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08 September 2021, Volume 25 Issue 25 Previous Issue    Next Issue

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Platelet-derived growth factor BB induces bone marrow mesenchymal stem cells to differentiate into vascular endothelial cells Jiang Tao, Ma Lei, Li Zhiqiang, Shou Xi, Duan Mingjun, Wu Shuo, Ma Chuang, Wei Qin 2021, 25 (25):  3937-3942.  doi: 10.12307/2021.001 Abstract ( 495 )   PDF (1912KB) ( 92 )   Save BACKGROUND: There are few reports about platelet-derived growth factor BB promoting angiogenesis of bone marrow mesenchymal stem cells. However, the nutrition, growth factors and cytokines provided by neovascular network play an important role in bone tissue formation. OBJECTIVE: To investigate the effects of platelet-derived growth factor-BB on the differentiation of bone marrow mesenchymal stem cells of Sprague-Dawley rats into vascular endothelial cells.  METHODS:  (1) Bone marrow mesenchymal stem cells of Sprague-Dawley rats were isolated and cultured in vitro. The surface markers CD45, CD29 and CD34 of the third generation were identified by flow cytometry. Bone marrow mesenchymal stem cells with high purity were selected for platelet-derived growth factor BB intervention experiments. (2) Passage 3 bone marrow mesenchymal stem cells were induced by 25 μg/L platelet-derived growth factor BB for 3 days. Matrigel was selected for cell lumen formation experiments. The immunofluorescence method was used to detect the expression of FITC-UEA-1 and DIL-ac-LDL in cells to verify the fluorescence expression of CD31 in cells. Flow cytometry was used to detect the expression of CD31 in cells after induction. Finally, the mRNA level of vascular endothelial growth factor gene was detected by RT-PCR.    RESULTS AND CONCLUSION: The cells were mixed with Matrigel and inoculated after platelet-derived growth factor BB induction. A clear tubular structure was formed; the expressions of FITC-UEA-1 and DIL-ac-LDL and CD31 expression were positive in bone marrow mesenchymal stem cells after induction. The expression of VEGF mRNA in platelet-derived growth factor BB-induced cells was higher than that in bone marrow mesenchymal stem cells without platelet-derived growth factor BB (P < 0.05). It is concluded that rat bone marrow mesenchymal stem cells can differentiate into functional vascular endothelial cells after being induced by platelet-derived growth factor BB. Figures and Tables | References | Related Articles | Metrics

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C-jun, Cytc and Caspase-9 in the apoptosis of cerebellar granule neurons induced by diacetylmorphine in rats Su Liping, Lu Ziyang, Liu Li, Zhang Wei, Su Tianyuan, Hu Xiayun, Pu Hongwei, Han Dengfeng 2021, 25 (25):  3943-3948.  doi: 10.12307/2021.002 Abstract ( 511 )   PDF (3106KB) ( 49 )   Save BACKGROUND: Diacetylmorphine drugs can cause neuronal injury, but whether diacetylmorphine induces neuronal apoptosis or whether c-Jun, cytc and caspase-9 factors are involved in this process have not been reported.  OBJECTIVE: To investigate whether C-jun, Cytc, and Caspase-9 are involved in apoptosis induced by diacetylmorphine. METHODS:  The cerebellar granule neurons of SD suckling mice were cultured in vitro for 7 days. Different concentrations of diacetylmorphine (0, 10, 40, 80, 100, 120 mg/L) were used to intervene neurons for 24 hours. The morphological changes of neurons were observed by inverted fluorescence microscope, and the apoptosis rate was detected by flow cytometry. The cells were treated with 100 mg/L diacetylmorphine and 20 μmol/L JNK inhibitor SP600125 for 24 hours. The expressions of c-jun, cytc and caspase-9 protein were detected by immunofluorescence and western blot assay. RESULTS AND CONCLUSION: (1) With the increase dosages of diacetylmorphine, the neuronal cell body of neurons shrank, the brightness decreased, some of them were gray black, the cells were fragmented, the neuron network structure disappeared in different degrees and the number of cell changes increased gradually. (2) With the increase of the concentration of the drug, the number of morphological changes increased obviously (P < 0.01), and the apoptosis rate also increased significantly (P < 0.01). (3) Compared with the control group, c-jun, cytc and caspase-9 proteins were highly expressed in the diacetylmorphine group when treated with 100 mg/L diacetylmorphine and the difference was statistically significant (P < 0.05). Compared with the diacetylmorphine group, c-jun, cytc, and caspase-9 protein expression was significantly down-regulated in the diacetylmorphine+SP600125 group (P < 0.05). (4) The results indicate that diacetylmorphine can induce apoptosis of cerebellar granule neurons. The c-jun, cytc, and caspase-9 are involved in neuronal apoptosis induced by diacetylmorphine. Figures and Tables | References | Related Articles | Metrics

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Low-intensity pulsed ultrasound promotes the proliferation and adhesion of human adipose-derived mesenchymal stem cells Chen Yang, Huang Denggao, Gao Yuanhui, Wang Shunlan, Cao Hui, Zheng Linlin, He Haowei, Luo Siqin, Xiao Jingchuan, Zhang Yingai, Zhang Shufang 2021, 25 (25):  3949-3955.  doi: 10.12307/2021.003 Abstract ( 456 )   PDF (2244KB) ( 82 )   Save BACKGROUND: Mesenchymal stem cells are one of the hot topics in tissue engineering and regenerative medicine. However, how to effectively expand the stem cells in vitro to meet the clinical needs is still a challenge for researchers. OBJECTIVE: To investigate the effect of low-intensity pulsed ultrasound on the proliferation and adhesion of human adipose-derived mesenchymal stromal cells. METHODS:  The human adipose-derived mesenchymal stromal cells of the passage 3 were cultured for 24, 48 and 72 hours. The first, second and third times of stimulation were performed with 0, 10, 30, and 50 mW/cm2 low-intensity pulsed ultrasound intensity, and each stimulation time was 5 minutes. After the stimulation, the cells were placed in the incubator for 24 hours. CCK-8 test was used to screen the best stimulation conditions. The cells stimulated twice with 30 mW/cm2 were selected as the experimental group for follow-up experiments, and 0 mW/cm2 for the control group. Flow cytometry was used to detect cell surface markers. Immunohistochemistry was used to observe the expression of proliferation related antigen Ki-67 and focal adhesion kinase FAK. RT-PCR was used to detect the expression of Cyclin D1 and c-myc. Transcriptome sequencing was used to detect the changes of transcription genes.  RESULTS AND CONCLUSION: (1) 30 mW/cm2 continuous stimulation twice was the best condition to promote the proliferation of human adipose-derived mesenchymal stem cells. (2) Compared with the control group, cell surface markers remained unchanged after 30 mW/cm2 low-intensity pulsed ultrasound stimulation, and the expression of proliferation-related genes CyclinD1, c-myc and focal adhesion kinase FAK were up-regulated. (3) Transcriptome sequencing results showed that there were significant differences in 27 genes, among which 15 genes were up-regulated and 12 genes were down-regulated. (4) It is concluded that low-intensity pulsed ultrasound promotes human adipose-derived mesenchymal stromal cells proliferation in undifferentiated cells by upregulating the expression of CyclinD1, c-myc and FAK, accompanied by regulation of multiple transcriptome genes.  Figures and Tables | References | Related Articles | Metrics

