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28 March 2019, Volume 23 Issue 9 Previous Issue    Next Issue

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Differentiation of bone marrow mesenchymal stem cells into nucleus pulposusk-like cells induced by Nampt/NAD/Sirt1 axis of Achyranthes bidentata Bl. saponins Yue Zongjin, Liu Ruyin, Yu Lu, Peng Xiaoyan, Lu Hua 2019, 23 (9):  1313-1318.  doi: 10.3969/j.issn.2095-4344.1621 Abstract ( 424 )   PDF (703KB) ( 146 )   Save BACKGROUND: Studies have shown that bone marrow mesenchymal stem cells (BMSCs) can differentiate into nucleus pulposus-like cells, but the mechanism of differentiation is not clear. OBJECTIVE: To induce bone BMSCs into nucleus pulposus-like cells using Achyranthes bidentata Bl. saponins (ABS) and to explore the role of Nampt/NAD/Sirt1 axis in the differentiation of BMSCs. METHODS: BMSCs were collected from Sprague-Dawley rats. Cells at passage 3 were divided into four groups: BMSCs group, BMSCs+ABS group, BMSCs+ABS+nicotinamide mononucleotide (an exogenous small molecule substance promoting NAD synthesis) group, BMSCs+ABS+FK866 (nicotinamide phosphoribosyltransferase inhibitor) group, in which the cells were induced for 14 days. Alcian blue staining was used to show the changes of glycosaminoglycan in the cells. RT-PCR was used to detect the mRNA expression of COL2, Aggrecan, KRT19, Pax1. The protein expression level of COL2 was detected by western blot. The activity of Sirt1 was detected by Sirt1 assay kit and the content of NAD+ was measured by NAD+/NADH kit. RESULTS AND CONCLUSION: (1) Compared with the BMSCs group, BMSCs+ABS group showed significant increases in the expression levels of glycosaminoglycan, Aggrecan, KRT19, and Pax1 (P < 0.05), and the protein expression levels of COL2, activity of Sirt1, and content of NAD+ were also significantly increased (all P < 0.05). (2) Compared with the BMSCs+ABS group, the above-mentioned indicators were significantly increased in the BMSCs+ABS+nicotinamide mononucleotide (P < 0.05); on the contrary, these indicators were all decreased significantly in the BMSCs+ABS+FK866 group (P < 0.05). To conclude, ABS could induce the differentiation of rat BMSCs into nucleus pulposus-like cells, in which the Nampt/NAD/Sirt1 axis might play a promotion role. 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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Effects of CXCL12 and CXCR4 on chemotaxis of bone marrow stem cells towards endometrial stromal cells Huang Xiaoping, Zhang Juan, Wang Wenping, Fan Bo 2019, 23 (9):  1319-1323.  doi: 10.3969/j.issn.2095-4344.1642 Abstract ( 417 )   PDF (587KB) ( 114 )   Save BACKGROUND: Bone marrow stem cells can be colonized into the mouse endometrium. However, the molecular mechanisms underlying the migration of bone marrow stem cells into the endometrium are still unclear. OBJECTIVE: To investigate the effects of CXCL12 and CXCR4 on the chemotaxis of bone marrow stem cells towards endometrial stromal cells. METHODS: Mouse bone marrow stem cells and human endometrial stromal cells were serum-starved overnight. After 24 hours of estradiol pretreatment, the mRNA expressions of CXCR4 and CXCL12 in the mouse bone marrow stem cells were detected by RT-PCR; the levels of CXCL12 in the mouse bone marrow stem cells and human endometrial stromal cells were detected by ELISA; and the migration of mouse bone marrow stem cells into human endometrial stromal cells was observed by Transwell chamber test. RESULTS AND CONCLUSION: Estradiol pretreatment could upregulate the expression of CXCL12 in the human endometrial stromal cells as well as the expression of CXCR4 in the mouse bone marrow cells, promoting the migration of mouse bone marrow stem cells towards the conditioned medium of human endometrial stromal cells. In conclusion, estradiol can promote the migration of bone marrow stem cells into the endometrium, which may provide new ideas for the treatment of endometrial diseases. 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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Inflammation activated bone marrow mesenchymal stem cell conditioned medium repairs radiation-induced acute injury to intestinal epithelial stem cells Ma Faxin, Sha Weihong, Wang Qiyi, Li Jinliang, Lu Quan, Luo Yujun 2019, 23 (9):  1324-1329.  doi: 10.3969/j.issn.2095-4344.1602 Abstract ( 475 )   PDF (802KB) ( 375 )   Save BACKGROUND: Our previous findings indicate that inflammation-activated bone marrow mesenchymal stem cell conditioned medium (MSC-CM) contribute to repairing the structure and function of the small intestine after radiation-induced acute intestinal injury. However, it is unclear whether the repair effect can be achieved by regulating small intestinal stem cells. OBJECTIVE: To investigate the effects of inflammation-activated bone marrow MSC-CM on the small intestinal epithelial stem cells after acute radiation-induced intestinal injury and to further discuss the repairing mechanism. METHODS: Bone marrow mesenchymal stem cells of Sprague-Dawley rats were separated, cultured and identified. Then, the bone marrow mesenchymal stem cells were co-cultured with normal or radiation-induced IEC-6 cell lines in the Transwell system for 24 hours. Inflammation-activated bone marrow mesenchymal stem cells were cultured alone for 48 hours. Non-activated MSC-CM (MSC-CMNOR) and MSC-CM under radiation-induced inflammatory condition (MSC-CMIR) were collected. Adult Sprague-Dawley rats (provided by the Experimental Center of Sun Yat-Sen University North Campus) were randomly divided into four groups with 20 rats in each group: control group, radiation group, radiation+MSC-CMNOR group and radiation+MSC-CMIR group. The rats in the latter three groups were exposed to one-off 14 Gy whole abdominal radiation to make a rat model of acute radiation-induced small intestinal injury. Three-day continuous administration beginning within 4 hours after successful modeling was given via the tail vein and intraperitoneal implantation of Alzet micro-osmotic pumps: EMEM-F12 (200 μL/d) for the radiation group, MSC-CMNOR for radiation+MSC-CMNOR group and MSC-CMIR for radiation+MSC-CMIR group. There was 2 mL of concentrated conditioned medium in the pump which was released at a constant rate of 10 μL/h into the abdominal cavity after implantation. Intestinal samples were collected at 1, 3, 5, 7 days after radiation for immunochemistry staining, western blot and qRT-PCR detection. RESULTS AND CONCLUSION: (1) On the 3rd day after radiation, Lgr5 positive cells, which were actively proliferating on the base of crypts, became significantly reduced compared with the normal control group, and there was nearly no existing Lgr5 positive cells. However, after infusion of MSC-CMIR, Lgr5 positive intestinal stem cells were significantly increased compared with the radiation group, while in the radiation+MSCNOR group, there was no significant increase in Lgr5 positive intestinal stem cells. (2) On the 3rd day after radiation injury, Bmi1 positive intestinal stem cells were almost invisible. After infusion of MSC-CMIR, Bmi1 positive intestinal stem cells increased significantly, and it was observed not only in the +4 cell position but also in the common position used to be Lgr5 stem cells, indicating that Bmi1 stem cells could differentiate into Lgr5 positive cells to act its repairing effect. (3) Western blot and qRT-PCR further confirmed that the radiation+MSC-CMIR group was significantly higher on the Lgr5 expression level than the radiation group and the radiation+MSC-CMNOR group, and it returned to the normal level on the 7th day after the continuous high expression level. The repair effect of radiation+MSC-CMNOR group was weaker, and only on the 7th day, the expression level of Lgr5 was statistically different from the radiation group. To conclude, inflammation-activated bone marrow MSC-CM exert a protective effect on the small intestinal epithelial stem cells after acute radiation-induced intestinal 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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Identification of proliferation and differentiation capability of hippocampal neural stem/progenitor cells by adherent culture Hu Yuting, Liu Fei, Liu Jing, Tao Xinrong 2019, 23 (9):  1330-1335.  doi: 10.3969/j.issn.2095-4344.1592 Abstract ( 366 )   PDF (695KB) ( 172 )   Save BACKGROUND: In vitro isolation and culture of neural stem/progenitor cells will provide a good cell model for the study of neurodevelopment, neurological diseases, and neural transplantation.  