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08 January 2018, Volume 22 Issue 1 Previous Issue    Next Issue

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Effects of sclerostin-single chain antibody fragment on the proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells Li Shi-fei, Zhu Meng-hai, Zhang Shu-dong, Yao Qi 2018, 22 (1):  1-6.  doi: 10.3969/j.issn.2095-4344.0402 Abstract ( 369 )   PDF (2607KB) ( 273 )   Save BACKGROUND: Antagonism of bone sclerosis protein can stimulate osteogenesis and increase bone synthesis and metabolism through the Wnt/β-catenin signaling pathway. OBJECTIVE: To investigate the effects of sclerostin-single chain antibody fragment (Scl-scFv) on the proliferation and osteogenic differentiation of C57BL/6 mouse bone marrow mesenchymal stem cells (BMSCs). METHODS: BMSCs were isolated from C57BL/6 mice using whole bone marrow adherence method. Alizarin red staining was performed at the 14th day of osteogenic induction, and oil red O staining performed at the 7th day of adipogenic induction. Passage 3 BMSCs were cultured with α-MEM complete medium with (experimental) or without (control) 50 μg/L Scl-scFv aScl-scFv. Real-time PCR was used to detect type 1 collagen, alkaline phosphatase, RUNX2, osteopontin, osteocalcin at the 7th day of culture and meanwhile, alkaline phosphatase staining was done; western blot assay was used to detect expression of type 1 collagen and osteopontin proteins, and ELISA was used to detect the level of osteocalcin in the cell supernatant at 4, 7, 10 days of culture. RESULTS AND CONCLUSION: Formation of calcium nodules and orangered oil droplets was obviously visible in the BMSCs after osteogenic and adipogenic induction, respectively. Over time, the absorbance value showed no difference between the experimental and control group. Compared with the control group, the experimental group showed significant increases in mRNA and protein expression of type 1 collagen and osteopontin as well as in protein expression of alkaline phosphatase, RUNX2 and osteocalcin (P < 0.05). Moreover, stronger alkaline phosphatase staining was found in the experimental group relative to the control group. These findings indicate that Scl-scFv has no effect on BMSCs proliferation, but can promote the osteogenic capacity of BMSCs in vitro. 中国组织工程研究杂志出版内容重点：干细胞；骨髓干细胞；造血干细胞；脂肪干细胞；肿瘤干细胞；胚胎干细胞；脐带脐血干细胞；干细胞诱导；干细胞分化；组织工程 Figures and Tables | References | Related Articles | Metrics

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Effect of poly(hydroxybutyrate-co-hydroxyoctanoate)/collagen composite osteochondral scaffold combined with bone marrow mesenchymal stem cells in the repair of articular osteochondral defects Jian Xiao-dong, Zhang Yong-hong, Zhang Yu, Liu Lai-you 2018, 22 (1):  7-12.  doi: 10.3969/j.issn.2095-4344.0403 Abstract ( 292 )   PDF (1288KB) ( 248 )   Save BACKGROUND: Preliminary experiments have confirmed that poly(hydroxybutyrate-co-hydroxyoctanoate) (PHBHOx)/collagen composite osteochondral scaffold exhibits desirable pore structure and biocompatibility. OBJECTIVE: To investigate the effect of PHBHOx/collagen composite osteochondral scaffold carrying bone marrow mesenchymal stem cells in the repair of articular osteochondral defects in the weight-bearing area of rabbits. METHODS: Cone-shaped osteochondral defects were created in the femoral medial condyle of the right knee of 30 New Zealand white rabbits. Then, the rabbit models were randomized into three groups and underwent implantation of PHBHOx/collagen composite osteochondral scaffold carrying bone marrow mesenchymal stem cells in the scaffold-cell group, PHBHOx/collagen composite osteochondral scaffold in the scaffold group and no intervention in the control group. At 4 and 12 weeks after surgery, animals were sacrificed for gross, Micro-CT, histological and immunohistochemical collagen II observations. RESULTS AND CONCLUSION: At 12 weeks after surgery, Micro-CT scanning results suggested that osteochondral defects were not repaired in the control group, repaired incompletely in the scaffold group with many new bone trabeculae, and repaired completely in the scaffold-cell group. Histological results showed that at 4 weeks after surgery, the defects in the control group were filled with amorphous tissues, subchondral bone formation just occurred in the scaffold group but increased in the scaffold-cell group. At 12 weeks after surgery, trabecular bone structure with no cartilage lacuna was observed in the control group; incomplete subchondral bone formation was observed in the scaffold group, and the cartilage layer was repaired by the fibrous tissues; in the scaffold-cell group, osteochondral defect repair was complete, with the emergence of tidal line, and the newborn cartilage was completely integrated with the surrounding normal tissue in addition to a similar thickness. At 12 weeks after surgery, collagen II basically did not express in the control group, weakly expressed in the scaffold group and highly expressed in the scaffold-cell group. In short, the PHBHOx/collagen composite osteochondral scaffold promotes the repair of articular osteochondral defects in the weight-bearing area.  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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Titanium surface modification by acidic oxidation treatment activates the Wnt signaling pathway in bone marrow mesenchymal stem cells Wang Wei, Du Yuan-hong 2018, 22 (1):  13-19.  doi: 10.3969/j.issn.2095-4344.0404 Abstract ( 349 )   PDF (4833KB) ( 180 )   Save BACKGROUND: Preliminary findings have shown that titanium dioxide nanotube array prepared on the titanium surface by an anodizing method can significantly affect the osteoblast differentiation. OBJECTIVE: To observe the effect of titanium surface modification by acidic oxidation treatment on the Wnt signaling pathway in bone marrow mesenchymal stem cells. METHODS: The micro/nano-structure composed of nanotubes was prepared by acidic oxidation method. The oxidizing voltage was set to 5 V and 20 V. The polished pure titanium was used as control. Primary cultured Sprague-Dawley rat bone marrow mesenchymal stem cells were seeded onto the titanium surface of the three groups. After 3 and 7 days of incubation, real-time quantitative PCR was used to detect the genes levels of canonical Wnt and non-canonical Wnt signaling pathway and western blot method was used to detect β-catenin expression level in the nuclei, respectively. RESULTS AND CONCLUSION: (1) Canonical Wnt signaling expression: Wnt1 and Wnt3a expression on the micro/nano-structure surfaces significantly increased compared to the control surface (P < 0.05). (2) Non-canonical Wnt signaling expression: compared with the control surface, Wnt4 expression decreased on the two kinds of micro/nano structure surfaces (P < 0.05); Wnt7a decreased on the small-diameter nanotube (R5) surface (P < 0.05), increased on the big-diameter nanotube surface (R20) (P < 0.05); Wnt11 elevated on both two micro/nano structure surfaces (P < 0.05). Wnt5a expression level had no obvious change in the three groups. (3) β-catenin expression level in the nuclei significantly increased after titanium surface modification by different acidic oxidation treatments compared to the control surface. These results show that the micro/nano-structure titanium surface activates the canonical Wnt signaling pathway in the bone marrow mesenchymal 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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Umbilical cord mesenchymal stem cell conditioned medium combined with hyaluronic acid for mouse skin repair Lou Min-ming, Wang Hong-wei, Ma Jie 2018, 22 (1):  20-25.  