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Effects of human growth hormone on proliferation and osteogenic differentiation of human periodontal ligament stem cells Yang Junhui, Luo Jinli, Yuan Xiaoping 2021, 25 (25):  3956-3961.  doi: 10.12307/2021.004 Abstract ( 416 )   PDF (2630KB) ( 70 )   Save BACKGROUND: Growth hormone has been proven to promote the proliferation and bone differentiation of non-dental mesenchymal stem cells, but the biological effect on human periodontal ligament stem cells is still unclear. OBJECTIVE: To explore the effect of human growth hormone on the proliferation and osteogenic differentiation of human periodontal ligament stem cells.  METHODS: The α-MEM complete medium containing 0 (control group), 10, 100, 200 μg/L human growth hormone was added to the third generation of human periodontal ligament stem cells. CCK-8 assay was used to detect cell proliferation at 1, 3, 5, and 7 days. The osteoinductive fluids containing 0 (control group), 10, 100, 200 μg/L human growth hormone was added to the third generation of human periodontal ligament stem cells. At 7 days, real-time PCR and western blot assay were used to detect the gene and protein expression of the bone differentiation-related factors opn and runx2. At 14 days, Alizarin Red staining and Alizarin Red semi-quantitative detection were used to analyze the mineralization of human periodontal ligament stem cells in the late stage of osteogenic formation.     RESULTS AND CONCLUSION: The cell proliferation of 100 and 200 μg/L groups was significantly better than that of the control group (P < 0.05). The gene and protein expression of opn and runx2 was higher in the 100 and 200 μg/L groups than that in the control group (P < 0.05). The mineralization of human periodontal ligament stem cells in the 100 and 200 μg/L groups was better than that of the control group (P < 0.05). Results confirm that in vitro experiments, human growth hormone at concentrations of 100 and 200 μg/L can promote the proliferation and osteogenic differentiation of human periodontal ligament stem cells.  Figures and Tables | References | Related Articles | Metrics

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Effect of montelukast combined with bone marrow mesenchymal stem cell transplantation on spinal cord injury in rat models Sun Jianwei, Yang Xinming, Zhang Ying 2021, 25 (25):  3962-3969.  doi: 10.12307/2021.005 Abstract ( 484 )   PDF (2578KB) ( 62 )   Save BACKGROUND: Combination with a variety of treatment methods can effectively intervene for different targets, play a synergistic or superimposed effect, and has become a new concept of clinical treatment of spinal cord injury.  OBJECTIVE: To investigate the effect of montelukast combined with bone marrow mesenchymal stem cell transplantation on the recovery of neurological function in rats with spinal cord injury. METHODS:  Sixty 8-week-old healthy male Sprague-Dawley rats were randomly divided into four groups, each with 15 rats, namely model group, montelukast group, bone marrow mesenchymal stem cell group, and combination group. The spinal cord injury model was performed in each group according to the Allen method, and montelukast 5 mg/kg or the equivalent amount of normal saline was administered by gavage at 1 and 6 hours after the model was successfully established, and then once a day for 30 days. At 2 hours after modeling, 1 μL of BrdU-labeled bone marrow mesenchymal stem cell suspension or an equivalent amount of PBS was injected into the spinal cord injury area at a time. At 1, 3, 7, 14, 21, and 30 days after modeling, the BBB score and Rivlin inclined plate test were used to evaluate the motor function of the rat’s hind limbs. At 7 days after modeling, the histopathological changes of spinal cord were observed by hematoxylin-eosin staining and Nissl staining. Immunohistochemical method was applied to detect the expression of glial fibrillary acidic protein, interleukin-1β and BrdU positive labeling rate in rat spinal cord tissue. Western blot assay was used to detect the expression of apoptosis-related proteins Bcl-2, Bax and Caspase-3 in rat spinal cord tissue.  RESULTS AND CONCLUSION: (1) At 7, 14, 21, and 30 days after modeling, the BBB score and Rivlin inclined plate test results of the combination group, montelukast group and bone marrow mesenchymal stem cell group were significantly higher than those of the model group (P < 0.05). (2) At 7 days, , the inflammatory reaction and edema were reduced; the area of injury cavity and glial scar was reduced; and the structure of damaged segment was improved in combination group, montelukast group and bone marrow mesenchymal stem cell group. (3) At 7 days, the expressions of glial fibrillary acidic protein and interleukin-1β in combination group, montelukast group and bone marrow mesenchymal stem cell group were significantly lower than those in the model group (P < 0.05). The positive rate of BrdU in combination group was higher than that in bone marrow mesenchymal stem cell group (P=0.000). (4) At 7 days, the expression levels of Bax and Caspase-3 in combination group, montelukast group and bone marrow mesenchymal stem cell group were significantly lower than those in the model group (P < 0.05); the expression of Bcl-2 was significantly higher than that in the model group (P < 0.05). (5) All the above indexes in combination group were better than those in montelukast group and bone marrow mesenchymal stem cell group. (6) The results show that montelukast combined with bone marrow mesenchymal stem cells transplantation can significantly improve the neuromotor function of rats after spinal cord injury. The mechanism may be related to inhibiting local inflammatory response and glial cell proliferation, reducing the expression of apoptosis-related proteins, and increasing the survival rate of bone marrow mesenchymal stem cell transplantation. Figures and Tables | References | Related Articles | Metrics