OBJECTIVE: To study the highly effective method for isolation and expansion of hippocampal neural stem/progenitor cells from newborn mice, and to identify the proliferation and differentiation of hippocampal neural stem/progenitor cells using improved adherent culture method. METHODS: Neural stem/progenitor cells were isolated from the hippocampus of newborn C57BL/6 mice and were expanded for several passages. Combination of polylysine and laminin were used for adherent culture to promote cell attachment. Morphological observation and immunofluorescence cytochemical staining were conducted to detect the expression of neural progenitor-specific marker protein Nestin and proliferation index Ki-67. After 7 days of induction and differentiation, the expression of GFAP, DCX, Tuj1 and S100β was detected by immunofluorescence. RESULTS AND CONCLUSION: About 82% of the cultured neural stem/progenitor cells expressed Nestin, and about 49% expressed Ki-67. A small number of cells were DCX-positive neurons after induction and differentiation, while most of the cells were positive for GFAP. The ratio of neurons to astrocytes was 1:1.7 identified by Tuj1 and S100β double staining. The neural stem/progenitor cells derived from the hippocampus were efficiently isolated and cultured. The cell proliferation and differentiation abilities were effectively identified after adherent culture, which can provide sufficient cell sources for further experimental research. 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 and mechanism of fasudil on proliferation and differentiation of neural stem cells Sun Wanying, Tang Ying, Chen Meijuan 2019, 23 (9):  1336-1341.  doi: 10.3969/j.issn.2095-4344.1638 Abstract ( 439 )   PDF (726KB) ( 141 )   Save BACKGROUND: The self-repairing ability of damaged brain and spinal cord is limited. It is important to search for potential therapeutics to promote the proliferation and differentiation of neural stem cells.  OBJECTIVE: To investigate the effect of fasudil on the proliferation and differentiation of primary cultured neural stem cells and its potential mechanism.  METHODS: Neural stem cells were obtained from the brain tissue of 15-day-old fetal rats in vitro. The expression of Nestin in the cells was detected by immunofluorescence. After treatment with fasudil at different concentrations (50, 100, 200 µmol/L) for 24, 48 and 72 hours, the proliferation rate of neural stem cells was detected by MTT, and the apoptosis rate was detected by flow cytometry. After further treatment with autophagy inhibitor, necrosis inhibitor, apoptosis inducer and ferroptosis inducer, the proliferation rates of neural stem cells were detected by MTT and the levels of malondialdehyde were detected by biochemical method. The expression of Nestin, doublecortin, microtubule- associated protein and glial fibrillary acidic protein in neural stem cells were detected by western blot and immunofluorescence after treatment with 200 µmol/L fasudil for 10 days. RESULTS AND CONCLUSION: The positive expression of Nestin protein in primary cultured neural stem cells was observed. The proliferation rate of neural stem cells increased gradually with the increase of fasudil concentration as well as with the prolongation of action time (P < 0.05). Both apoptosis inhibitor and ferroptosis inhibitor can increase the proliferation rate of neural stem cells (P < 0.05). Fasudil increased the proliferation rate of neural stem cells treated by apoptosis inducer and ferroptosis inducer (P < 0.05). Fasudil and ferroptosis inhibitors both decreased the level of malondialdehyde in neural stem cells, while ferroptosis inducers increased the level of malondialdehyde in neural stem cells (P < 0.05). After treatment with fasudil, the expression of doublecortin and glial fibrillary acidic protein protein in neural stem cells increased, and the expression of Nestin decreased (P < 0.05). To conclude, fasudil can improve the survival of neural stem cells by inhibiting apoptosis and ferroptosis, and moreover, it can promote the proliferation and differentiation of neural stem cells into neuron-like cells and glial 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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RNA interferes with Id2 gene expression to inhibit proliferation and invasion of PC-3 prostate cancer stem cells Zhang Yingying, Wang Yinglei, Meng Lin, Xiao Lin, Li Zhonghai, Zhao Zhankui, Wu Houke 2019, 23 (9):  1342-1348.  doi: 10.3969/j.issn.2095-4344.1623 Abstract ( 356 )   PDF (751KB) ( 128 )   Save BACKGROUND: The Id2 gene is an endogenous negative regulator of basic helix-loop-helix factor, which is involved in the cell proliferation, differentiation and existence. Id2 also shows functional diversity in the progression and infiltration of different types of tumors OBJECTIVE: To observe the changes of proliferation and invasiveness of PC-3 human prostate cancer stem cells after shRNA-Id2 transfection. METHODS: PC-3 human prostate cancer stem cells in logarithmic growth phase were harvested to isolate tumor stem cell spheres by serum-free suspension culture. The expression of CD44+CD24- on the surface of tumor stem cells was detected by flow cytometry. The shRNA-Id2 expression vector was constructed and transfected into PC-3 human prostate cancer stem cells. Untransfected PC-3 human prostate cancer stem cells were used as control. At 48 hours after transfection, the expression of Id2 gene and protein in shRNA-Id2 transfected prostate cancer stem cells, NC-shRNA empty vector transfected prostate cancer stem cells and untransfected prostate cancer stem cells were detected by RT-PCR and western blot, respectively. The proliferation and invasion of shRNA-Id2 transfected prostate cancer stem cells and untransfected prostate cancer stem cells were detected by MTT assay and Transwell chamber, respectively. The expressions of E-cadherin, vimentin and Twist were detected by western blot and RT-PCR. RESULTS AND CONCLUSION: Tumor stem cell spheres were successfully isolated by the serum-free suspension culture. The expression rate of CD44+CD24- on the surface of the third-generation PC-3 human prostate cancer stem cells was (85.69±8.96)%, indicating that the cultured tumor stem cell spheres overexpressed the phenotype of tumor stem cells. At 48 hours after transfection, the expression of Id2 gene and protein was significantly lower in the shRNA-Id2 transfection group than the non-transfection group (P < 0.05), indicating that the expression of Id2 was successfully interfered with the expression of PC-3 prostate cancer stem cells. The invasive ability of the cells in the shRNA-Id2 transfection group was significantly lower than that in the non-transfection group (P < 0.05). Western blot and RT-PCR detection showed that the expression of E-cadherin, an epithelial marker of PC-3 prostate cancer stem cells, in the shRNA-Id2 transfection group was significantly higher than that in non-transfection group (P < 0.05), while the expression of vimentin, a marker of mesenchymal stem cells, and Twist, a transcription factor regulating cell-mesenchymal transformation, in the shRNA-Id2 transfection group was significantly lower than that in the non-transfection group (P < 0.05). These findings indicate that RNA interference with Id2 gene can inhibit the proliferation and invasion of PC-3 prostate cancer stem cells by regulating the expression of E-cadherin, vimentin and Twist. 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-10b regulates aldehyde dehydrogenase 1 mRNA and protein expression in breast cancer MCF-7 cell line Han Mingli, Lü Pengwei, Qian Xueke, Yang Xue, Yang Yunqing, Gu Yuanting 2019, 23 (9):  1349-1353.  