doi: 10.3969/j.issn.2095-4344.0405 Abstract ( 381 )   PDF (6737KB) ( 263 )   Save BACKGROUND: Numerous studies have shown that mesenchymal stem cells (MSCs) can effectively promote tissue repair by secreting various bioactive factors. OBJECTIVE: To observe the effects of umbilical cord cord mesenchymal stem cells conditioned media (UCMSCs-CM) combined with hyaluronic acid (HA) on the repair of skin wounds in mice. METHODS: The UCMSCs-CM was collected, and added with HA to prepare the gel solution. Forty mice were selected to prepare animal models of full-thickness skin wound. According to different treatments, the mice were randomly divided into four groups, blank control group (0.5 mL of normal saline), UCMSCs-CM group (0.5 mL of UCMSCs-CM), HA group (0.5 mL of HA), UCMSCs-CM+HA group (0.5 mL of UCMSCs-CM+0.5 mL of HA). Each mouse received three treatments a day (in the morning, at noon and at night), for continuous 7 days. The wound size was measured and the wound healing rate was calculated. The factors related to skin repair were detected by immunohistochemstry and qRT-PCR methods. RESULTS AND CONCLUSION: After treatment, the wound size was reduced to different extents in the treatment groups as compared with the blank control group. The UCMSCs-CM combined with HA significantly improved the wound healing rate as compared with the other groups (P < 0.01). Strongly positive expression of the factors related in skin injury, such as vascular endothelial growth factor and matrix metalloproteinase 9 protein, were found in the UCMSCs-CM+HA group; moreover, the mRNA levels of basic fibroblast growth factor, transforming growth factor β and matrix metalloproteinase 9 protein were significantly higher in the UCMSCs-CM+HA group than the blank control group (P < 0.01). To conclude, UCMSCs-CM combined with HA can accelerate skin wound repair in mice, and exhibit better effects than the UCMSCs-CM or HA alone, which provides theoretical support for stem cells combined with biological scaffolds in skin wound repair. Figures and Tables | References | Related Articles | Metrics

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GW4869 inhibits the release of exosomes from bone marrow mesenchymal stem cells Sun Shu-li, Xiao Pei-xin, Ding Hui, Wang Jing, Liu Zi-quan, Liu Jin-yang, Wang Xue, Shi Sha, Lv Qi, Fan Hao-jun 2018, 22 (1):  26-31.  doi: 10.3969/j.issn.2095-4344.0407 Abstract ( 879 )   PDF (4502KB) ( 285 )   Save BACKGROUND: Bone marrow mesenchymal stem cells (BMSCs) and BMSCs-derived exosomes have similar functions, but the regulatory mechanism underlying the release of exosomes is still unclear. OBJECTIVE: To investigate the role of GW4869, an inhibition of neutral sphingomyelinase 2, in the release of exosomes in BMSCs and the influence of GW4869 on BMSCs proliferation. METHODS: Rat BMSCs were divided into three groups: normal control group, 24-hour GW4869 treatment group and withdrawal of GW4869 for 24 hours group (24-hour GW4869 treatment followed by 24-hour successive culture with drug withdrawal). Cultured cells were collected to extract exosomes by ultracentrifugation. Western blot was used to detect exosome-associated proteins CD63 and tumor susceptibility gene 101 (TSG101). The concentration and size distribution of exosomes were measured using nanoparticle tracking analysis. BCA was used to test the level of total proteins in exosomes. Live cell imaging system was used to observe the influence of GW4869 on BMSCs proliferation. RESULTS AND CONCLUSION: (1) Western blot results showed that exosomes expressed marker proteins such as CD63, TSG101. (2) Findings from the nanoparticle tracking analysis confirmed that the size of released exosomes was about 114 nm. (3) Significantly reduced release of exosomes was found in the two treatment groups compared with the normal control group (P < 0.01), but there was no significant difference between 24-hour GW4869 treatment group and withdrawal of GW4869 for 24 hours group (P > 0.05). (4) No significant difference in the proliferation of BMSCs was found among the three groups (P > 0.05). To conclude, 24-hour W4869 can inhibit the release of exosomes by BMSCs and this inhibitory effect is still sustained within 24 hours after drug withdrawal. However, GW4869 has no influence on the proliferation of 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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Overexpression of stromal cell-derived factor-1 promotes the proliferation and migration of bone marrow mesenchymal stem cells in vitro Chen Shao-qiang, Wu Bi-lian, Wang Shan-shan, Huang Hai-hui 2018, 22 (1):  32-39.  doi: 10.3969/j.issn.2095-4344.0408 Abstract ( 342 )   PDF (6478KB) ( 209 )   Save BACKGROUND: The stromal cell-derived factor-1 (SDF-1)/C-X-C chemokine receptor type 4 (CXCR4) signaling pathway cannot only improve the migration ability of bone marrow mesenchymal stem cells (BMSCs), but also restrain BMSCs apoptosis, increase BMSCs survival and improve the proliferation activity of BMSCs. OBJECTIVE: To construct a rat BMSCs line with SDF-1α overexpression and to explore its influence on the proliferation and migration of BMSCs in vitro. METHODS: The SDF-1α overexpression vector (pNL-SDF-1α-IRES2-EGFP) was constructed. The lentivirus particles were packaged by transferring pNL-SDF-1α-IRES2-EGFP, pNL-IRES2-EGFP and GV-118-SDF-1α-siRNA into 293T cells. The BMSCs lines with SDF-1α overexpression in SDF-1α-BMSCs group, null-BMSCs group and siRNA-BMSCs group were established by transfecting SDF-1α-lentiviru, null-lentivirus and siRNA-lentivirus into BMSCs respectively. The expression of SDF-1α at mRNA and protein levels in BMSCs was evaluated by RT-PCR and western blot assay, respectively. The influence of SDF-1α on proliferation and migration of BMSCs were evaluated by MTT and Transwell migration experiment respectively.  RESULTS AND CONCLUSION: The pNL-SDF-1α-IRES2-EGFP recombinant plasmid was successfully constructed, which was proved by sequencing results. EGFP was strongly expressed in 293T cells and BMSCs in all groups after 48 hours in lentivirus transfection. SDF-1α at mRNA and protein levels were highly expressed in the SDF-1α-BMSCs group, but the expression was significantly inhibited in the siRNA-BMSCs group. The proliferative ability of BMSCs was strengthened in the SDF-1α-BMSCs group, and SDF-1α was found to significantly promote the transmembrane migration of BMSCs. The migration index of BMSCs incubated with anti-SDF-1α multi-antibodies was restrained markedly. To conclude, the lentivirus vector cannot only infect BMSCs efficiently but also make SDF-1 expresse stably in BMSCs. The overexpression of SDF-1α can improve the proliferation and migration abilities of 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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Role of mature liver cells and oval cells in liver regeneration after liver injury Wang Ya-ping, Kong Xiang-ping, Zhuo Li, Tang Xiao-ping, Gao Hong-bo, Tong Ming-hua 2018, 22 (1):  40-45.  