细胞诱导；干细胞分化；组织工程 Figures and Tables | References | Related Articles | Metrics

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Comparative analysis of the proliferation and differentiation of neural stem cells in the hippocampal dentate gyrus of rats with different ages Xie Qiang, Wang Fei, Zhou Guo-ping, Zhang Hui, Ma Jin-xian 2016, 20 (36):  5426-5431.  doi: 10.3969/j.issn.2095-4344.2016.36.016 Abstract ( 309 )   PDF (936KB) ( 238 )   Save BACKGROUND: Cerebral hemorrhage can activate the proliferation and differentiation of neural stem cells in the dentate gyrus of the hippocampus. Through continuous differentiation and proliferation, endogenous neural stem cells can gradually replace aging and damaged neurons, thus protecting the brain structure. OBJECTIVE: To compare the difference of the proliferation and differentiation of neural stem cells in the dentate gyrus of the hippocampus of rats with different ages. METHODS: Ninety-six adult rats and 96 aged rats were randomly divided into normal group (n=18 per group), sham operation group (n=12 per group) and cerebral hemorrhage group (model group, n=66 per group), respectively. Cerebral hemorrhage models were made in the two model groups in which, the rats were subjected to cerebral hemorrhage for 6, 24, 48, 72 hours and 7 days, respectively. Then, brain tissues were collected to measure brain water content. BrdU/NeuN and BrdU/GFAP double staining were performed at 3, 7, 14, 21, 28 days after surgery to calculate the number of positive cells. RESULTS AND CONCLUSION: For both adult and aged rats, the brain water content was significantly higher than that in the normal group and sham operation group (P < 0.05), while in the normal and sham operation groups, the brain water content was significantly lower in the aged rats than the adult rats (P  < 0.05). The number of bilateral BrdU-positive cells in the adult and aged model groups was significantly higher than that in the corresponding normal and sham operation groups (P  < 0.05), and moreover, the positive cell number at the hemorrhage side was significantly higher than that at the opposite side (P < 0.05). In addition, the number of BrdU-positive cells at the hemorrhage side in the adult rats was significantly higher than that in the aged rats at different time after cerebral hemorrhage (P  < 0.05). Results from immunohistochemical double staining showed that the BrdU/NeuN and BrdU/GFAP expression in the hippocampal dentate gyrus of adult rats with cerebral hemorrhage was significantly higher than that of normal adult rats. All these experimental results show that there are a few neural stem cells proliferating in the hippocampal dentate gyrus of normal rats, and the proliferation ability is stronger in the adult rats than the aged rats. Cerebral hemorrhage can significantly strengthen the proliferation of neural stem cells in the dentate gyrus in the adult rats compared with the aged 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 Figures and Tables | References | Related Articles | Metrics

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Mesenchymal stem cell transplantation for post-transplant renal function: a Meta-analysis Chen Cheng, Gu Yu-wei, Zhang Jun, Hu Lin-kun, Wei Xue-dong, Hou Jian-quan 2016, 20 (36):  5432-5439.  doi: 10.3969/j.issn.2095-4344.2016.36.017 Abstract ( 354 )   PDF (1352KB) ( 225 )   Save BACKGROUND: In recent years, with the use of new immunosuppressive agents, the survival rate of renal graft is greatly improved, but accompanied by lots of side effects and unchanged long-term graft survival. Mesenchymal stem cells (MSCs) have aroused people’s great interest, while their efficacy in kidney transplantation remains controversial. OBJECTIVE: To evaluate the efficacy of MSCs transplantation on post-transplant renal graft function with a systematic review. METHODS: PubMed, EMBASE, the Cochrane Library database, the Cochrane Central Register of Controlled Trials, Wanfang database and China National Knowledge Infrastructure (CNKI) were searched until November 2015. Revman 5.3 was used for statistical analysis. RESULTS AND CONCLUSION: A total of 6 randomized controlled trials were included, including 1 166 patients. Meta-analysis results showed that at 1, 2 weeks and 1 month after kidney transplantation, the posttransplantation estimated glomerular filtration rates in the MSC-treated group were significantly higher than those in the control group (P < 0.05). At 1, 3, 6, 12 months after kidney transplantation, the posttransplantation serum creatinine levels showed no significant difference between the MSC-treated group and the control group (P > 0.05). To conclude, MSC-based immunosuppression regimen is superior to current standard immunotherapy in improving renal graft function in the early stage after kidney transplantation, but the clinical efficacy is diminished in the later period. Therefore, further investigation using large-scale randomized controlled trials is warranted.   中国组织工程研究杂志出版内容重点：干细胞；骨髓干细胞；造血干细胞；脂肪干细胞；肿瘤干细胞；胚胎干细胞；脐带脐血干细胞；干细胞诱导；干细胞分化；组织工程 Figures and Tables | References | Related Articles | Metrics