doi: 10.3969/j.issn.2095-4344.1622 Abstract ( 463 )   PDF (553KB) ( 92 )   Save BACKGROUND: MicroR-10b can regulate the characteristics of breast cancer stem cells, and acetaldehyde dehydrogenase 1 (ALDH1) is one of the most important markers of breast cancer stem cells. The interaction between them in breast cancer cells needs further explorations. OBJECTIVE: To investigate whether over-expression of microRNA-10b affects ALDH1 mRNA and protein levels in human breast cancer MCF-7 cells. METHODS: hsa-miR-10b mimics or its negative control was transfected into breast cancer MCF-7 cell line. At 48 hours after transfection, the mRNA and protein expression of ALDH1 in the cells was detected using real-time RT-PCR and western blot assays, respectively. RESULTS AND CONCLUSION: Over-expression of microR-10b was found in the MCF-7 cell line transfected with hsa-miR-10b mimics, which was significantly higher than that in the control group (P=0.003 47). Both of ALDH1 mRNA and protein levels were up-regulated in the MCF-7 cell line overexpressing microR-10b, as compared with the control group (P=0.009 54 and P=0.003 11, respectively). To conclude, over-expression of microR-10b induces the ALDH1 mRNA and protein expression in the breast cancer MCF-7 cell line, providing new evidence that microR-10b regulates the invasion and metastasis of breast 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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Time-dose effects of Taohong Siwu Decoction on number and functional activity of peripheral blood endothelial progenitor cells Wang Xiaobin, Jiang Hongxin, Qu Changhong, Wu Dongmei, Zhang Rongsheng, Xu Bin 2019, 23 (9):  1354-1358.  doi: 10.3969/j.issn.2095-4344.1593 Abstract ( 298 )   PDF (628KB) ( 203 )   Save BACKGROUND: Recent studies have shown that Taohong Siwu Decoction can alleviate the damage of vascular endothelial cells and maintain their normal secretory function, and endothelial progenitor cells can promote the repair of endothelial injury. Therefore, it is assumed that Taohong Siwu Decoction may protect endothelial function by improving the functional activity and increasing the number of endothelial progenitor cells. OBJECTIVE: To investigate whether Taohong Siwu Decoction can augment the number and functional activity of peripheral blood endothelial progenitor cells.  METHODS: Endothelial progenitor cells were isolated from the peripheral blood of healthy subjects, and divided into control, low-, moderate- and high-concentration Taohong Siwu Decoction groups. Cells were then cultured to observe the dose-effect relationship within 24 hours. Meanwhile, the high-concentration Taohong Siwu Decoction group was cultured for respective time points (6, 12, 24 and 48 hours) for observing the time-effect relationship. The number of endothelial progenitor cells was counted under inverted phase contrast microscope. Proliferation, adhesion and migration of endothelial progenitor cells were detected by MTT chromatometry, adhesion activity assay and modified Boyden chamber assay, respectively.  RESULTS AND CONCLUSION: (1) The proliferation, adhesion and migration abilities of endothelial progenitor cells in the Taohong Siwu Decoction groups were significantly higher than those in the control group and showed a certain dose-effect relationship. (2) The proliferation, adhesion and migration abilities of endothelial progenitor cells in the Taohong Siwu Decoction groups were enhanced in a time-dependent manner, especially at 24 hours after intervention (P < 0.01). To conclude, the Taohong Siwu Decoction can increase the number of endothelial progenitor cells and promote cell functions. High-concentration Taohong Siwu Decoction exhibits the best interventional effect at 24 hours after intervention. 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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Osteogenic induction and identification of mammary stem cells derived from a Holstein dairy cow Chen Yumeng, Han Zhexian, Liu Yingchun, Gao Feng 2019, 23 (9):  1359-1363.  doi: 10.3969/j.issn.2095-4344.1643 Abstract ( 374 )   PDF (655KB) ( 131 )   Save BACKGROUND: The isolated and purified mammary stem cells from Holstein dairy cows have been induced to differentiate into nerve cells, adipocytes and osteoblasts, further enriching their multi-directional differentiation potential, which is of great significance for the study on mammary stem cells. OBJECTIVE: To investigate the osteogenic potential of mammary stem cells from Holstein dairy cows. METHODS: Mammary stem cells from Holstein dairy cows were isolated and purified, which were provided by the Key Laboratory of Biological Manufacturing of Inner Mongolia Autonomous Region. The fourth generation of mammary stem cells were cultured for 21 days in an osteogenic induction medium, and identified by alizarin red staining and RT-PCR. RESULTS AND CONCLUSION: After osteogenic induction, the cell edge was indistinct, and there were some granular calcified nodules in the cells. The induced cells were positive for alizarin red staining. The positive expressions of Alpl and Bglap in the induced osteoblasts were detected, indicating that the mammary stem cells from Holstein dairy cows have the potential to differentiate into osteoblasts. 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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Adipose-derived stem cell transplantation for acute kidney injury caused by crush injury Sun Heyuan, Yan Weiqing 2019, 23 (9):  1364-1369.  doi: 10.3969/j.issn.2095-4344.1591 Abstract ( 466 )   PDF (857KB) ( 122 )   Save BACKGROUND: Adipose-derived stem cells have the advantages of easy access, easy separation, small trauma, and rapid proliferation. Current treatments for kidney injury are more limited, and adipose-derived stem cells may provide a new treatment route. OBJECTIVE: To investigate the effects of adipose-derived stem cell transplantation on the kidney function of rats with acute kidney injury induced by crush injury in rats.  METHODS: Cryopreserved adipose-derived stem cells were recovered in vitro and cultured to prepare cell suspension following labeling with PKH-26. Twenty rats were randomly selected from 66 experimental Sprague-Dawley rats (provided by Beijing Vital River Laboratory Animal Technology Co., Ltd.) as normal control group. In the 40 of the remaining 46 rats, a pathological model of acute kidney injury caused by compression injury was successfully established by the use of forceps to double the proximal hind limbs. The 40 rat models were divided into model group and cell transplantation group, with 20 rats in each group. After 6 hours of modeling, the rats in the model group were given intravenous injection of normal saline (20 μL), and the rats in the cell group were given intravenous injection of PKH-26-labeled adipose-derived stem cells (20 μL, 3×106/L), once a day for 3 continuous days. The levels of serum creatinine and urea nitrogen were measured in each group at 1, 3, 14 and 21 days after transplantation. The left kidney of the rats in each group was observed using hematoxylin-eosin staining, TUNEL staining, RT-PCR and western blot assay at 3 and 21 days after cell transplantation.  RESULTS AND CONCLUSION: (1) The levels of creatinine and urea nitrogen in the serum of rats at 1, 3, 14 and 21 days after cell transplantation were significantly higher in the model group than the normal control group (P < 0.05) and cell transplantation group (P < 0.05). (2) At 3 and 21 days after cell transplantation, the scores on the kidney injury and apoptotic rate of kidney cells were ranked as follows: model group > cell transplantation group > normal control group, and there were significant differences between groups (P < 0.05). (3) At 3 and 21 days after cell transplantation, the expressions of bax and Caspase-3 in the kidney tissue at mRNA and protein levels were significantly higher in the model group and cell transplantation than the normal control group (P < 0.01) as well as significantly higher in the cell transplantation group than the model group (P < 0.05). To conclude, adipose-derived stem cell transplantation has obvious repairing effect on acute kidney injury caused by crush injury, and its mechanism may be related to the involvement of adipose-derived stem cells in regulating the expression of bax and Caspase-3. 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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Erythropoietin preconditioned adipose-derived mesenchymal stem cell transplantation for treating diabetic nephropathy in rats Wang Disheng, Kong Liusha, Wang Jia, Li Xia 2019, 23 (9):  1370-1376.  