doi: 10.3969/j.issn.2095-4344.0401 Abstract ( 466 )   PDF (4548KB) ( 294 )   Save BACKGROUND: Retrorsine (RS) is a chemical agent for the long-term inhibition of mature liver cell division and proliferation. OBJECTIVE: To establish a rat model of liver injury by combined use of RS and 1/3 partial hepatectomy, to observe the proliferation of liver cells and oval cells in rats after liver injury, and to discuss the relationship between liver regeneration and mature liver cells and oval cells after liver injury.  METHODS: Thirty male Sprague-Dawely rats were randomized into two groups (n=15 per group): RS group and control group. Rats in the RS group were subjected to intraperitoneal injection of RS, 30 mg/kg, twice in total, with 2 weeks in between; and rats in the control group were injected physiological saline instead of RS. Four weeks after the last injection, the 1/3 partial hepatectomy was performed in two groups of rats. Liver pathological and morphological changes as well as cell proliferation were observed, and CK19 and C-kit immunohistochemical detections of the rat liver in the two groups were conducted at different time points after operation. RESULTS AND CONCLUSION: At 20 days after operation, the body mass of the RS group rats was still lower than the baseline, and the liver increase was obviously less than that in the control group; there was cell body swelling shown by hematoxylin-eosin staining, loose cytoplasm, extensive vacuoles degeneration of liver cells, and clustered or scattered oval cells around the portal area of small bile duct and in the hepatic lobule. However, in the control group, the body mass was close to the baseline, liver damage was lighter than that in the RS group, a large number of mature liver cells proliferated under BrdU Immunofluorescence at 20 days after operation; liver oval cells proliferated and distributed in the liver cell line at 14 days after operation, with morphology and immunohistochemical markers consistent with oval cells in the RS group. These findings indicate that the rat model of acute liver injury is successfully established by combining retrorsine with 1/3 partial hepatectomy, liver poisoning and the proliferation of liver stem cells and mature liver cells after poisoning can be seen in the experiment, which firmly confirm that liver cell renewal and regeneration after injury is accredited to the combined action of liver stem cells in liver basin and mature liver 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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Promoting angiogenesis by con-transplantation of bone marrow mesenchymal stem cells and human umbilical vein endothelial cells transfected with vascular endothelial growth factor 165 gene Xian De-bin, Ming Hua-wei, Xu Rong-sheng, Xia De-lin 2018, 22 (1):  46-52.  doi: 10.3969/j.issn.2095-4344.0409 Abstract ( 385 )   PDF (6590KB) ( 215 )   Save BACKGROUND: How to promote the early vascularization of large tissue-engineered bone has become the hotspot of current research. Cell co-culture and the addition of bioactive factors to promote angiogenesis are very good methods to promote early vascularization. OBJECTIVE: To explore the ability of angiogenesis by co-transplantation of bone marrow mesenchymal stem cells (BMSCs) and human umbilical vein endothelial cells (HUVECs) which were transfected with vascular endothelial growth factor 165 (VEGF165) gene in vivo, to move forward a single step to offer theoretical basis and experimental basis to build vascularized tissue-engineered bone which can be used to repair large segmental bone defects. METHODS: We built an ischemic skin flap with 4 cm×1.5 cm in the back of Sprague-Dawley rats, and then BMSCs+VEGF165-transfected HUVECs (group A), VEGF165-transfected HUVECs (group B), BMSCs+non-transfected HUVECs (group C), non-transfected HUVECs (group D), DMEM (group E) were respectively transplanted. ELISA method was used to detect peripheral blood VEGF level. Histologically, survival and microvessel density of the flap were observed. RESULTS AND CONCLUSION: (1) The flap survival quality of group A was better than that in the other groups. VEGF exhibited high expression continuously high expression at 2, 4, 7, 14 days after transplantation, and reached the peak at 7 days, but the expression level at 14 days was obviously lower than that at 2 days postoperatively. The VEGF level of group always exceeded that in group B at different time points (P < 0.05). The flap survival rate and microvessel density of group A was significantly higher than that in the other groups at 11 days postoperatively (both P < 0.05). In summary, co-transplantation of BMSCs and VEGF165-transfected HUVECs can promote survival of an ischemic flap in vivo through pro-angiogenic actions. 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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Intramuscular injection of estradiol combined with bone marrow mesenchymal stem cell transplantation for spinal cord injury Bu Zhi-yong, Hu Liang-jiao, Li Chen, Li An-jun 2018, 22 (1):  53-58.  doi: 10.3969/j.issn.2095-4344.0410 Abstract ( 256 )   PDF (4756KB) ( 181 )   Save BACKGROUND: Even though estrogen can prevent secondary spinal cord injury, exert a neuroprotective role, and inhibit apoptosis in mesenchymal stem cells in vitro, little is reported on the combined use of estrogen and bone marrow mesenchymal stem cells (BMSCs) in the treatment of spinal cord injury. OBJECTIVE: To investigate the effects and mechanism of s intramuscular injection of estradiol combined with BMSCs in the treatment of spinal cord injury. METHODS: One hundred and forty-four Sprague-Dawley rats were randomly divided into four groups: combined group, BMSCs group, estradiol group and control group. After the establishment of spinal cord injury model, the rats were given intramuscular injection of estradiol 250 µg/kg estradiol combined with 6×106 BMSCs (60 μL), BMSCs, estradiol or PBS in different groups, respectively. After transplantation, related indicators were detected. RESULTS AND CONCLUSION: At 1 and 4 weeks after modeling, the behavioral scores in the combined group were significantly higher than those in the other three groups (P < 0.05). At 3 and 7 days after transplantation, superoxide dismutase levels in the combined group were significantly higher than those in the other three groups, but the malondialdehyde levels were lowest in the combined group (P < 0.05). At 3 and 7 days after transplantation, the apoptotic rate in the spinal cord tissues was significantly lower in the combined group than the other three groups (P < 0.05). To conclude, estradiol can alleviate secondary cell apoptosis and inhibit oxidative stress after spinal cord injury, which contributes to the spinal motor function recovery after BMSCs transplantation. Figures and Tables | References | Related Articles | Metrics