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Alpl gene affects the therapeutic effect of bone marrow mesenchymal stem cells on ulcerative colitis Zhang Lishu, Liu Anqi, He Xiaoning, Jin Yan, Li Bei, Jin Fang 2021, 25 (25):  3970-3975.  doi: 10.12307/2021.006 Abstract ( 381 )   PDF (2719KB) ( 66 )   Save BACKGROUND: Transplantation of bone marrow mesenchymal stem cells in the treatment of ulcerative colitis has achieved remarkable results, but the specific mechanism remains elusive. OBJECTIVE: To observe and explore the role of Alpl gene in bone marrow mesenchymal stem cells on the treatment of ulcerative colitis. METHODS:  (1) Alpl+/- mice and wild-type mice were raised and bred for genotyping. (2) Bone marrow mesenchymal stem cells Alpl+/- mice and wild-type mice were cultured in vitro, and cell growth was observed. Osteoblasts induction and flow cytometry assay were performed for stem cell characterization by detecting cell surface markers. (3) Twenty-four C57BL/6 mice were randomly divided into normal group, model control group, wild-type mouse bone marrow mesenchymal stem cell treatment group, and Alpl+/- mouse bone marrow mesenchymal stem cell treatment group. The latter three groups were fed with 3% dextran sulfate sodium solution for 7 days to induce ulcerative colitis in mice. Bone marrow mesenchymal stem cells from wild-type mice and Alpl+/- mice were injected via tail vein on day 3 and day 5 after administration of dextran sulfate sodium solution. On day 10, the colon tissue was collected. (4) Daily body weight changes were recorded and disease activity index was calculated. Colon length was compared. Hematoxylin-eosin staining was used to observe and compare the histological changes of colonic mucosa.   RESULTS AND CONCLUSION: (1) The genotype identification showed that the heterozygotes were double bands, which was consistent with the prediction results provided by The Jackson Laboratory, indicating the Alpl+/- mice were successfully obtained. (2) Both groups of cells could form reddish brown osteogenic nodules, and both expressed classical mesenchymal stem cells markers CD146 and CD73. However, compared with wild-type bone marrow mesenchymal stem cells, Alpl+/- mouse bone marrow mesenchymal stem cells had various morphology and lack of long spindle cells with clear boundary. (3) Compared with the model control group, the enteritis symptoms and pathological changes of the two treatment groups were reduced, but the treatment effect of wild-type mouse bone marrow mesenchymal stem cell group was significantly better than that of Alpl+/- mouse bone marrow mesenchymal stem cell group. (4) The results suggest that bone marrow mesenchymal stem cell transplantation can treat ulcerative colitis induced by dextran sulfate sodium, and Alpl gene mutation inhibits the therapeutic effect of bone marrow mesenchymal stem cells on ulcerative colitis. Figures and Tables | References | Related Articles | Metrics

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Human placenta derived mesenchymal stem cell gel promotes the healing of radiation skin damage in SD rats Xu Xiaoming, Chen Yan, Song Qian, Yuan Lu, Gu Jiaming, Zhang Lijuan, Geng Jie, Dong Jian 2021, 25 (25):  3976-3980.  doi: 10.12307/2021.007 Abstract ( 498 )   PDF (1208KB) ( 47 )   Save BACKGROUND: Radiation skin injury has always been a difficult problem in clinical radiotherapy of tumors. A large number of experimental studies have shown that human placenta derived mesenchymal stem cells have the potential for epidermal cell differentiation and can promote the healing of wounded skin. OBJECTIVE: To evaluate the effect of local application of human placenta derived mesenchymal stem cell gel on the healing of radiation skin damage in rats.  METHODS:  Twenty-three Sprague-Dawley rats were randomly divided into three groups: negative control group (n=3), blank gel group (n=10) and mesenchymal stem cell gel group (n=10). Each group received skin irradiation of buttock and back (6 meV electron wire, total dose of 50 Gy, irradiation field of 3 cm×3 cm, single dose rate of 500 cGy/min). At 23 days after irradiation, the wounds of the mesenchymal stem cell gel group were smeared with human placenta derived mesenchymal stem cell gel. The blank gel control group was smeared with blank gel evenly, once a day, for six times. The negative control group was not given any treatment. The wound healing was observed once every four days. After 28 days of treatment, the effects of human placenta derived mesenchymal stem cell gel on inflammatory cells, wound microvessel density and wound collagen fibers were observed.  RESULTS AND CONCLUSION: (1) The skin in the negative control group was swollen and ulcerated; the skin in the blank gel group was stiff and shrunken; and the wounds did not heal during the observation. The mesenchymal stem cell gel group developed new epithelial tissue in the irradiation area, and the wound healing was complete during the observation. (2) Compared with negative control and blank gel groups, at 16, 20, 24, and 28 days after treatment, the wound healing speed of the mesenchymal stem cell gel group was significantly faster (P < 0.05), and wound area was significantly reduced (P < 0.05); the count of inflammatory cells was lower (P < 0.05); count of CD31 cells in microvessel was significantly higher (P < 0.05); collagen fibers were arranged orderly. (3) The results indicate that local application of human placenta derived mesenchymal stem cell gel can promote the healing of radiation skin damage in SD rat.  Figures and Tables | References | Related Articles | Metrics