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Induced pluripotent stem cells and cardiovascular disease Zhan Qi, Zhang Jing, Wang Xiao-qing, Chen Xiao-fang, Huang Yan 2016, 20 (36):  5440-5449.  doi: 10.3969/j.issn.2095-4344.2016.36.018 Abstract ( 297 )   PDF (1152KB) ( 269 )   Save BACKGROUND: Induced pluripotent stem cells have great prospects in tissue repair, due to the characteristic of self-renewal, multi-directional differentiation, no immunological rejection and ethics controversy. OBJECTIVE: To summarize the differentiation of induced pluripotent stem cells towards cardiomyocytes and endothelial cells, and their applications in the cardiovascular diseases. METHODS: The first author performed a data retrieval of PubMed and CNKI databases from 2000 to 2015 to search articles addressing the differentiation of induced pluripotent stem cells towards cardiomyocytes and endothelial cells, and reviewed the literatures systematically. Finally, 78 articles were chosen for further analysis. RESULTS AND CONCLUSION: Induced pluripotent stem cells can differentiate into cardiovascular cells through a variety of methods. Factors such as cyclosporin A and ascorbic acid C may improve myocardial differentiation of induced pluripotent stem cells, while vascular endothelial growth factor and basic fibroblast growth factor may improve the endothelial differentiation of induced pluripotent stem cells. Cardiovascular cells derived from induced pluripotent stem cells can be applied to build disease models in vitro, transplantation in vivo and drug screening.   中国组织工程研究杂志出版内容重点：干细胞；骨髓干细胞；造血干细胞；脂肪干细胞；肿瘤干细胞；胚胎干细胞；脐带脐血干细胞；干细胞诱导；干细胞分化；组织工程 Figures and Tables | References | Related Articles | Metrics

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Sirtuins in stem cell regulation: roles and prospects Mao Zhong-fu, Li Yi-fang, Hiroshi Kurihara, He Rong-rong 2016, 20 (36):  5450-5457.  doi: 10.3969/j.issn.2095-4344.2016.36.019 Abstract ( 668 )   PDF (1212KB) ( 263 )   Save BACKGROUND: Efficacy of stem cell therapy is considerably influenced by oxidative stress. Sirtuin (SIRT) family of mammals is an important deacetylation and antioxidant enzyme that can regulate endogenous antioxidant activities in stem cells and cell cycle related signaling pathways to reduce the damage and enhance the viability of stem cells. OBJECTIVE: To review the regulating function and mechanism of SIRT family. METHODS: A computer-based search of Web of Science, PubMed and CNKI from 1990 to 2015 was performed for relevant articles about SIRT and stem cell oxidative stress, using the key words of “SIRT, stem cell, oxidative stress, molecular mechanisms” in English and Chinese, respectively. After eliminating literatures which have poor authority or have similar contents, 55 articles were involved. RESULTS AND CONCLUSION: NAD+-dependent SIRT family is the key enzyme for deacetylation of histones and other proteins. It plays vital regulation roles in metabolism, genomic stability, DNA damage/repair, and chromatin remodeling/stress reaction. Progress in the SIRT-targeted stem cell research will definitely provide more clues for clinical stem cell transplantation therapy.   中国组织工程研究杂志出版内容重点：干细胞；骨髓干细胞；造血干细胞；脂肪干细胞；肿瘤干细胞；胚胎干细胞；脐带脐血干细胞；干细胞诱导；干细胞分化；组织工程 Figures and Tables | References | Related Articles | Metrics