doi: 10.3969/j.issn.2095-4344.1601 Abstract ( 541 )   PDF (791KB) ( 140 )   Save BACKGROUND: Studies have confirmed that the occurrence and development of diabetic nephropathy are related to tubular epithelial cell transdifferentiation and renal interstitial fibrosis. OBJECTIVE: To investigate the protective effect of erythropoietin preconditioned adipose-derived mesenchymal stem cells on diabetic nephropathy rat’s kidney and to evaluate its potential mechanisms. METHODS: Human adipose-derived mesenchymal stem cells were harvested and identified for cell multilineage differentiation. TranswelI migration system was used to observe the effects of erythropoietin of different concentrations (0, 5, 20, 50 IU/mL) on the migration of adipose-derived mesenchymal stem cells to high glucose-induced rat renal tubular epithelial cell lines. Forty-eight Sprague-Dawley rats (provided by the Animal Experimental Center of Xuzhou Medical University in China) were randomly divided into normal control, diabetic model group, cell transplantation group and erythropoietin preconditioning group (n=12 per group). Adipose-derived mesenchymal stem cells (3.5×105, 150 μL) alone or erythropoietin (20 IU/mL) preconditioned adipose-derived mesenchymal stem cells were injected into the tail vein of rats in the latter two groups, respectively. The protein levels of transforming growth β1, α-smooth muscle actin, E-cadherin, matrix metalloproteinase-9 and matrix metalloproteinase inhibitor-1 in the renal tissues were detected by western blot assay at 14 weeks after cell transplantation. RESULTS AND CONCLUSION: Erythropoietin preconditioning markedly increased the number of migrated adipose-derived mesenchymal stem cells in a concentration-dependent manner (P < 0.05), and the ability peaked at a concentration of 20 IU/ml. The expression of stromal cell-derived factor-1 protein in NRK-52E cells was consistent with the migration trend of adipose-derived mesenchymal stem cells. Compared with the diabetic model group, the levels of transforming growth β1, α-smooth muscle actin, and matrix metalloproteinase inhibitor-1 were increased dramatically, while the levels of E-cadherin and matrix metalloproteinase-9 decreased remarkably in the other groups (P < 0.05), especially in erythropoietin preconditioning group (P < 0.05). In conclusion, erythropoietin could promote the directional chemotaxis of adipose-derived mesenchymal stem cells, and moreover, adipose-derived mesenchymal stem cells could inhibit the transdifferentiation of renal tubular epithelial cells, reduce the deposition of extracellular matrix and delay the progression of diabetic renal fibrosis under the action of erythropoietin. 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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Biological characteristics of three kinds of human placenta-derived mesenchymal stem cells Wang Liudi, Liu Wei, Xie Yuanyuan, Gao Tianyun, Huang Feifei, Wang Bin 2019, 23 (9):  1377-1383.  doi: 10.3969/j.issn.2095-4344.1600 Abstract ( 456 )   PDF (938KB) ( 157 )   Save BACKGROUND: The placental tissue structure is complex, including the amniotic membrane, chorion, and decidua from the mother. Mesenchymal stem cells derived from different tissues of the same placenta have been reported to have similar biological characteristics. To date, there is no study regarding quantitative comparison of differentiation potential and immunomodulatory function of mesenchymal stem cells derived from different tissues of human placenta. OBJECTIVE: To investigate the biological characteristics including differentiation potential and immunomodulatory function of mesenchymal stem cells derived from different tissues of human placenta. METHODS: The amnion-, chorion-, and decidua-derived mesenchymal stem cells were isolated from the placental tissue of a baby boy by enzymatic digestion method. The biological characteristics of these three kinds of mesenchymal stem cells were systematically investigated including cell morphology, immunophenotypes, karyotypeanalysis, adipogenic and osteogenic differentiation potential, and Treg cells proliferation capacity. RESULTS AND CONCLUSION: All three kinds of mesenchymal stem cells showed fibroblast-like morphology and expressed the surface markers of mesenchymal stem cells with high expressions of CD73, CD90 and CD105, as well as low expressions of CD14, CD19, CD34, CD45 and HLA-DR. The karyotypes of the amnion- and chorion-derived mesenchymal stem cells were the same as the fetus, and decidua-derived mesenchymal stem cells had the same karyotype as the mother. There were significant differences in adipogenic differentiation capacity between three kinds of mesenchymal stem cells (amnion-derived mesenchymal stem cells > chorion-derived mesenchymal stem cells > decidua-derived mesenchymal stem cells; P < 0.05). In contrast, the osteogenic differentiation capacity of amnion-derived mesenchymal stem cells was remarkably higher than that of decidua-derived mesenchymal stem cells (P < 0.05). The amnion- and chorion-derived mesenchymal stem cells had the higher potential of Treg cell proliferation induction than decidua-derived mesenchymal stem cells. These findings indicate that three sources of human placenta-derived mesenchymal stem cells have different karyotypes, adipogenic and osteogenic differentiation potential, and immunomodulatory capability, providing a variety of ideal seed cell sources for disease treatment. 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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Hepatocyte-like cells derived from induced pluripotent stem cells inhibit liver fibrosis in rats Cheng Gang, Huang Denggao, Liang Ying 2019, 23 (9):  1384-1389.  doi: 10.3969/j.issn.2095-4344.1607 Abstract ( 393 )   PDF (774KB) ( 173 )   Save BACKGROUND: Induced pluripotent stem cells have similar self-renewal, proliferation and differentiation abilities to embryonic stem cells. They have no source limitations, no ethical problems, and no current problems of cell xenogenesis, which are expected to be the source of cells for the treatment of liver diseases. OBJECTIVE: To observe the effect of induced pluripotent stem cell-derived hepatocyte-like cells on liver fibrosis. METHODS: The three-step method in vitro was used to induce the differentiation of induced pluripotent stem cells into hepatocyte-like cells. Glycogen staining, immunohistochemistry and low-density lipoprotein uptake assay were used to detect the ability of induced cells to synthesize glycogen, alpha-fetoprotein, albumin, CK18 protein and low-density lipoprotein uptake. Forty-five Sprague-Dawley rats (provided by the Experimental Animal Center, the Affiliated Haikou Hospital, Xiangya School of Medicine, Central South University) were randomized into three groups: normal control group, model group and cell transplantation group (n=15 per group). The rats in the latter two groups were intraperitoneally injected with carbon tetrachloride to establish liver fibrosis models. Cell transplantation group was given intravenous injectin of hepatocyte-like cells (induced for 21 days), 0.5 mL, 2×109/L, at 3 days after modeling. Four weeks after cell transplantation, venous blood and liver tissue samples were taken to analyze the changes of liver function, liver fibrosis index and liver pathology. RESULTS AND CONCLUSION: (1) After 21 days of induction, human induced pluripotent stem cell clonal clusters became loose, mainly round or polygonal in shape, and presented with a dense paving stone-like arrangement. A large amount of pink glycogens could be seen in the cytoplasm, indicating that induced pluripotent stem cells have the ability to synthesize glycogen. Low-density lipoprotein uptake test showed that induced pluripotent stem cells had the ability to uptake low-density lipoprotein. Immunohistochemistry detection showed that the cells were positive for alpha fetoprotein, albumin and CK18. (2) At 4 weeks after cell transplantation, the level of albumin in the model group was significantly lower than that in the normal control group (P < 0.05), while the levels of direct bilirubin, indirect bilirubin, aspartate aminotransferase, alanine aminotransferase, type IV collagen, serum hyaluronidase, serum type III procollagen in the model group were significantly higher than those in the normal control group (P < 0.05). Compared with the model group, the level of albumin in the cell transplantation group was significantly increased (P < 0.05), while the levels of direct bilirubin, indirect bilirubin, aspartate aminotransferase, alanine aminotransferase, type IV collagen, serum hyaluronidase, serum type III procollagen in the cell transplantation group were significantly decreased (P < 0.05). (3) Four weeks after cell transplantation, inflammatory cell infiltration, hepatocyte degeneration and necrosis in the cell transplantation group were improved to different extents. Therefore, hepatocyte-like cells derived from induced pluripotent stem cells could significantly improve liver fibrosis 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 rhubarb-free anthraquinone in the treatment of acute pancreatitis with adipose-derived stem cell transplantation in rats Zheng Junjie, Tian Weijun, Wang Jinfeng, Ye Kui 2019, 23 (9):  1390-1396.  