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Comparison on the curative effect of human placenta-derived mesenchymal stem cells and induced islet-like cells in gestational diabetes mellitus rats Gao Shan, Huang Dongjing, Hong Haiman, Jia Jingqiao, Meng Fei 2021, 25 (25):  3981-3987.  doi: 10.12307/2021.008 Abstract ( 378 )   PDF (2850KB) ( 122 )   Save BACKGROUND: Gestational diabetes can cause serious damage to maternal and fetal health. Exploring safe and effective methods on gestational diabetes prevention and treatment has become one of the important research directions of obstetrics and gynecology. OBJECTIVE: To compare the therapeutic effects of human placenta-derived mesenchymal stem cells and islet-like cells on gestational diabetes mellitus rats, so as to provide theoretical basis for clinical research on the treatment of gestational diabetes mellitus. METHODS:  Human placenta-derived mesenchymal stem cells were extracted from human placental tissue under aseptic conditions, then the identified stem cells were induced into islet-like cells. Flow cytometry was used to detecte the expressions of insulin and nestin protein in differentiated cells and dithizone staining was used to identify the expression of zinc ions in islet-like cell clusters. Female Sprague-Dawley rats were divided into five groups (n=10 per group): Normal pregnant rats group, gestational diabetes mellitus rats without intervention group, gestational diabetes mellitus rats saline intervention group, gestational diabetes mellitus rats human placenta-derived mesenchymal stem cells intervention group and gestational diabetes mellitus rats islet-like cells intervention group. Gestational diabetes mellitus model was established by feeding high-glucose and high-fat diet before pregnancy and intraperitoneal injection of streptozotocin after pregnancy. After successful modeling, 1 mL normal saline suspension containing 6×106 human placenta-derived mesenchymal stem cells or islet-like cells was injected via tail vein. The fasting blood glucose and body weight of rats in each group were measured at 6, 12, and 18 days of pregnancy, and the serum adiponectin level of pregnant rats was detected at 18 days of pregnancy.    RESULTS AND CONCLUSION: (1) During the differentiation of human placenta-derived mesenchymal stem cells into islet-like cells, the insulin level increased and the nestin level increased then decreased gradually. The islet-like cell clusters formed at 28 days. (2) Both human placenta-derived mesenchymal stem cells and islet-like cells treatment were effective on reducing blood glucose and promoting adiponectin levels as well as body weight. At 18 days, compared with human placenta-derived mesenchymal stem cells, islet-like cells reduced blood glucose and increased adiponectin levels and body weight more significantly. (3) The results indicate that both human placenta-derived mesenchymal stem cells and islet-like cells treatments were effective on gestational diabetes mellitus rats. Islet-like cells induced by human placenta-derived mesenchymal stem cells treatment were more effective than that of the uninduced human placenta-derived mesenchymal stem cells. Figures and Tables | References | Related Articles | Metrics

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Bone marrow mesenchymal stem cells overexpressing prolyl oligopeptidase on the repair of liver fibrosis in rat models Hao Xiaona, Zhang Yingjie, Li Yuyun, Xu Tao 2021, 25 (25):  3988-3993.  doi: 10.12307/2021.009 Abstract ( 427 )   PDF (2698KB) ( 147 )   Save BACKGROUND: How to make the transplanted mesenchymal stem cells survive and function better is one of the hot spots in the research of mesenchymal stem cells. OBJECTIVE: To investigate the repair function of bone marrow mesenchymal stem cells overexpressing prolyl oligopeptidase on liver fibrosis in rats and explore the related mechanisms. METHODS:  Five rats were randomly selected from 35 male Sprague-Dawley rats into the normal control group (n=5). The remaining 30 rats were injected subcutaneously with CCl4 peanut oil solution to prepare rat liver fibrosis models. After successful modeling, they were randomly divided into model injury group (n=10), bone marrow mesenchymal stem cells group (n=10), and prolyl oligopeptidase-overexpressed bone marrow mesenchymal stem cells group (n=10). The model injury group was given normal saline via the tail vein. Bone marrow mesenchymal stem cells group was given 1×106 bone marrow mesenchymal stem cells. The prolyl oligopeptidase overexpression bone marrow mesenchymal stem cells group was given 1×106 prolyl oligopeptidase-overexpressed bone marrow mesenchymal stem cells. Three weeks later, the rats were sacrificed. The inferior vena cava blood of each group was collected to detect liver function and liver fibrosis indicators. The liver was taken out and stained with hematoxylin-eosin to observe the pathological changes. Cell localization was observed under a fluorescence microscope. Western blot assay was conducted to detect the expression level of transforming growth factor-β protein in the liver.   RESULTS AND CONCLUSION: (1) The liver function and fibrosis indexes of rats in the bone marrow mesenchymal stem cells group and prolyl oligopeptidase-overexpressed bone marrow mesenchymal stem cells group were significantly improved compared with the model injury group, and the improvement was more obvious in the prolyl oligopeptidase-overexpressed bone marrow mesenchymal stem cells group (P < 0.05). (2) Fluorescence microscope of frozen section of rat liver tissue showed that there were green fluorescent cells in the prolyl oligopeptidase-overexpressed bone marrow mesenchymal stem cells group, indicating that bone marrow mesenchymal stem cells were successfully colonized in the rat liver. (3) Hematoxylin-eosin staining of liver tissue indicated that the degree of liver fibrosis in the bone marrow mesenchymal stem cells and prolyl oligopeptidase-overexpressed bone marrow mesenchymal stem cells groups was significantly improved, and the liver pathology of the prolyl oligopeptidase-overexpressed bone marrow mesenchymal stem cells group was closer to normal. (4) The expression level of transforming growth factor-β protein in the bone marrow mesenchymal stem cells group and prolyl oligopeptidase-overexpressed bone marrow mesenchymal stem cells group was significantly lower than that of the model injury group (P < 0.05), and the decrease in the prolyl oligopeptidase-overexpressed bone marrow mesenchymal stem cells group was more obvious (P < 0.05). (5) Results verify that overexpression of prolyl oligopeptidase can significantly improve the repair ability of bone marrow mesenchymal stem cells on liver fibrosis. Figures and Tables | References | Related Articles | Metrics