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Application of human induced pluripotent stem cells-derived dopaminergic neurons in the Parkinson’s disease models: present and future Peng Ya-nan, Zhao Zhen-qiang 2016, 20 (36):  5458-5465.  doi: 10.3969/j.issn.2095-4344.2016.36.020 Abstract ( 322 )   PDF (1006KB) ( 209 )   Save BACKGROUND: The emergence of human induced pluripotent stem cells (iPSCs)-derived dopaminergic neurons solves the problem that the embryonic stem cell (ESC) shows an ethical issue on its source, providing a promising cell source for treatment of Parkinson’s disease. OBJECTIVE: To summarize the differentiation methods of iPSCs-derived dopaminergic neurons in vitro, the choice of Parkinson’s disease models and the transplantation of iPSCs-derived dopaminergic neurons in the Parkinson’s disease treatment. METHODS: In order to search relevant articles about the application of iPSCs-derived dopaminergic neurons in the Parkinson’s disease models from PubMed databases (from 1980 to 2015), a computer-based search was performed by the first author, using the key words of “iPSC and Parkinson’s disease, induced pluripotent stem cells and Parkinson’s disease, ES cells and Parkinson, PD model, Parkinson and Lewy bodies” in English. Finally 40 articles were chosen for further analysis. RESULTS AND CONCLUSION: Here, this paper is detailed to show the research status of human iPSCs-derived dopaminergic neurons for treating Parkinson’s disease by reviewing the sources and in vitro differentiation schedules of iPSCs as well as the choice of Parkinson’s disease models and outcomes of transplantation of iPSCs-derived dopaminergic neurons for Parkinson’s disease treatment. According to the Parkinson’s disease mechanism of the Lewy body, we analyze the generation mechanism of the Lewy body, providing references to avert the presence of Lewy bodies and optimize the outcomes of transplantation. The improvement of differentiation conditions of iPSCs can markedly improve the behavior outcomes, and moreover, we can systematically evaluate the outcomes of transplantation by iconography and immunohistochemical results.   中国组织工程研究杂志出版内容重点：干细胞；骨髓干细胞；造血干细胞；脂肪干细胞；肿瘤干细胞；胚胎干细胞；脐带脐血干细胞；干细胞诱导；干细胞分化；组织工程 Figures and Tables | References | Related Articles | Metrics

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Mesenchymal stem cells isolated from different sources differentiate into vascular endothelial cells under induction Wang Jun-li, Xu Hui-fang, Feng Li, Wei Dan, Chen Guo-hua 2016, 20 (36):  5466-5472.  doi: 10.3969/j.issn.2095-4344.2016.36.021 Abstract ( 389 )   PDF (967KB) ( 223 )   Save BACKGROUND: Mesenchymal stem cells (MSCs) can be differentiated into vascular endothelial cells to construct ideal blood vessel grafts in vitro that have wide prospective utility in the clinical treatment of ischemic diseases, vascular engineering and regeneration medicine. OBJECTIVE: To review the recent research progress and related issue in biological characteristics of MSCs as well as differentiation of MSCs isolated from different sources into vascular endothelial cells. METHODS: The first authors retrieved PubMed, Sciencedirect and Medline databases for relevant articles published from January 2000 to June 2015. The key words were “mesenchymal stem cells; vascular endothelial cell; cell differentiation” in English. Initially, 156 articles were retrieved, and finally 51 articles were included in result analysis. RESULTS AND CONCLUSION: The MSCs sources are abundant. The research about bone marrow-derived MSCs is the earliest and maximum, but with the increasing donor age, their proliferation and differentiation ability decreases. MSCs from umbilical cord, placenta and amniotic membrane are easy to obtain, and meanwhile both neonatal and maternal does not feel any pain and psychological burden. Given these, these cells are more acceptable for recipients, and there are no ethical, moral and legal disputes. MSCs from the umbilical cord blood are abundant with weak cell immunogenicity and low viral and bacterial contamination probability. However, the clinical application of amniotic fluid marrow-derived MSCs is limited because of its sampling methods.   中国组织工程研究杂志出版内容重点：干细胞；骨髓干细胞；造血干细胞；脂肪干细胞；肿瘤干细胞；胚胎干细胞；脐带脐血干细胞；干细胞诱导；干细胞分化；组织工程 Figures and Tables | References | Related Articles | Metrics