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Therapeutic effect of bone marrow mesenchymal stem cell transplantation for spinal cord injury Sun Jing-song, Zhou Xue-ying, Qu Shu-xian, Li Shuang-yue 2018, 22 (1):  59-64.  doi: 10.3969/j.issn.2095-4344.0411 Abstract ( 362 )   PDF (5284KB) ( 205 )   Save BACKGROUND: At present, treatments for spinal cord injury are limited, with poor outcomes. Therefore, it is of great importance to explore new treatment methods. OBJECTIVE: To observe the therapeutic effect of bone marrow mesenchymal stem cells (BMSCs) injection via the caudal vein on spinal cord injury in rats. METHODS: BMSCs were isolated and cultured in vitro by whole bone marrow adherence method. The surface markers were identified by flow cytometry. Thirty Sprague-Dawley rats were randomly divided into control group, spinal cord injury group and BMSCs transplantation group, 10 rats in each group. A rat spinal cord injury model was established by occlusion of the 10th thoracic vertebra using an aneurysm clamp, and 2×106 BMSCs were injected through the caudal vein at 10 minutes after modeling. Basso-Bettle-Bresnahan (BBB) score for motor function recovery was assessed at 0, 10, 20, 30 days after transplantation. The therapeutic effect was evaluated by hematoxylin-eosin staining and electron transmission microscopy at 30 days after implantation. RESULTS AND CONCLUSION: Under the microscope, fusiformis-shaped or fibroblast-like cells were observed. The expression rate of CD44 and CD90 was more than 90% and the expression of CD45 was less than 2%, by which, the BMSCs were identified. The BBB scores were significantly higher in the BMSCs transplantation group than the spinal cord injury group at 20 and 30 days after transplantation (P < 0.05). Hematoxylin-eosin staining showed that there was spinal cord tissue damage, vascular rupture injury, neuronal cell degeneration and inflammatory cell infiltration in the spinal cord injury group. After BMSCs transplantation, the number of spinal cord neurons was markedly increased with intact cytomembrane and clear nucleolus. Electron microscopic results showed that spinal cord axon swelling, demyelination, nerve axon deformation and necrosis were observed in the spinal cord injury group, while after BMSCs transplantation, the rat spinal cord axon structure was repaired, and partially lost myelin was recovered with uniform thickness. To conclude, BMSCs transplantation via the caudal vein has a significant therapeutic effect on spinal cord injury in rats by repairing the spinal cord structure and protecting the integrity of axon and myelin structures. 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 placenta-derived mesenchymal stem cell transplantation provides neuroprotection against cerebral infarction in rats Chen Dong-ping, Hou Shu-hong, Guo Yuan, Hu Zhi-zhou, Hu Xiao-hong, Chen Yan-gui, Chen Ming-sheng 2018, 22 (1):  65-69.  doi: 10.3969/j.issn.2095-4344.0412 Abstract ( 281 )   PDF (4119KB) ( 213 )   Save BACKGROUND: Bone marrow mesenchymal stem cells improve neurological functional recovery from cerebral infarction, but they are a rare population in the bone marrow with difficulty in cell separation and purification. OBJECTIVE: To investigate the neuroprotective effects and the potential mechanisms of human placenta-derived mesenchymal stem cell transplantation for cerebral infarction in rats. METHODS: Totally 120 rats subjected to middle cerebral artery occlusion were randomized into treatment group and control (n=60 per group). The rats were intravenously treated with human placenta-derived mesenchymal stem cells in the treatment group or the phosphate buffer saline in the control group. Then, a modified neurological severity score was assessed at 1, 3, 7, 14 days post transplantation, and measurement of infarct volume in the ischemic brain was performed using 2,3,5-triphenyltetrazolium chloride staining at 14 days post transplantation. The anti-human specific immunostain for mitochondria in the ischemic brain was performed and the mitochondria-positive cells were counted; TUNEL immunostaining was performed and TUNEL positive cells were counted. ELISA assays for brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) were also performed in the ischemic brain. RESULTS AND CONCLUSION: At 1, 3, 7 and 14 days after treatment, the modified neurological severity score in the treatment group was significantly lower than that in the control group (P < 0.05). At 14 days after treatment, the infarct volume in the treatment group was significantly lower than that in the control group (P < 0.05), only few mitochondria-positive cells were present in the ischemic brain, and the number of TUNEL positive cells in the treatment group was significantly less than that in the control group (P < 0.05). At 3 and 14 days after treatment, BDNF expression levels in the treatment group were significantly higher than those in the control group (P < 0.05). At 7 and 14 days after treatment, VEGF expression levels in the treatment group were significantly higher than those in the control (P < 0.05). At 7 days after treatment, HGF expression level in the treatment group was significantly higher than that in the control group (P < 0.05). To conclude, intravenous administration of human placenta-derived mesenchymal stem cells can promote neuroprotective effects against cerebral infarction. These effects may be related to the increase of BDNF, VEGF and HGF expression and the decrease of apoptosis in the ischemic brain. 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 cells versus bone marrow mononuclear cells for treating cerebral palsy Dai Guang-hui, Liu Xue-bin, Zhang Zan, Cheng Hong-bin, Wang Xiao-dong, An Yi-hua 2018, 22 (1):  70-76.  doi: 10.3969/j.issn.2095-4344.0413 Abstract ( 395 )   PDF (1185KB) ( 169 )   Save BACKGROUND: Bone marrow mesenchymal stem cells (BMSCs) and bone marrow mononuclear cells(BMMNCs) have been both used to treat spastic cerebral palsy. However, the differences in their therapeutic effects remain unknown. OBJECTIVE: To compare the therapeutic effects of BMMSCs and BMMNCs in cerebral palsy children as well as on fine motor function. METHODS: 105 children with spastic cerebral palsy were enrolled and randomly assigned to three groups: BMMSCs group, BMMNCs group and control group. Patients in the two transplantation groups received four intrathecal cell injections, and those in the control group received Bobath therapy, twice a day, for consecutive 3 weeks. The Gross Motor Function Measure (GMFM) and Fine Motor Function Measure (FMFM) were used to evaluate the therapeutic efficacy at 3, 6 and 12 months after transplantation. RESULTS AND CONCLUSION: At 3 months after cell transplantation, scores in A dimension of GMFM and in A, C dimensions of FMFM in BMMSC group were all superior to those of BMMNC group and control group (P < 0.05). At 6 months after cell transplantation, scores in A, B dimensions of GMFM and in A, B, C, D and E dimensions of FMFM in BMMSC group were better than those of BMMNC group and control group (P < 0.05), and total scores of GMFM and FMFM were also better in the BMMSC group (P < 0.05). At 12 months after cell transplantation, scores in A, B and C dimensions of GMFM and A, B, C, D and E dimensions of FMFM scores in BMMSC group were all superior to those of BMMNC group and control group (P < 0.05) as well as the total GMFM and FMFM scores. There were six cases of low intracranial pressure headache in BMMNC group and six cases of low-grade fever in BMMSC group. In summary, both BMMSCs transplantation and BMMNCs transplantation are safe, effective and feasible for the treatment of spastic cerebral palsy in children, and moreover, BMMSCs transplantation is a better method than BMMNCs transplantation to improve gross and fine motor functions of spastic cerebral palsy children. 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 adiponectin gene-modified human amniotic membrane mesenchymal stem cell transplantation on islet neogenesis in diabetic rats Li Feng-min, Gu Ling-ling 2018, 22 (1):  77-82.  