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Umbilical cord mesenchymal stem cell transplantation for traumatic systemic inflammatory response syndrome in tree shrews Ruan Guangping, Yao Xiang, Liu-Gao Miyang, Cai Xuemin, Li Zian, Pang Rongqing, Wang Jinxiang, Pan Xinghua 2021, 25 (25):  3994-4000.  doi: 10.12307/2021.010 Abstract ( 333 )   PDF (8149KB) ( 40 )   Save BACKGROUND: The research on the prevention and treatment of war trauma has always been the core content in the field of military medicine. It is of great military and scientific significance to establish repeatable animal models of war traumatic infection, systemic inflammatory response syndrome, shock, multiple organ failure and new treatment methods based on the animal model.  OBJECTIVE: To investigate the efficacy of umbilical cord mesenchymal stem cells in the treatment of traumatic systemic inflammatory response syndrome.  METHODS:  Totally 40 out of 50 tree shrews were used to establish the model of traumatic systemic inflammatory response syndrome by intravenous injection of lipopolysaccharide after unilateral femoral comminuted fracture using the impact method. The other 10 tree shrews were used as normal controls. After the model was established for 10 days, umbilical cord mesenchymal stem cells labeled with GFP were transfused through tail vein of 20 tree shrews, and 18 were not reinfused as model control group. The distribution of GFP-labeled cells in vivo was measured in each group at 2 and 10 days after GFP-labeled UCMSCs injection. At 20 days after cell transplantation, samples were taken to observe the pathological changes of each tissue, and peripheral venous blood samples were taken to examine the changes in liver function, renal function and heart function.    RESULTS AND CONCLUSION: (1) GFP-positive cell distribution was observed in all tissues at 2 and 10 days after cell transplantation. The distribution of GFP-positive cells in pancreatic tissue was more obvious at 2 days after transplantation, and more GFP-positive cells were found in liver tissue 10 days after transplantation. (2) At 20 days after transplantation, hematoxylin eosin staining results showed that cell necrosis and inflammatory cell infiltration were observed in each organ of the model control group, and the treatment group was close to the normal control group. The results of liver function, renal function and heart function in the treatment group returned to normal. (3) These results indicate that umbilical cord mesenchymal stem cells have a certain effect on the treatment of traumatic systemic inflammatory response syndrome, and this method provides a new technical solution for treatment of modern weapon trauma. Figures and Tables | References | Related Articles | Metrics

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Bibliometric and visualization analysis of breast cancer stem cell literature from 2011 to 2020 based on Web of Science database Lu Yuyun, Huang Mei, Shi Xinlei, Chen Baoyan 2021, 25 (25):  4001-4008.  doi: 10.12307/2021.011 Abstract ( 503 )   PDF (3721KB) ( 294 )   Save BACKGROUND: It has been recognized that breast cancer stem cells play an important role in the occurrence, development, metastasis, recurrence and drug resistance of breast cancer, but the action mechanism of breast cancer stem cells in it is still unclear, and the treatment of breast cancer needs further improvement. OBJECTIVE: To explore the research status and development trend in the field of breast cancer stem cells from 2011 to 2020.  METHODS:  The relevant literature data in the field of breast cancer stem cell research were obtained from the Web of Science database, and the two-dimensional bar diagram of the corresponding data was drawn by Microsoft excel 2019. The co-occurrence analysis function of VOSviewer software was used to draw the co-occurrence analysis chart of keywords and its superposition with time.     RESULTS AND CONCLUSION: (1) A total of 1 013 papers were included in this study. The number of papers, the H index, and the number of citations from the United States were the first in the world. The number of the literature on oncology is the largest. Sun Yat-Sen University is the largest producer of literature. WICHA MS is the author with the largest number of publications. National Natural Science Foundation of China supports the largest number of outputs. The largest number of publications is published in the ONCOTARGET. (2) The combination of chemotherapy and metformin and targeted antiangiogenic therapy are the key research contents in oncology. (3) In gene genetics, sox2, ezh2, and nanog are the key genes. (4) In the treatment of breast cancer stem cells, epithelial-mesenchymal transition is the main research content. (5) In molecular biology, cd24 and cd44 are the key biomarkers. (6) “Nuclear factor-κB” and “stemness” are the closest keywords to the present time. (7) Recombinant human receptor tyrosine kinase HRG/ErbB3 signals related to the nuclear factor-κB pathway, Pterostilbene and disulfiram are the research focus, and the epithelial/mesenchymal heterogeneity, miR34a-NOTCH1 axis and LINC00511/miR-185-3p/E2F1/Nanog axis related to the stemness of breast cancer stem cells are the key research contents. (8) The United States has the highest link intensity with other countries in co-country analysis. (9) It is concluded that in the field of breast cancer stem cells, the United States is the most powerful country. The research direction in this field is gradually tending to the application of breast cancer stem cells to the treatment of breast cancer. The research of nuclear factor-κB and stemness may be the current research hotspots in this field. Figures and Tables | References | Related Articles | Metrics

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Next-generation sequencing of identifying the human leukocyte antigen-A*24:353 and its gene frequency analysis He Liumei, Chen Hao, Zhong Yanping, Quan Zhanrou, Zou Hongyan 2021, 25 (25):  4009-4012.  doi: 10.12307/2021.012 Abstract ( 429 )   PDF (1089KB) ( 37 )   Save BACKGROUND: High resolution validation of human leukocyte antigen (HLA) is one of the essential step before hematopoietic stem cell transplantation. With the continuous development of the work and the number of people tested continues to increase, human leukocyte antigen new alleles are constantly emerging. Due to the late discovery of some new genes and the lack of relevant reports, the gene frequency cannot be accurately calculated. In the absence of relevant data, it is easy to misjudge the typing results. The result of mismatch affects the success rate of transplantation.  OBJECTIVE: An allele of HLA-A*24:353 was detected and confirmed in HLA, and its occurrence frequency was analyzed. METHODS:  Polymerase chain reaction-sequencing-based typing method was used to detect five loci of HLA- A, B, C, DRB1, and DQB1 in 543 clinical transplantation matching recipients from September 2019 to May 2020. Next-generation sequencing was used to determine the full-length sequence of HLA-A*24:02/24:353 ambiguous results to obtain high resolution typing results of HLA and calculate the occurrence frequency of HLA-a *24:353 gene. RESULTS AND CONCLUSION: The ambiguous results of HLA-A*24:02/24:353 were detected in 146 cases. After further confirmatory tests using next-generation sequencing, the results of HLA-A*24:353 gene were detected in 5 cases (3.42%) in A*24 group and 0.92% in 543 cases. The results suggest that HLA-A*24:353 may not be rare allele in China. When HLA-A*24:02/24:353 ambiguous results appear in clinical transplantation matching recipients for high resolution typing, further confirmation is needed to increase the accuracy of typing results and improve the success rate of transplantation matching. Figures and Tables | References | Related Articles | Metrics