doi: 10.3969/j.issn.2095-4344.1612 Abstract ( 403 )   PDF (949KB) ( 148 )   Save BACKGROUND: Studies have shown that rhubarb-free anthraquinone can protect the stability of the intestinal mucosa cell structure and function. However, the combination of rhubarb-free anthraquinone with adipose-derived stem cells to treat acute pancreatitis in rats has not yet been reported. OBJECTIVE: To investigate the effects of rhubarb-free anthraquinone on the treatment of acute pancreatitis by fat stem cell transplantation in rats. METHODS: Cryopreserved mouse adipose-derived stem cells (provided by the Chinese Academy of Medical Sciences) were rapidly recovered and cultured in vitro. The survival cells were labeled using PKH-26, and then the cell survival rate of adipose-derived stem cells was determined by MTT colorimetry. Sprague-Dawley rats provided by Beijing Vital River Laboratory Animal Technology Co., Ltd. were equally randomized into four groups. Animal models of acute pancreatitis were made in all rats through intestinal wall puncture for retrograde administration of 5% sodium taurocholate to the pancreaticobiliary tube, and then the model rats were given tail vein injection of L-DMEM complete medium (0.5 mL) in the model group, intragastric administration of 200 mg/kg rhubarb-free anthraquinone in the rhubarb-free anthraquinone group, tail vein injection of adipose-derived stem cells (1×107 cells/L, 0.5 mL) in the cell transplantation group, and intragastric administration of 200 mg/kg rhubarb-free anthraquinone plus tail vein injection of 1×107 adipose-derived stem cells (0.5 mL) in the combined treatment group. All interventions in each group were performed once a day, for 3 continuous days.  RESULTS AND CONCLUSION: (1) The levels of serum amylase and interleukin-6 were significantly reduced in the rhubarb-free anthraquinone group and cell transplantation group compared with the model group (P < 0.05), while the level of trypsinogen activation peptide significantly increased (P < 0.05). In the combined treatment group, the levels of three indicators mentioned above were significantly decreased compared with the rhubarb-free anthraquinone group and cell transplantation group (P < 0.05). (2) The results of hematoxylin-eosin staining showed that the pathological changes in the pancreatic tissue of rats were significantly reduced in the rhubarb-free anthraquinone group and cell transplantation group, such as fatty degeneration, hemorrhage, cell necrosis and inflammatory cell infiltration. The remission of pathological changes was more obvious in the combined treatment group. (3) The number of positive cells labeled by PKH-26 was the highest in the combined treatment group, followed by the cell transplantation group, while there were no PKH-26-positive cells in the rhubarb-free anthraquinone group and model group (P < 0.05). (4) Compared with the model group, the number of apoptotic cells in the pancreatic tissue was significantly reduced in the rhubarb-free anthraquinone group and cell transplantation group, and lowest in the combined treatment group (P < 0.01). (5) The expression of transforming growth factor-β1 and Smad2/3 at gene and protein levels was highest in the model group, followed by the rhubarb-free anthraquinone group and cell transplantation group (P < 0.05), and lowest in the combined treatment group (P < 0.01). To conclude, the combined intervention of rhubarb-free anthraquinone and adipose-derived stem cell transplantation could effectively improve the blood biochemical index level in the rats with acute pancreatitis, significantly relieve the degree of inflammatory response, pancreatic tissue morphology, and apoptosis of pancreatic cells, which may be related to the reduction of the transforming growth factor-β/Smad signal 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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Bone marrow mesenchymal stem cell transplantation in a rat model of thin endometrium based on HOXA10 regulatory network Wang Yifei, Song Yang, Guan Yongge, Xu Chunyan 2019, 23 (9):  1397-1402.  doi: 10.3969/j.issn.2095-4344.1605 Abstract ( 487 )   PDF (765KB) ( 141 )   Save BACKGROUND: Thin endometrial diseases are a challenge in clinical treatment at present. Scholars have found that bone marrow mesenchymal stem cells (BMSCs) transplantation has its unique curative effect and advantages, but few studies have been conducted on pathway or gene control. OBJECTIVE: To observe the effect of BMSCs transplantation in rats with thin endometrium based on the HOXA10 regulatory network.  METHODS: Twenty-one adult female Sprague-Dawley rats of SPF grade (provided by the Animal Experimental Center, Guangzhou University of Chinese Medicine in China) were randomly divided into three groups (n=7/group): control group, model group, and BMSCs group. In the latter two groups, a thin endometrium model was prepared in each rat by filling the uterine cavity with 95% ethanol. In the control group, normal saline was injected to fill the uterine cavity of rats. After extraction of ethanol or normal saline, the rats in the BMSCs group were injected intrauterinely with 1 mL of BMSCs suspension (1×1010 cells/L), and those in the control and model groups were given the same volume of normal saline. After two estrous cycles, the uterus of each rat was removed. Hematoxylin-eosin staining was used to measure the thickness of the endometrium. Immunohistochemistry was used to detect the expression of vimentin, keratin, vascular endothelial growth factor, leukemia inhibitory factor and integrin αvβ3. qRT-PCR was used to detect the relative transcription of HOXA10 and miR-196b. RESULTS AND CONCLUSION: (1) Compared with the control group, the endometrial thickness of the rats were significantly thinner in the model and BMSCs groups (P < 0.05), while the endometrial thickness in the BMSCs group was thicker than that in the model group (P < 0.05). (2) The mean absorbance values of endometrial vimentin, keratin, vascular endothelial growth factor, leukemia inhibitory factor and integrin αvβ3 were highest in the control group, higher in the BMSCs group and lowest in the model group, and there were significant differences between groups (P < 0.05). (3) The relative transcript level of HOXA10 gene in the model and BMSCs group was significantly lower than that in the control group, while the relative transcript level of HOXA10 gene in the BMSCs group was significantly higher than that in the model group (P < 0.05). The relative transcript level of miR-196b in the model and BMSCs groups was significantly higher than that in the control group (P < 0.05), while the relative transcript level of miR-196b in the BMSCs group was lower than that in the model group (P < 0.05). (4) HOXA10 was negatively correlated with miR-196b gene, HOXA10 was positively correlated with the protein expression to different extents, and miR-196b gene was negatively correlated with the protein expression to different extents. These findings suggest that BMSCs transplantation can improve the endometrial thickness and relevant protein levels of thin endometrium rats to some extent, which may be attributed to the negative regulation of HOXA10 gene by miR-196b, and HOXA10 gene further promotes the expression of vascular endothelial growth factor, leukemia inhibitory factor and integrin αvβ3 proteins. 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 induced pluripotent stem cell transplantation for acute lung injury in rats Liu Shenggang, Yang Hongzhong, He Baimei 2019, 23 (9):  1403-1409.  