doi: 10.3969/j.issn.2095-4344.0414 Abstract ( 319 )   PDF (1224KB) ( 144 )   Save BACKGROUND: Adiponectin is the only lipid-derived cytokine that exerts a protective effect on the human body, and it also plays an important role in the development and progression of diabetes mellitus. OBJECTIVE: To explore the effect of adiponectin gene-modified human amniotic membrane mesenchymal stem cell (hAMSCs) transplantation on islet neogenesis and the relevant mechanism.  METHODS: Fifteen Sprague-Dawley rats without any processing were randomly selected from 98 Sprague-Dawley rats as control group. The remaining rats were used to establish diabetic models by intraperitoneal injection of 60 mg/kg streptozotocin, and the animal model was successfully prepared in 75 rats. Then, the model rats were randomized into diabetic, hAMSCs, adiponectin-modified hAMSCs groups, followed by 3-day caudal vein injection of normal saline (20 μL), 2×106/L hAMSCs suspension (20 μL), and adiponectin-modified hAMSCs suspension (20 μL), respectively. Blood glucose and serum insulin levels of all rats were detected at 7, 14, 21, 28 days after transplantation. RT-PCR and western blot were used to test mRNA and protein expression of adiponectin, Caspase3 and Bax, respectively at 21 days after transplantation. Pathological changes of the rat pancreatic tissues were observed by hematoxylin-eosin staining. Apoptosis of islet cells was observed using TUNEL method.  RESULTS AND CONCLUSION: (1) Compared with the control group, the blood glucose level was obviously increased, while the serum insulin level was significantly decreased in the diabetic group (P < 0.05). Compared with the diabetic group, the blood glucose level was obviously decreased, while the serum insulin level was significantly increased in the hAMSCs group (P < 0.05). Compared with the hAMSCs group, the blood glucose level was further decreased, while the serum insulin level was further increased in the adiponectin-modified hAMSCs group (P < 0.05). (2) The expression of adiponectin at mRNA and protein levels was significantly higher in the adiponectin-modified hAMSCs group than the other groups (P < 0.05). (3) Compared with the diabetic group, the expression of Caspase-3 and Bax at mRNA and protein levels was significantly decreased in the adiponectin-modified hAMSCs group (P < 0.01) and in the hAMSCs group (P < 0.05). (4) In the adiponectin-modified hAMSCs group, the morphology of the islet was dramatically recovered and the number of islet cells was minimally reduced. To conclude, the adiponectin-modified hAMSCs transplantation can improve the blood glucose level and promote islet neogenesis in diabetic rats, probably by regulating the expression of Caspase-3 and Bax in the islet and reducing apoptosis in islet 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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Treatment for nephrotic syndrome: vascular endothelial growth factor gene modified amniotic mesenchymal stem cells transplantation Gao Da-wei, Yang Peng 2018, 22 (1):  83-88.  doi: 10.3969/j.issn.2095-4344.0415 Abstract ( 348 )   PDF (1307KB) ( 163 )   Save BACKGROUND: The expression of exogenous genes in mesenchymal stem cells is beneficial to enhance the transplantation effect and improve the differentiation rate. OBJECTIVE: To verify whether the transplantation of amniotic mesenchymal stem cells (AMSCs) can improve the renal function and blood coagulation in rats with nephrotic syndrome by means of vascular endothelial growth factor (VEGF) modification. METHODS: The 18 of 72 male Sprague-Dawley rats were assigned to normal group (without any treatment), and the other 54 rats were intravenously injected with doxorubicin to establish adriamycin nephropathy rat models which were randomly divided into three groups: model group (tail vein injection of 10 μL of 0.9% PBS injection), AMSCs group (tail vein injection of 10 Μl of AMSCs suspension), VEGF modified group (tail vein injection of 10 μL of VEGF modified AMSCs suspension). The injection in each group began at 24 hours after modeling, once a day for 3 consecutive days. The levels of total cholesterol (TC), triglyceride (TG), total protein (TP), albumin (Alb), high density lipoprotein (HDL), low density lipoprotein (LDL), creatinine (Cr), blood urea nitrogen (BUN) and coagulation index were measured by an automatic biochemical analyzer. The 24-hour urinary protein was determined by trichloroacetic acid method. The mRNA and protein expression of heparanase (HPA) and VEGF in renal tissue were detected by RT-PCR and western blot, respectively. RESULTS AND CONCLUSION: (1) Compared with the normal group, the contents of 24-hour urinary protein, TC, TG, LDL, Cr, BUN in the model group were significantly increased (P < 0.05), while the contents of TP, Alb, HDL were significantly decreased (P < 0.01). The serum levels of TC, TG, LDL, Cr, BUN in the AMSCs group and VEGF-modified group were significantly lower than those in the model group (P < 0.05), while TP, Alb and HDL were significantly higher in the model group (P < 0.05). Compared with the AMSCs group, these indexes were significantly improved in the VEGF-modified group (P < 0.05). (2) The coagulation indexes of the model group showed a tendency of hypercoagulability. Compared with the model group, the hypercoagulability in the AMSCs and the VEGF-modified group were improved, especially in the VEGF-modified group. (3) The expression of HPA gene and protein in the model group was significantly higher than that in the normal group. The expression of HPA gene and protein in the AMSCs group and VEGF-modified group was lower than that in the model group. The expression of HPA gene and protein in the VEGF modified group was the lowest, while the expression of VEGF gene and protein in the VEGF modified group was the highest among the groups (P < 0.05), and there were significant differences between groups (P < 0.05). To conclude, VEGF gene-modified AMSCs can be transplanted via tail vein to improve renal function and hypercoagulable state in rats with nephrotic syndrome. 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 granulocyte-colony stimulating factor on regulatory T cells and related cytokines after allogeneic hematopoietic stem cell transplantation Xiang Jin-feng 2018, 22 (1):  89-94.  doi: 10.3969/j.issn.2095-4344.0416 Abstract ( 455 )   PDF (1123KB) ( 140 )   Save BACKGROUND: Acute graft-versus-host disease (aGVHD) is an inflammatory disease mediated by regulatory T cells. It is of certain significance to prevent and treat aGVHD by improving the levels of CD4+CD5+ regulatory T cells (CD4+CD5+Treg)and related inflammatory factors in the body. OBJECTIVE: To investigate the effect of granulocyte colony stimulating factor (G-CSF) on CD4+CD5+ regulatory T cells (CD4+CD5+Treg) and cytokines in children with hematological malignancies after allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: Seventy children with hematological malignancies undergoing allo-HSCT were enrolled. G-CSF was mobilized in the 45 cases (G-CSF group) before allo-HSCT transplantation. The other 25 cases were assigned to non-G-CSF group. Peripheral blood samples were collected at 4 weeks after allo-HSCT. Another 60 healthy children were selected as control group. The levels of T cells, serum interleukin-35 (IL-35) and interferon-γ (INF-γ) were measured by flow cytometry and ELISA, respectively. According to whether aGVHD occurred after allo-HSCT, the 70 cases were divided into aGVHD positive group and aGVHD negative group. The relationship between the changes of T cells and cytokines with aGVHD was analyzed.  