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Macrophage migration inhibition factor promotes bone marrow mesenchymal stem cells homing to repair acute knee cartilage injury Lu Dinggui, Yao Shunhan, Tang Qianli, Tang Yujin 2021, 25 (25):  4013-4018.  doi: 10.12307/2021.013 Abstract ( 349 )   PDF (1877KB) ( 55 )   Save BACKGROUND: Cartilage lacks blood vessels and nerves, so its ability to repair itself is limited. The main method of young people’s cartilage repair is subchondral bone drilling and microfracture surgery. The purpose is to open up the subchondral bone plate and make bone marrow mesenchymal stem cells home to the injured area. Bone marrow mesenchymal stem cells differentiate into chondrocytes and fibroblasts to play a repair role. The growth rate of cartilage after microfracture surgery depends on the number of stem cells in the injured area. Therefore, increasing the number of stem cells homing can increase the chance of successful surgery.  OBJECTIVE: To explore the effect of macrophage migration inhibition factor on bone marrow mesenchymal stem cells homing treatment of acute cartilage injury.  METHODS:  Bone marrow mesenchymal stem cells were obtained from the bone marrow of the human femur, and then cultured. The ability of bone marrow mesenchymal stem cells to differentiate into chondrocytes was tested. The CXCR2 receptor expression of bone marrow mesenchymal stem cells and chondrocytes was measured by immunohistochemical method. The effect of macrophage migration inhibition factor on the migration kinetics of bone marrow mesenchymal stem cells was investigated by cell scratch test. A rat model of acute knee articular cartilage injury was made, and macrophage migration inhibition factor was injected intra-articularly at 1, 2, and 3 days after model establishment. Immunofluorescence staining and flow cytometry were used to detect the number of PECAM-1 positive cells (vascular endothelial cells) in the injured area, and DAPI staining was used to detect the number of monocytes in the damaged area.    RESULTS AND CONCLUSION: (1) The surface markers of bone marrow mesenchymal stem cells were positive for CD166, CD29, and negative for CD34. (2) The CXCR2 antibody phenotype degenerated and disappeared after bone marrow mesenchymal stem cells differentiated into chondrocytes, while the phenotype expression of type 2 collagen antibody was positive. (3) Macrophage migration inhibition factor could promote the migration of bone marrow mesenchymal stem cells. After blocking the CXCR2 receptor of bone marrow mesenchymal stem cells, the effect of macrophage migration inhibition factor on promoting the migration of bone marrow mesenchymal stem cells was inhibited. (4) In animal models, the results of DAPI staining indicated that the number of nucleated cells in the injured area of the macrophage migration inhibition factor group was higher than that of the control group. Immunofluorescence staining and flow cytometry showed that the number of PECAM-1 positive cells in the repaired area of the macrophage migration inhibition factor group was higher than that of the control group. (5) The above results show that overexpression of macrophage migration inhibition factor promotes bone marrow mesenchymal stem cells to homing and repair acute cartilage damage.  Figures and Tables | References | Related Articles | Metrics

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Comparison of different human cell derived induced pluripotent stem cells and embryonic stem cells in tuning embryoid body differentiation Wei Yunjian, Zhang Fengbo, Long Ping, Jiang Xinxing, Ma Yanlin, Sun Fei, Li Qi 2021, 25 (25):  4019-4024.  doi: 10.12307/2021.014 Abstract ( 467 )   PDF (2180KB) ( 99 )   Save BACKGROUND: Induced pluripotent stem cells (iPSCs) without virus vector integration can be successfully induced by small molecule compounds and plasmid transfection. Similar to embryonic stem cells, iPSCs can differentiate freely into hematopoietic progenitor cells. However, it is not clear whether exogenous factors and human cells from different sources affect the differentiation of iPSCs and hematopoietic progenitor cells. OBJECTIVE: To compare the gene expression differences between iPSCs of different cell sources and embryoid bodies of embryonic stem cells, so as to explore the clinical transformation of iPSCs.   METHODS:  The iPSCs and human embryonic stem cells were constructed from amniotic cells-derived cells and urine cells-derived cells. The different days of embryoid bodies were collected to test the expression of pluripotent genes Oct4, Sox2 and Nanog, endoderm marker gene GATA4, mesoderm marker gene MSX1, ectoderm marker gene PAX6, hematopoietic stem cell marker genes CD34/CD43.   RESULTS AND CONCLUSION: (1) The expression of Oct4/Sox2/Nanog in embryoid bodies from amniotic fluid cells derived iPSCs was almost undetectable at 8 days, which was different from urine cells derived iPSCs and embryoid bodies embryonic stem cells. They could sustain expression until 16 days. (2) The expression peak of GATA4/MSX1/PAX6 in embryoid bodies from amniotic fluid cells derived iPSCs was at 4 days, and sustained expression at 8-12 days. The expression peak of GATA4/MSX1/PAX6 in embryoid bodies from urine cells derived iPSCs and embryonic stem cells was at 4-8 days, and sustained expression at 12-16 days. The expression level of three layer-differentiation markers for embryoid bodies from urine cells derived iPSCs were significantly higher than iPSCs from amniotic fluid cells and embryonic stem cells. (3) At 12 days, the ratio of hematopoietic stem cell was the most in embryoid bodies from amniotic fluid cells and urine cells derived iPSCs. However, the ratio in the embryoid bodies from embryonic stem cells was at 4 days. The hematopoietic stem cell ratio was higher in embryoid bodies from urine cells derived iPSCs than that in amniotic fluid cells and embryonic stem cells. (4) Embryoid bodies from different cells derived iPSCs and embryonic stem cells all had pluripotency and the ability of three layer-differentiation, but they were distinctive. Urine cells derived iPSCs may replace embryonic stem cells as hematopoietic cell differentiation model in vitro. Figures and Tables | References | Related Articles | Metrics