doi: 10.3969/j.issn.2095-4344.1608 Abstract ( 287 )   PDF (836KB) ( 220 )   Save BACKGROUND: Embryonic stem cells and mesenchymal stem cells are two main cell sources for stem cell transplantation in the treatment of acute lung injury. There are few reports on the study of autologous induced pluripotent stem cells in the treatment of acute lung injury. OBJECTIVE: To investigate the possibility of induced pluripotent stem cells derived from autologous dermal fibroblasts injected through the caudal vein in the treatment of acute lung injury in rats. METHODS: Twenty-four Sprague-Dawley rats (provided by Beijing Vital River Laboratory Animal Technology Co., Ltd.) were randomly divided into three groups. The control group was intraperitoneally injected with normal saline, and the model group and the experimental group were intraperitoneally injected with lipopolysaccharide to make acute lung injury models in rats. At 24 hours after modeling, phosphate buffer solution was injected into the tail vein of the rats in the control and model groups, while the rats in the experimental group were given induced pluripotent stem cell suspension by the tail vein. The changes of lung tissue morphology, lung wet/dry weight ratio, pathological injury score, serum interleukin 1beta, interleukin 6 and tumor necrosis factor alpha levels were observed at 7 days after treatment. RESULTS AND CONCLUSION: (1) At 7 days after treatment, pulmonary interstitial edema, alveolar septum thickening, inflammatory cell infiltration, capillary congestion, irregular alveolar morphology, and exudate in the alveolar cavity were significantly improved in the experimental group. (2) At 7 days after treatment, the wet/dry weight ratio of lung tissue in the model and experimental groups was significantly higher than that in the control group, but the wet/dry weight ratio of lung tissue and pathological injury score in the experimental group were significantly lower than those in the model group (P < 0.01).(3) At 7 days after treatment, the levels of serum interleukin 1beta, interleukin 6 and tumor necrosis factor alpha were ranked as follows: model group > experimental group > control group, and there were significant differences between groups (P < 0.01). To conclude, the transplantation of induced pluripotent stem cells derived from autologous dermal fibroblasts can effectively alleviate acute lung injury and reduce serum inflammatory factor levels 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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Synergistic promotion of inflammatory chondrocyte reverse differentiation by the combination of curcumin and magnesium sulfate Wang Yang, Song Zhuoyue, Li Guangheng 2019, 23 (9):  1410-1415.  doi: 10.3969/j.issn.2095-4344.1594 Abstract ( 411 )   PDF (825KB) ( 123 )   Save BACKGROUND: Osteoarthritis is a common cause of pain and disability in the elderly. The underlying cause is the combination of inappropriate mechanical stress, inflammatory mediators and biochemical factors. Curcumin has been shown to have anti-oxidant, anti-inflammatory, anti-bacterial, anti-tumor, neuroprotective, and cardioprotective effects, radiation protection and therapeutic effects on osteoarthritis. Similarly, magnesium sulfate can relieve joint pain and inhibit joint destruction. OBJECTIVE: To investigate the mechanism by which the combined use of curcumin and magnesium sulfate exerts synergistic effect to promote inflammatory chondrocyte reverse differentiation. METHODS: Primary cultured inflammatory chondrocytes were subjected to monolayer culture in vivo. Cell proliferation assay (MTS) was used to detect the proliferation of inflammatory chondrocytes under in vitro monolayer culture conditions. The experimental cells were divided into four groups and underwent 3D induced reverse differentiation culture for 18 days: single culture of chondrocytes (chondrocyte group), inflammatory chondrocyte cultured with curcumin (curcumin group), inflammatory chondrocytes cultured with magnesium sulfate (magnesium sulfate group), and inflammatory chondrocytes cultured with curcumin and magnesium sulfate (combination group).  RESULTS AND CONCLUSION: MTS proliferation experiments showed that inflammatory chondrocytes at passage 3 had a higher rate of early proliferation and a lower degree of differentiation. Quantitative PCR results showed that the mRNA levels of type II collagen, proteoglycan and SOX9 were significantly higher in the combination group than in the curcumin group or magnesium sulfate group (P < 0.01). The size of the gross specimens and the positive area of chondrocyte reverse differentiation for alcian blue staining and safranin O staining in the combination group were significantly larger than those in the other three groups (P < 0.01). TUNEL staining results indicated that the positive area of apoptosis-specific staining in the combination group and magnesium sulfate group was significantly smaller than that in the other two groups (P < 0.01). Therefore, the combined use of curcumin and magnesium sulfate has the synergistic effect to promote the reverse differentiation of inflammatory chondrocytes. 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 adipose-derived mesenchymal stem cell transplantation via the tail vein for acute liver failure in rats Zhang Deguo, Tan Xueying, Tang Nan, Huang Fei, Shi Guangjun 2019, 23 (9):  1416-1421.  doi: 10.3969/j.issn.2095-4344.1630 Abstract ( 321 )   PDF (820KB) ( 106 )   Save BACKGROUND: Mesenchymal stem cells can protect and repair the liver of rats with liver failure, but the mechanisms are not completely clear. OBJECTIVE: To explore the protective effects and related mechanisms of intravenous injection of human adipose-derived mesenchymal stem cells on acute liver failure in rats. METHODS: Thirty-six Sprague-Dawley rats (provided by Qingdao Daren Fucheng Animal Husbandry Co., Ltd. in China) were randomly divided into control group, model group and transplantation group. Animal models of acute liver failure were established by intraperitoneal injection of D-galactosamine in the model group and the transplantation group. One day after modeling, the rats in the transplantation group were injected with human adipose-derived mesenchymal stem cell suspension, and those in the model group were injected with the same amount of saline. After 1 and 3 days of cell transplantation, the serum levels of alanine aminotransferase, aspartate aminotransferase, and total bilirubin were measured. Three days after cell transplantation, the serum levels of tumor necrosis factor-α, interleukin-6 and interleukin-10 were detected, the pathological changes of the rat liver were observed by hematoxylin-eosin staining, and the activity of glycogen synthase kinase-3β protein in the liver tissue was detected by western blot. RESULTS AND CONCLUSION: Compared with the model group, there was a significant reduction in the serum levels of alanine aminotransferase, aspartate aminotransferase, total bilirubin, tumor necrosis factor-α, interleukin-6 and interleukin-10 in the transplantation group (P < 0.05). Inflammation and necrosis of liver tissues in the transplant group were alleviated compared with the model group. The activity of glycogen synthase kinase 3β in the liver tissue of the transplanted group was lower than that of the model group (P < 0.05). Overall, these results indicate that human adipose-derived mesenchymal stem cells can alleviate hepatic inflammation and pathological injury, and improve the liver function in rats with acute hepatic failure. Moreover, the mechanism may be related to the inhibition of glycogen synthase kinase 3β activity. 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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Therapeutic effects of hepatocyte transplantation via two different intrasplenic approaches in acute hepatic failure rats Feng Yuan, Li Dewei, Yang Junjun 2019, 23 (9):  1422-1427.  