RESULTS AND CONCLUSION: (1) The percentage of CD4+CD5+Treg in CD4+ T and CD4+FoxP3+ T cells as well as serum IL-35 level in children with hematological diseases were lower than those in the control group (P < 0.05), while the levels of INF-γ were significantly higher than that in the control group (P < 0.05). (2) The percentage of CD4+CD5+Treg in CD4+ T cells and CD4+FoxP3+ T cells as well as serum IL-35 level in the G-CSF group were lower than those in the non-G-CSF group (P < 0.05), while the levels of INF-γ was higher than that in the non-G-CSF group (P < 0.05). (3) There were 7 cases (16%) of aGVHD in the G-CSF group and 10 cases (40%) of aGVHD in the non-G-CSF group at 4 weeks after allo-HSCT, and the incidence of aGVHD was significantly different between the G-CSF and non-G-CSF groups (P=0.022). (4) The percentage of CD4+CD5+Treg in CD4+ T and CD4+FoxP3+ T cells as well as serum IL-35 level in the aGVHD negative group were higher than those in the aGVHD positive group (P < 0.05), while the levels of INF-γ were significantly lower than that in the aGVHD positive group (P < 0.05). (5) CD4+CD5+Treg and CD4+FoxP3+ T cells were positively correlated with the IL-35 level, but negatively correlated with the INF-γ level by Pearson single factor analysis. To conclude, G-CSF mobilization can significantly improve CD4+CD5+Treg cells and its transcription factor Foxp3 after allo-HSCT, which may be useful for improving the therapeutic effect of allo-HSCT and preventing aGVHD in patients with malignant hematological 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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Isolation, culture and biological characteristics of human urine-derived stem cells Zhao Chang-hui, Hamulati•Tusong, Mulati•Rexiati, Wang Feng, Ma Jun, Anniwaer•Yasheng 2018, 22 (1):  95-100.  doi: 10.3969/j.issn.2095-4344.0417 Abstract ( 511 )   PDF (4057KB) ( 168 )   Save BACKGROUND: As an emerging stem cell family, urine-derived stem cells have attracted more and more attentions in the tissue engineering construction. OBJECTIVE: To study the culture method of urine-derived stem cells, and to identify the biological characteristics of urine-derived stem cells. METHODS: Cleaning urine samples were harvested and centrifuged, and urine-derived stem cells were isolated from the urine samples and extensively expanded in vitro. Cell growth curve was measured by MTT method, and cell surface markers were detected by flow cytometry. Meanwhile, the cells were subjected to osteogenic and adipogenic induction. RESULTS AND CONCLUSION: Urine-derived stem cells were successfully isolated from the urine samples, which grew and proliferated rapidly. After subculture, the cells exhibited an S-shaped growth. The isolated urine-derived stem cells expressed CD29, CD44, CD73 and CD90, indicating that the cells maintained the activity  of stem cells. Moreover, the isolated cells had the ability of osteogenic and adipogenic differentiation. To conclude, urine-derived stem cells have strong proliferation and differentiation potentials, as a kind of economic, convenient, non-invasive source of cells, which can provide great convenience for urethral defect repair and organ reconstruction. 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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Negative pressure promotes epidermal differentiation of bone marrow mesenchymal stem cells Zhao Bo-wen, Xu Qiang, Ge Quan-hu, Li Bo-long, Peng Xin-yu, Zhang Hong-wei, Wu Xiang-wei 2018, 22 (1):  101-106.  doi: 10.3969/j.issn.2095-4344.0418 Abstract ( 369 )   PDF (4999KB) ( 152 )   Save BACKGROUND: As a physical factor, negative pressure can promote the osteogenic differentiation and endothelial differentiation of mesenchymal stem cells. If a negative pressure exerts effects on the epidermal differentiation of mesenchymal stem cells, it will be highly important for the combination use of negative pressure and mesenchymal stem cells in wound healing. OBJECTIVE: To explore the effect of negative pressure on the epidermal differentiation of bone marrow mesenchymal stem cells. METHODS: Bone marrow mesenchymal stem cells of New Zealand white rabbits were isolated and cultured. Then, the passage 3 cells were induced for epidermal differentiation under negative pressure (-16.625 kPA, twice a day, once for 4 hours) as experimental group. Another cells induced under no negative pressure were used as control group. After induction, cell growth curve was drawn in each group, and the expression of cytokeratin 5 and cytokeratin 10 mRNA was examined by real-time PCR at 2 weeks after induction. RESULTS AND CONCLUSION: The cell growth of the experimental group was inhibited, and the mRNA expression of cytokeratin 5 and cytokeratin 10 was significantly increased compared with the control group (P < 0.05). These findings indicate that under the condition of negative pressures, the epidermal differentiation ability of bone marrow mesenchymal stem cells is increased, and in contrary, the cell proliferation is inhibited. 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 formyl peptide receptor on the differentiation of neural stem/progenitor cells into neurons Zhang Liang, Cheng Hui, Leng Ming-hao, Pan Jian-hai, He Xiang-chun, Zhang Yi-ming, Lu Shan, Chen Hua 2018, 22 (1):  107-112.  doi: 10.3969/j.issn.2095-4344.0419 Abstract ( 320 )   PDF (4017KB) ( 205 )   Save BACKGROUND: Previous studies have observed the expression of formyl peptide receptors (FPRs) in neural stem/progenitor cells (NSPCs) and confirmed that FPRs can promote the migration of NSPCs and induce them to differentiate into neurons. FPRs ligands are present in damaged tissues, but the binding of different ligands with FPRs may lead to different and even opposite biological effects. OBJECTIVE: To investigate the effect on the differentiation of NSPCs into neurons after the binding of the ligands produced following spinal cord injury with FPRs. METHODS: Immunofluorescence staining, western blot and flow cytometry were used to analyze the expression of FPRs in NSPCs. Immunofluorescent staining with confocal microscope detection was used to analyze the effect of homogenates of the spinal cord on the differentiation of FPR1+ or FPR2+ NSPCs into neurons. RESULTS AND CONCLUSION: Some of NSPCs expressed FPR1 and FPR2, not only on the cell membrane, but also in the cytoplasm. The expression level of FPR1 was obviously lower than that of FPR2. The homogenate group for FPR1+ or FPR2+ NSPCs could produce more β-III tubulin-positive cells and fewer GFAP-positive astrocytes, and the effects could be blocked by FPR1 or FPR2 inhibitor Boc2 or WRW4. These experimental findings show that the spinal cord homogenate can induce FPR1 or FPR2 positive NSPCs to differentiate into neurons and inhibit their differentiation to astrocytes, and moreover, this effect is specific. 