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Regulation of S100A4 gene silencing by ultrasound microbubbles on the stemness and epithelial-mesenchymal transformation of gastric cancer stem cells#br# Xu Guilan, Song Jiansheng, Yang Shijiang 2021, 25 (25):  4025-4031.  doi: 10.12307/2021.015 Abstract ( 243 )   PDF (1706KB) ( 197 )   Save BACKGROUND: S100A4 is a member of S100 family of calcium binding proteins, which can bind to the corresponding target proteins, and then have an important impact on the proliferation and metastasis of tumor cells and pluripotent stem cells. Recent studies have shown that ultrasound targeted destruction of microbubbles can enhance gene transfection efficiency. OBJECTIVE: To study the effect of S100A4 gene silencing by ultrasound targeted microbubble destruction on the stemness and epithelial-mesenchymal transformation of gastric cancer stem cells. METHODS:  SGC-7901 human gastric cancer stem cells in logarithmic growth phase were harvested to isolate tumor stem cell spheres by serum-free suspension culture. The expression of EpCAM+CD44+ on the surface of tumor stem cells was detected by flow cytometry. The expression plasmid targeting S100A4 gene was constructed and transfected into EpCAM+CD44+ gastric cancer stem cells by ultrasound microbubble. At 48 hours after transfection, S100A4 expression was detected by western blot assay. The proliferation, clone formation, migration and invasion of gastric cancer stem cells were detected by CCK-8, clone formation test and Transwell cell. The expression of markers related to epithelial mesenchymal transformation was detected by western blot assay and qRT-PCR. RESULTS AND CONCLUSION: Flow cytometry results showed that the proportion of EpCAM+CD44+ cells after enrichment of gastric cancer stem cells was significantly higher than that before enrichment (P < 0.05). The expression of S100A4 protein in the transfected group was significantly lower than that in the untransfected group (P < 0.01). At 48 hours after transfection, the proliferation rate, clone-forming ability, migration and invasion ability of gastric cancer stem cells significantly decreased, the expression of E-cadherin increased, and the expression of N-cadherin and Vimentin decreased. These findings indicate that RNA interference with S100A4 gene can inhibit the proliferation, clone-forming ability, migration and invasion of gastric cancer stem cells by regulating the expression of E-cadherin, N-cadherin and Vimentin. Related Articles | Metrics

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Effects of different induced polarization methods on the proliferation, apoptosis and phagocytosis of rat bone marrow-derived macrophages Li Li, Zhuo Jin, Zheng Ling, Zhou Ling, Wang Qisong, Luo Lan, Luo Kai 2021, 25 (25):  4032-4037.  doi: 10.12307/2021.016 Abstract ( 474 )   PDF (1724KB) ( 53 )   Save BACKGROUND: Classically activated and alternative activated macrophages have different phenotypes and functions, and there are few studies to explore the effect of different induction methods on the biological functions of bone marrow-derived macrophages.  OBJECTIVE: To explore the effect of different induced polarization ways on biological behaviors of bone marrow-derived macrophages from rats. METHODS:  Rat bone marrow-derived macrophages were isolated and cultured in vitro, and identified by morphological observation, Wright Giemsa staining and flow cytometry. After being induced and activated by interferon-γ, lipopolysaccharide and interleukin-4 for 24 hours, the morphology of bone marrow-derived macrophages was observed by inverted microscope. The expression levels of cell surface markers Nos2 and Arg1 were detected by real time-PCR. CCK8 assay was performed to determine the proliferation ability of bone marrow-derived macrophages. Flow cytometry was performed to detect the apoptosis, and neutral red staining was performed to identify the phagocytic function of bone marrow-derived macrophages.     RESULTS AND CONCLUSION: Bone marrow-derived macrophages that stimulated by interferon-γ and lipopolysaccharide were highly expressing the cell surface marker Nos2 of M1, and apoptosis of bone marrow-derived macrophages can be slightly promoted as well as the phagocytic function of bone marrow-derived macrophages is reduced; while bone marrow-derived macrophages stimulated by interleukin-4 are highly expressing the cell surface marker Arg1 of M2. Cell proliferation and phagocytosis of bone marrow-derived macrophages are promoted, and apoptosis of bone marrow-derived macrophages is inhibited. The results confirm that the biological behavior of bone marrow-derived macrophages can be affected by different methods of induced polarization. Figures and Tables | References | Related Articles | Metrics

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Application status and prospect of induced pluripotent stem cell gene editing Zhou Can, Yang Linan, Yang Kun, Liu Qi 2021, 25 (25):  4038-4044.  doi: 10.12307/2021.017 Abstract ( 522 )   PDF (1515KB) ( 84 )   Save BACKGROUND: In recent years, due to advances in genetic engineering, cell reprogramming has become possible, and cell DNA can be manipulated by some tools, such as transgenes, transcriptional activator-like effector nucleases, zinc finger nucleases and CRISPR/Cas9. In the reprogramming of cells, the cells are first transformed into an induced pluripotent stem cell state, and then differentiated into the desired lineage, thereby generating a large number of reprogrammed cells. Since the advent of induced pluripotent stem cell technology ten years ago, stem cell biology and regenerative medicine have made tremendous progress. Human induced pluripotent stem cells are now widely used in disease modeling, drug development, and disease cell therapy. At the same time, clinical trials of induced pluripotent stem cell derivatives have also been initiated. With the continuous update of gene editing technology, the combination of induced pluripotent stem cell technology and gene editing, gene editing of disease induced pluripotent stem cells, correction of disease-causing mutations and use in cell therapy are becoming hotspots in translational medicine and regenerative medicine. OBJECTIVE: By summarizing the characteristics of induced pluripotent stem cells and their combined application with gene editing, the aim is to guide appropriate methods for the study of disease-causing mechanisms and treatment of disease. METHODS: The first author searched CNKI, China Biomedical Literature Database, Elsevier Database, PubMed Database for related literature from 2010 to 2020. In the title, abstract, and keyword, the search terms were “induced pluripotent stem cells, CRISPR/Cas9, genome editing, disease modeling, drug development, regeneration” in Chinese and English.  RESULTS AND CONCLUSION: Human induced pluripotent stem cells and CRISPR/Cas9 gene editing system are two tools for basic research and translational research, which can not only understand the molecular basis of many diseases, but also carry out pharmacological research. With the continuous development and progress of technology, induced pluripotent stem cells combined with gene editing have been carried out in many fields, and certain research results have been obtained. However, there are still shortcomings in this method. Off-target effects, high analysis costs, and gene editing with unknown pathogenic mutations or risk mutations, and the mutation risk of induced pluripotent stem cells implanted in the body need to be solved by scholars. Figures and Tables | References | Related Articles | Metrics