doi: 10.3969/j.issn.2095-4344.1624 Abstract ( 391 )   PDF (755KB) ( 158 )   Save BACKGROUND: Hepatocyte transplantation has achieved some success in animal experiments for the treatment of metabolic diseases and acute liver failure. However, the clinical efficacy of hepatocyte transplantation is unsatisfactory. The difference between the experimental results and the clinical efficacy may be related to the hepatocyte transplantation approach. OBJECTIVE: To evaluate the therapeutic effects of hepatocyte transplantation by the intubation via the intubation of the splenic artery and intrasplenic injection in rats with acute hepatic failure, providing more optimal transplantation approaches and methods. METHODS: Hepatocytes were isolated and cultured by the modified Seglen’s method (two-step). Acute hepatic failure was induced by D-gal in Sprague-Dawley rats (provided by the Experimental Animal Center of Chongqing Medical University in China). After 24 hours, an intubation tube was inserted into the splenic artery in 65 rats with acute hepatic failure, which was successful in 60 rats. Then these 60 rat models were randomly divided into three groups (n=20 per group). Intrasplenic injection group received about 2×107 hepatocytes through intrasplenic injection and 0.4 mL of Hank’s solution through the splenic artery. Splenic artery group received 0.4 mL of Hank’s solution through intrasplenic injection and 2×107 hepatocytes through the splenic artery. Model group received 0.4 mL of Hank’s solution through intrasplenic injection and 0.4 mL of Hank’s solution through the splenic artery. Survival rate and liver function of the rats was observed within 14 days after transplantation. The distribution of CFDA-SE-labeled hepatocytes transplanted via the splenic artery was observed under fluorescence microscope at 7 days after transplantation, and meanwhile, the distribution and proliferation of transplanted hepatocytes in the spleen were observed using hematoxylin-eosin staining. Synthesis of albumin in the spleen was observed by immunofluorescence staining. RESULTS AND CONCLUSION: (1) 80%-90% hepatocytes survived after isolation. (2) At 14 days after transplantation, the survival rates of rats in the three groups were significantly different: intrasplenic injection group > splenic artery group > model group. (3) The liver function of rats was significantly improved in the intrasplenic injection group and the splenic artery group, especially in the former group. (4) CFDA-SE-labeled hepatocytes (green fluorescence) were scattered in the rat spleen and liver at 7 days after transplantation via the splenic artery. (5) At 14 days after transplantation, immunofluorescent staining of albumin demonstrated some positive cells in the rat spleen in the intrasplenic injection group and splenic artery group. (6) At 7 days after transplantation, transplanted hepatocytes were concentrated and colonized in the red pulp of the spleen. In conclusion, hepatocyte transplantation through catheterization of the splenic artery via carotid route can improve the survival of rats with acute hepatic failure and ameliorate the hepatic function, but intrasplenic injection is significantly superior to the injection via the splenic artery. 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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Clinical application of autogenous adipose-derived stromal vascular fraction-assisted fat transplantation in the improvement of facial skin quality Yin Yating, Zhang Aijun, Wang Hao, Wang Pingping, Li Jianhua, Wen Minmin, Jin Peisheng 2019, 23 (9):  1428-1433.  doi: 10.3969/j.issn.2095-4344.1631 Abstract ( 380 )   PDF (837KB) ( 227 )   Save BACKGROUND: Many studies have shown that cell-assisted lipotransfer promotes the survival of fat implants, but there are few studies exploring stromal vascular fraction (SVF)-assisted fat transplantation for improving facial skin quality. OBJECTIVE: To evaluate the clinical effect of autologous adipose-derived SVF-assisted autologous fat transplantation in the improvement of facial skin quality. METHODS: From September 2016 to June 2018, in the Plastic and Cosmetic Center, the Affiliated Hospital of Xuzhou Medical University, 20 patients were recruited and then randomly divided into experimental group and control group, namely SVF-assisted fat transplantation and simple fat transplantation, respectively. A VISIA skin detector was used to detect facial skin quality of patients preoperatively and 6 months postoperatively, including spots, wrinkles, texture, pores, ultraviolet spots, brown spots, couperose skin and porphyrin.  RESULTS AND CONCLUSION: The effect of improvement in wrinkles and texture in the experimental group was better than that of the control group, and the difference was statistically significant (P < 0.05). In terms of spots, pores and couperose skin, the therapeutic effect in the experimental group was better than that in the control group, but the difference was not statistically significant (P > 0.05). There was no significant difference between the two groups in the improvement of ultraviolet spot and brown spots. The porphyrin was not affected by the subjects. To conclude, SVF can promote the effect of fat transplantation in the improvement of facial skin quality. 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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Biological characteristics of stromal cell-derived factor-1/CXC chemokine receptor 4 signal axis Wu Zhouling, Basheer Hamed Hamood AL-Shameri, Ban Guifei, Chen Wenxia 2019, 23 (9):  1434-1440.  doi: 10.3969/j.issn.2095-4344.1590 Abstract ( 464 )   PDF (802KB) ( 121 )   Save BACKGROUND: Nowadays, stromal cell-derived factor-1 (SDF-1)/CXC chemokine receptor 4 (CXCR4) signal axis has been used extensively because of its biological effects and particularly a great progress has been achieved in the mechanism of SDF-1/CXCR4 signal axis as well as in its use for tissue regeneration. OBJECTIVE: To summarize the factors affecting the regulation of SDF-1 and CXCR4 and to review the research progress in the biological characteristics of SDF-1/CXCR4 signal axis. METHODS: The first author searched the PubMed, CNKI, WanFang and VIP databases for relevant articles published from January 1990 to August 2018. The keywords were “tissue engineering; cell homing; chemokine; regeneration; pulp regeneration; HIF-1; SDF-1; CXCL12; CXCR4; NOX-A12” in both Chinese and English. RESULTS AND CONCLUSION: Hypoxia-inducible factor-1 plays a key role in the regulation of SDF-1, and there are multiple factors which can affect the expression of CXCR4. SDF-1/CXCR4 signal axis formed by the combination of SDF-1 and CXCR4 plays an important biological role in various physiological and pathological processes. Blocking SDF-1 is used to inhibit the pathogenic effect of the SDF-1/CXCR4 signal axis for therapeutic purposes, while increasing SDF-1 can strengthen the SDF-1/CXCR4 signal axis and enhance the ability of chemotactic endogenous cell homing for tissue regeneration. To further illustrate the mechanism of the SDF-1/CXCR4 signal axis, we upregulate or downregulate the expression of SDF-1 or CXCR4 by exogenous means to influence the biological function of the signal axis, and thus provide theoretical basis for optimizing clinical treatment strategies, and developing the biological function of the signal axis for human health benefits. 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-derived exosomes for the treatment of neurodegenerative diseases: existing problems and prospects in application Chen Chen, Huang Hui, Hu Wenjia, Li Xiangyong 2019, 23 (9):  1441-1447.  doi: 10.3969/j.issn.2095-4344.1582 Abstract ( 478 )   PDF (736KB) ( 206 )   Save BACKGROUND: Exosomes are nano-scale vesicles that can be secreted by almost all types of cells in the body, which can participate in multiple cell signaling pathways by transporting signal molecules, such as proteins, lipids and miRNAs to perform intercellular communication, immune responses, and antigen presentation. Therefore, exosomes have a great value in the clinical diagnosis and treatment of diseases. Of the cell types known to produce exosomes, mesenchymal stem cells are currently the most prolific producer closely related to the occurrence and development of neurodegenerative diseases.  OBJECTIVE: To review the origin and biological characteristics of mesenchymal stem cell-derived exosomes, the isolation and identification methods of exosomes, and the progress of mesenchymal stem cell-derived exosomes in the treatment of neurodegenerative diseases.  METHODS: The literature search was performed in PubMed and CNKI databases, and the keywords were “mesenchymal stem cells; exosomes; MSC-exosomes; neurodegenerative diseases” in Chinese and English, respectively.  RESULTS AND CONCLUSION: A total of 61 eligible literatures were enrolled. Mesenchymal stem cell-derived exosomes have low immunogenicity and long-circulating half-life and can carry small molecular substances across the blood-brain barrier, which can promote nerve cell growth and neuronal differentiation. Mesenchymal stem cell-derived exosomes help damaged nervous system function and enhance vascular neurogenesis, which is becoming an emerging treatment for neurodegenerative diseases.  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 induced pluripotent stem cells in cardiovascular diseases: efficiency and safety Zeng Jianyin, Han Shen, Li Yaxiong, Liu Bin, Zhang Yayong, Jiang Lihong 2019, 23 (9):  1448-1454.  