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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An in vitro study of enhancing tendon-bone healing by human amniotic mesenchymal stem cells co-modified with hypoxia-inducible factor 1 alpha and Scleraxis gene Zhu Xi-zhong, Liu Zi-ming, Liu Yi, Xiong Hua-zhang, Yang Ji-bin, Li Yu-wan, Jin Ying, Wu Shu-hong 2018, 22 (1):  113-118.  doi: 10.3969/j.issn.2095-4344.0420 Abstract ( 286 )   PDF (6945KB) ( 139 )   Save BACKGROUND: Tendon-to-bone healing is a complex and slow process, which often hinders the therapeutic outcomes. To enhance the tendon-to-bone healing, increasing cell bioactivity on the contact surface is a new strategy. Hypoxia-inducible factor 1α (HIF-1α) can induce the formation of blood vessel and bone tissue via many ways. However, it is unclear whether HIF-1α can strengthen differentiation of human amniotic mesenchymal stem cells (hAMSCs) induced by Scleraxis, a specific marker of tendon, and can be used in tendon and bone repair. OBJECTIVE: To investigate the ability of HIF-1α in enhancing Scleraxis to modify hAMSCs aiming to promote tendon-to-bone healing and its molecular mechanism. METHODS: Passage 3 hAMSCs were infected with AdHIF-1α, AdScx, AdGFP and AdHIF-1α+AdScx. The expressions of related genes of tendon, cartilage and bone tissue were detected at 3 and 7 days after infection. RESULTS AND CONCLUSION: Under the inverted phase contrast microscopy, the passage 3 hAMSCs were in spindle shape and presented with vortex-like adherent growth. Under the transmission electron microscopy, hAMSCs were in oval shape and had clear structure, with abundant endoplasmic reticulum and mitochondria. Fluorescence photographs were taken at 24 hours after adenovirus infection, showing about 50% red fluorescence expression in the AdHIF-1α group, while about 70% green fluorescence expression in the AdScx and AdGFP groups. Real time-PCR results showed that at 3 and 7 days after infection, the mRNA expressions of collagen type I, Fibronectin, RUNX2, VEGF and ALP in the AdHIF-1α+AdScx group, AdHIF-1α group and AdScx group were higher than those in the AdGFP group (P < 0.05); the mRNA expressions of collagen type I, Fibronectin, RUNX2, VEGF and ALP in the AdHIF-1α+AdScx group were significantly higher than those in the AdScx group (P < 0.05). Fluorescence immunohistochemistry results showed that the expression of collagen type I in the AdHIF-1α+AdScx group at 7 days after infection was higher than that at 3 days after infection. To conclude, HIF-1α can enhance the ability of Scleraxis to modify hAMSCs to promote tendon-to-bone healing by upregulating the expressions of molecular markers of tenocytes, chondrocytes and osteocytes. 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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The safety and efficacy of bone marrow stem cell transplantation for ischemic heart failure: a Meta-analysis Wu Ni-na, He Jian-yun, Zhu Lei, Li Xiao-mei 2018, 22 (1):  119-125.  doi: 10.3969/j.issn.2095-4344.0421 Abstract ( 277 )   PDF (2749KB) ( 148 )   Save BACKGROUND: The bone marrow stem cells (BMSCs) transplantation has been used for the treatment of ischemic heart failure in clinic. But the efficacy and safety of BMSCs transplantation remains controversial. OBJECTIVE: To systematically assess the efficacy and safety of BMSCs transplantation on ischemic heart failure through a Meta-analysis. METHODS: PubMed, Cochrane Library (Issue 10, 2016), Embase, CNKI, CBM, VIP, WanFang were search for relevant randomized controlled trials (RCTs). After data extracting and quality assessing, Meta-analysis was performed using RevMan5.3 software.   RESULTS AND CONCLUSION: A total of 8 RCTs involving 350 patients, 191 in the BMSCs group and 159 in the conventional therapy group, were included. Meta-analysis results showed that: compared with the conventional therapy, BMSCs transplantation could increase the left ventricular ejection fraction [MD=4.68, 95% CI (1.79, 7.56), P < 0.01]. But there was no significant difference in decreasing left ventricular end-diastolic volume [MD=-3.86, 95% CI (-9.90, 2.17), P=0.21] and left ventricular end-systolic volume [MD=-3.20, 95% CI (-9.21, 2.80), P=0.30]. And the incidence of adverse events was not significantly different [RR=0.85, 95% CI (0.25, 2.89), P=0.79] in the course of the treatment. Overall findings indicate that BMSCs transplantation for ischemic heart failure is safe and able to significantly increase patient’s left ventricular ejection fraction. However, BMSCs transplantation by intracoronary injection may have no effect on the left ventricular remodeling in ischemic heart failure patients. Due to the limitations of current studies, high-quality RCTs are needed to further verify our findings. 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 cells: current progress and future perspectives regarding the myogenic differentiation and use in the repair of skeletal muscle defects Chen You-bai, Zhang Wei, Li Li, Zhang Qi-xu, Han Yan 2018, 22 (1):  126-132.  doi: 10.3969/j.issn.2095-4344.0422 Abstract ( 391 )   PDF (1183KB) ( 202 )   Save BACKGROUND: Skeletal muscle defect is a major concern of plastic and orthopedic surgeons due to poor regenerative capability of skeletal myocytes and limited clinical treatment. Recently, cell therapy and skeletal muscle engineering based on adipose-derived stem cells (ADSCs) open a new era for skeletal muscle injury repair, which attributes to merits of ADSCs including sufficiency, easy harvest, high yield, strong proliferation and paracrine capability, as well as differentiation potential towards skeletal myoblasts under specific induction. OBJECTIVE: To summarize the process of ADSCs’ differentiation towards skeletal myoblasts, to analyze factors that may affect myogenic differentiation of ADSCs and their underlying mechanism, and to discuss the oncological safety of ADSC therapy and limits for clinical application. METHODS: Search in PubMed using the following formula ((myogenic[Title]) OR myogenesis[Title]) AND adipose stem cell[MeSH Terms]) and in SinoMed using (((“adipose tissue”[Title]) AND “Stem cell”[Title]) AND “myo-”[Title]) was done on June 10th, 2017. References related to ADSCs’ myogenic differentiation or skeletal muscle repair were included, whereas repeated references were excluded. RESULTS AND CONCLUSION: Forty-seven references in PubMed were selected. Within them, 26 were published in recent 5 years. Forty-seven references in SinoMed met the criteria; however 34 of them were about ADSCs’ differentiation towards myocardial cells and 6 were about ADSCs’ differentiation towards smooth muscle cells. Eventually, 50 references were included. ADSCs’ differentiation towards skeletal myoblasts under specific induction is a complicated process involving the interactions of varieties of genes, proteins and signal pathways. Besides the traditional in vitro chemical induction, conditioned medium or co-culture with myocytes can also facilitate ADSCs’ differentiation towards skeletal myoblasts. Chemicals, biomechanics, myogenic regulatory factors, cytokines, growth factors, microRNAs and lncRNA have effects on ADSCs myogenic differentiation. ADSCs can promote the repair of morphology and function of skeletal muscle through direct differentiation or indirect paracrine of cytokines, regulating inflammatory response, suppressing apoptosis, accelerating angiogenesis, and recruiting endogenous stem cells. The future study concerning skeletal muscle repair is expected to address the construction of tissue-engineered muscle by combining various cytokines and growth factors with three-dimensional scaffolds to promote ADSCs’ proliferation and differentiation.  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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Research progress of mesenchymal stem cells derived exosomes in damaged tissue repair and regeneration Li Chao-ran, Huang Gui-lin, Wang Shuai 2018, 22 (1):  133-139.  doi: 10.3969/j.issn.2095-4344.0423 Abstract ( 1051 )   PDF (1340KB) ( 368 )   Save BACKGROUND: In the past few years, many studies have shown that mesenchymal stem cells play roles in tissue repair and regeneration, which is to a large extent by their paracrine effect. As one of the important paracrine factors, exosomes have become an issue of concern for researchers. OBJECTIVE: To explain the components, sources and biological characteristics of exosomes, to summarize the latest research advances of mesenchymal stem cells derived exosomes in tissue repair and regeneration, and to make prospects of its application in the field of oral medicine. METHODS: A computer-based search of the relevant literature in CNKI and PubMed full-text databases of journals from 1983 to 2017 was performed. The keywords were “exosome, MSC-exosomes, tissue repair and regeneration, oral diseases” in Chinese and English, respectively. Totally 61 eligible articles were included in the result analysis. RESULTS AND CONCLUSION: Exosome is a vesicle secreted by cells and contains different proteins and RNAs. It plays an important role in the intercellular communication, and has the functions of inhibiting apoptosis, stimulating proliferation and regulating immunity. Mesenchymal stem cells derived exosomes play an important role in repairing bone injury, skin injury, nerve injury and liver injury, but its mechanism is yet unclear. The application of exosomes in the field of oral medicine is rarely reported, which is certainly worthy of further research and exploration. 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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Exosomes: a new strategy for mesenchymal stem cell transplantation in the treatment of osteoarthritis Luo Xin, Yu Li-mei 2018, 22 (1):  140-145.  doi: 10.3969/j.issn.2095-4344.0424 Abstract ( 352 )   PDF (1164KB) ( 201 )   Save BACKGROUND: Although mesenchymal stem cells (MSCs) and MSCs-released exosomes are expected to become a new means for osteoarthritis, the concrete molecular mechanisms remain unclear yet. OBJECTIVE: To understand the effect and mechanism of exosomes in the MSC treatment of osteoarthritis based on the main pathogenesis of osteoarthritis and characteristics of MSCs. METHODS: Domestic and foreign articles concerning MSCs and MSCs-released exosomes for the osteoarthritis treatment published from 2006 to 2016 were retrieved and analyzed. The keywords used were “exosomes, mesenchymal stem cells, osteoarthritis” in Chinese and English, respectively. RESULTS AND CONCLUSION: Osteoarthritis is a refractory disease associated with age and strain, and MSCs therapy has been obtained a good effect. Cartilage differentiation, microenvironment improvement, paracrine and exosomes mechanism of MSCs have also been reported. Exosomes play an important role in mediating intercellular signal transduction and biological responses by transferring a variety of biologically active proteins, lipids, nucleic acids and other molecules. The changes are not only related to the osteoarthritis pathogenesis, but also involved in MSCs induced regeneration and repair of bone and joint tissues. Exosomes secreted by MSCs can improve bone and joint tissue regeneration through membrane exchange and transport of active molecules. This will provide a new insight into the osteoarthritis 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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Mesenchymal stem cells for diabetic foot: existing problems and better application Xiang Jie, Zhang Jie 2018, 22 (1):  146-151.  doi: 10.3969/j.issn.2095-4344.0425 Abstract ( 573 )   PDF (959KB) ( 188 )   Save BACKGROUND: Diabetic foot is a common chronic complication of diabetes, and an increasing risk of amputation is found in such patients. The current common treatments include control of blood glucose, debridement of local tissues, anti-infection and revascularization, but none of them has achieved ideal curative effects. Further investigation on more effective treatment is needed. Recent studies have shown that mesenchymal stem cells can promote the healing of diabetic foot and improve the clinical symptoms. OBJECTIVE: To review the mechanism and clinical application of mesenchymal stem cells in the treatment of diabetic foot. METHODS: The first author searched the relevant literature (original articles and reviews) published in the PubMed and CNKI databases from 2012 to 2017, using the keywords of “mesenchymal stem cell, diabetic foot” in English and Chinese, respectively. After excluding irrelevant articles or those out of date, 44 articles fulfilling the inclusive criteria were reviewed. RESULTS AND CONCLUSION: Mesenchymal stem cells regardless of source are a promising and effect therapy for diabetic foot. Bone marrow mesenchymal stem cells have no immune limitation and are the most effective via intramuscular injection. Umbilical cord blood derived mesenchymal stem cells have some advantages, such as rich sources, short doubling time, long survival time. Adipose derived mesenchymal stem cells are widely distributed and can be easily isolated and extracted. Placenta derived mesenchymal stem cells have good proliferation ability, which are the most effective via intraperitoneal injection. Among them, bone marrow mesenchymal stem cells may be the best choice for diabetic foot 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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Melanoma stem cell markers and targeted therapies: awareness and pertinence Wu Xing, Yuan Ding-fen 2018, 22 (1):  152-157.  doi: 10.3969/j.issn.2095-4344.0406 Abstract ( 385 )   PDF (1007KB) ( 153 )   Save BACKGROUND: Melanomas, a highly malignant tumor of the skin, have no effective therapy to date. OBJECTIVE: To review the melanoma stem cell markers identified and existing therapies. METHODS: We retrieved database of CNKI and PubMed for articles addressing melanoma stem cell markers and targeted therapies, which were published from January 2010 to December 2016. The key words were “melanoma, cancer stem cell, marker, therapy” in Chinese and English, respectively. RESULTS AND CONCLUSION: Forty articles were included in the final review. It is important to separate cancer stem cells from tumor cells by tumor stem cell markers for the study of tumor growth, recurrence, metastasis and drug resistance. There are still no generally recognized markers of melanoma stem cells, but the generally studied markers are CD20, CD133, CD271, ABCB5 and SOX10. To date, we have a poor understanding of melanoma stem cell markers, and further investigations on the markers and targeted therapies are 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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Instructions for Authors (2018)-Chinese Journal of Tissue Engineering Research (CJTER) 2018, 22 (1):  158-164.  doi: 10.3969/j.issn.2095-4344.0426 Abstract ( 339 )   PDF (789KB) ( 178 )   Save Related Articles | Metrics