doi: 10.3969/j.issn.2095-4344.1619 Abstract ( 398 )   PDF (679KB) ( 167 )   Save BACKGROUND: Induced pluripotent stem cells are a type of reprogrammed cells with similar characteristics to embryonic stem cells, which are capable of differentiating into phenotypes associated with patient specific diseases. Moreover, their clinical application avoids ethical issues. OBJECTIVE: To review the research progress of induced pluripotent stem cells in myocardial regeneration and repair, cardiovascular disease models, drug development and screening, and drug toxicity testing. METHODS: PubMed (2006-2018) and CNKI (2013-2018) databases were retrieved for relevant articles using the keywords of “induction of pluripotent stem cells; myocardial infarction; arrhythmia; cardiovascular disease; heart failure; heart transplantation; disease model; drug toxicity” in English and Chinese, respectively. The data were reviewed one by one, and the citations involved in the literatures were also reviewed. RESULTS AND CONCLUSION: Induced pluripotent stem cells have great potential value in myocardial regeneration and repair, establishment of cardiovascular disease models, new drug development and screening, and drug toxicity detection. The application prospect of the cells is broad, but most of the research is still in the experimental stage. In addition, safety problems, such as low induction efficiency and tumorigenicity, will limit the clinical application of induced 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 Figures and Tables | References | Related Articles | Metrics

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Bone marrow mesenchymal stem cell treatment for myocardial ischemia/reperfusion injury: mechanisms of exosomes and factors Zhang Changjiang, Liang Guiyou 2019, 23 (9):  1455-1460.  doi: 10.3969/j.issn.2095-4344.1599 Abstract ( 350 )   PDF (711KB) ( 264 )   Save BACKGROUND: Myocardial ischemia/reperfusion injury is one of the most common complications in ischemic cardiomyopathy and open heart surgery. The development of bone marrow mesenchymal stem cells provides a new method for clinical prevention and treatment of myocardial ischemia/reperfusion injury.  OBJECTIVE: To review the therapeutic effect and potential mechanisms of bone marrow mesenchymal stem cells in the treatment of myocardial ischemia/reperfusion injury, in order to provide a theoretical basis for the clinical application of bone marrow mesenchymal stem cells.  METHODS: Chinese Journal Full-text Database (CNKI), WanFang, and PubMed were retrieved for articles related to the use of bone marrow mesenchymal stem cells for myocardial ischemia-reperfusion injury published from January 2000 to October 2018. The search terms were “bone marrow mesenchymal stem cells; myocardial ischaemia/reperfusion; research process” in Chinese and “bone marrow mesenchymal stem cells; myocardial ischaemia/reperfusion; cell therapy; clinical trial studies” in English. Old and repetitive viewpoints were excluded, the searched literatures were sorted out, and finally 56 articles were included for further analysis and discussion. RESULTS AND CONCLUSION: (1) In this paper, we summarize paracrine factors, exosomes miRNA and their effects in the treatment of myocardial ischemia/reperfusion injury with bone marrow mesenchymal stem cells, such as anti-inflammation, anti-apoptosis, anti-fibrosis, repair of myocardium and neovascularization. (2) We also summarize the possible molecular mechanisms of bone marrow mesenchymal stem cells involved in the treatment of myocardial ischemia/reperfusion injury, such as the role of mitochondrial fusion protein 2, regulation of myocardial autophagy, and regulation of AMPK/mTOR signaling pathway. Overall, we attempt to provide a theoretical basis for the clinical application of bone marrow mesenchymal stem cells in the treatment of myocardial ischemia/reperfusion 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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Effects of autophagy on tendinopathy Zhu Qianzheng, Gao Fuqiang, Lin Peng, Sun Wei 2019, 23 (9):  1461-1467.  doi: 10.3969/j.issn.2095-4344.1098 Abstract ( 808 )   PDF (739KB) ( 148 )   Save BACKGROUND: Tendon is a fibrous tissue that connects bone and muscle. The main function is to conduct stress from the muscles to the bone during exercise. Tendinopathy is a commonly seen disease, characterized by tendon inflammation, degeneration and injury. Autophagy is widely involved in the development of many degenerative diseases. The research method based on autophagy provides a new idea for tendon repair.  OBJECTIVE: To review the process and regulation mechanism of autophagy, and to analyze the pathological mechanism of autophagy involved in the tendinopathy so as to provide a reference for the prevention and treatment of tendinopathy.  METHODS: The articles concerning autophagy and tendinopathy were retrieved by computer in CNKI, WanFang and PubMed databases. The keywords were “autophagy, tendon, fibroblast, tendinopathy” in English and Chinese, respectively. Finally, 54 articles were obtained through systematic induction and analysis after excluding the irrelevant and repetitive articles.    RESULTS AND CONCLUSION: Autophagy can alleviate the damage to human tendon stem cells induced by oxidative stress. With the increase of the degree of extracellular matrix degradation in the tendon tissue, autophagic cell death occurs in the tendon cells due to excessive autophagy. Prostaglandin E2 significantly induces fibroblast death and autophagy in a dose-dependent manner. The muscle atrophy after the rotator cuff injury is regulated by autophagy. Rapamycin prevents peritendinous fibrosis through activation of autophagy. In conclusion, autophagy plays an important role in tendinopathy. Autophagy will become a new hotspot in tendinopathy. Further understanding of autophagy and its role in tendinopathy will contribute to finding a targeted autophagy pathway and provide new theoretical and methodological support for the intervention and treatment of tendinopathy.  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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Short- and long-term effects of olfactory ensheathing cells in the treatment of chronic spinal cord injury: a meta-analysis Chen Huijing, Chen Yun, Deng Yuer, Gan Yanling, Zhan Wengang, Tan Qijia, Xie Caijun, Li Cong, Zhang Zhiqiang 2019, 23 (9):  1468-1476.  doi: 10.3969/j.issn.2095-4344.1595 Abstract ( 292 )   PDF (883KB) ( 87 )   Save BACKGROUND: A number of clinical trials addressing olfactory ensheathing cells for the treatment of chronic spinal cord injury have been conducted in the world, but the efficacy and safety are still controversial. OBJECTIVE: To evaluate the safety and efficacy of olfactory ensheathing cell transplantation for chronic spinal cord injury, and to further compare its short- and long-term efficacy. METHODS: PubMed, Cochrane Library, EMBASE, CNKI and WanFang databases were searched at July 23, 2018 for retrieval of clinical trials addressing olfactory ensheathing cells in the treatment of chronic spinal cord injury. Types and cases of adverse events during the safety trial should be recorded in detail. In the enrolled studies, American Spinal Injury Association scale was used to assess the motor, light touch, and pinprick scores of spinal cord injury patients before and after cell transplantation. The follow-up time was recorded. Systematic evaluation of efficacy data was performed using Review Manager 5.3. RESULTS AND CONCLUSION: Both short- and long-term follow-up data showed that the neurological function of patients was significantly improved after olfactory ensheathing cell transplantation (P < 0.05), and the results were homogeneous (I2 < 50% and P > 0.1). However, the long-term efficacy was not as good as the short-term efficacy, which may be related to chronic rejection and olfactory ensheathing cell survival. The overall adverse event rate was 8.99%, and no complications associated with olfactory ensheathing cells occurred. These findings show that olfactory ensheathing cell transplantation is effective and safe in the treatment of chronic spinal cord injury, but it is still necessary to explore more minimally invasive approaches to reduce surgical complications. In addition, a large number of high-quality experiments and clinical trials are warranted to confirm factors affecting the long-term efficacy of olfactory ensheathing 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 Figures and Tables | References | Related Articles | Metrics