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Fate decision of mesenchymal stem cells in bone microenvironment Zhang Chunxi, Li Xiang, Zhou Yuxiang, Liu Zhen, Yang Yuquan, Jia Hao 2021, 25 (25):  4045-4052.  doi: 10.12307/2021.018 Abstract ( 506 )   PDF (988KB) ( 118 )   Save BACKGROUND: Bone marrow mesenchymal stem cells are a group of multipotent stem cells in bone marrow, which are the common progenitor cells of osteoblasts, adipocytes and chondrocytes. Both genetic information and external stimulation contribute to the balance of the differentiation of bone marrow mesenchymal stem cells. Its differentiation disorder is related to a variety of pathological processes, such as osteoporosis, obesity and aging. According to a 2018 survey by the National Health Commission of China, osteoporosis has become an important health problem for middle-aged and elderly people in China, with the prevalence of osteoporosis 6.0% in men and 32.1% in women aged over 50 years, and 51.6% in women aged over 65 years. OBJECTIVE: To summarize the regulation of the differentiation of bone marrow mesenchymal stem cells, to better understand the occurrence and development of osteoporosis and other diseases, so as to provide new ideas for their treatments.  METHODS: PubMed and CNKI databases were searched for the relevant articles from January 1997 to May 2020 with the search terms of “BMSCs, cell differentiation, osteoblasts, chondrocytes, adipocytes” in English and Chinese, respectively. After preliminary screening based on the inclusion and exclusion criteria, the articles with high relevance were included for review.   RESULTS AND CONCLUSION: Signaling pathways such as BMPs, Notch and WNT, transcription factors such as Runx2, C/EBP and PPARγ, non-coding RNA, hormones and mitochondria regulate the differentiation of bone marrow mesenchymal stem cells. Any abnormality may lead to pathological conditions. Bone marrow mesenchymal stem cells and their combination with new materials may provide new treatment for osteoporosis and other diseases. Figures and Tables | References | Related Articles | Metrics

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Significance and possibility of stem cells and multiple cell derived exosomes in the treatment of chronic respiratory diseases Yu Dan, Xu Guanglan, Zhao Mei, Li Jiao, Li Guosheng, Wang Guangyao, Lin Hao, Zheng Manli, Li Yuanling 2021, 25 (25):  4053-4057.  doi: 10.12307/2021.019 Abstract ( 495 )   PDF (630KB) ( 122 )   Save BACKGROUND: In recent years, with the in-depth study of exosomes, the protein RNA, DNA, miRNA and other molecular substances carried on the surface are closely related to the occurrence, development, and prognosis of chronic respiratory diseases. OBJECTIVE: Based on the structural and functional characteristics of exosomes, to explore the relationship between exosomes and chronic obstructive pulmonary disease, asthma, interstitial lung disease and lung cancer, and to systematically analyze the effects of exosomes from different cell sources on chronic respiratory diseases. METHODS: A review of the relevant literature of domestic well-known databases such as CNKI, Wanfang, VIP, CBM and foreign databases such as PubMed, Cochrane Library, and Embase in the past 10 years was reviewed. “Exosomes” and “respiratory diseases” were search terms in English and Chinese, and the search time was from the establishment of the database to May 2020. Relevant articles related to the treatment of respiratory diseases with exosomes were included.   RESULTS AND CONCLUSION: Exosomes carry a variety of active substances such as protein and RNA, and are widely involved in the information exchange between cells and tissues. Exosomes maintain the physiological functions of the active substances by virtue of their small diameter and difficulty in being swallowed, and exert many functions such as intercellular information transmission, immune regulation, inflammatory response and signal transduction, and have become potential targets for regulating the development of respiratory diseases. Exosomes improve the function of receptor cells, protect damaged tissues, and participate extensively in cellular inflammatory and immune response processes through their information transmission channels. They are expected to provide new treatment methods for the diagnosis and prevention of chronic respiratory diseases. Figures and Tables | References | Related Articles | Metrics

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Applicability of stem cells in the treatment of stress urinary incontinence Ren Tengzhou, Chen Jie, Zhao Wei, Chen Zhiwei, Zhang Teng, Wang Yan 2021, 25 (25):  4058-4064.  doi: 10.12307/2021.020 Abstract ( 471 )   PDF (629KB) ( 61 )   Save BACKGROUND: Stress urinary incontinence is one of the most common diseases of the lower urinary tract. Current treatment methods can only relieve symptoms, but cannot completely cure them. Regenerative medicine based on stem cells realizes the use of autologous cells, and its purpose is to treat the cause of urinary incontinence.  OBJECTIVE: To summarize the application of various types of stem cells in the treatment of female stress urinary incontinence in and outside China in recent years.  METHODS: Computer search of the CNKI, Wanfang, VIP, and PubMed databases from 2005 to 2020 was conducted. The search terms were “stem cells, stress urinary incontinence” in Chinese and English. Articles related to stem cells in the treatment of stress urinary incontinence were selected. The application of various types of stem cells in the treatment of stress urinary incontinence was summarized, organized, and discussed. RESULTS AND CONCLUSION: In all the studies on stem cell treatment of stress urinary incontinence, muscle derived stem cells and adipose derived stem cells are most used. They can support the regeneration of target tissues related to stress urinary incontinence patients. The main purpose is to restore its original function by treating the dysfunctional sphincter. Most studies have shown that stem cells have great potential in treating stress urinary incontinence. It is hoped that more basic research on stem cell treatment of stress urinary incontinence can be transformed into clinical applications, making stress urinary incontinence a disease that can be cured. Figures and Tables | References | Related Articles | Metrics

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Mesenchymal stem cells for the treatment of ulcerative colitis: possibility and feasibility Liang Yuan, Jiang Xiaoke, Bai Yangqiu, Luo Xiaoying, Zhang Bingyong 2021, 25 (25):  4065-4069.  doi: 10.12307/2021.021 Abstract ( 547 )   PDF (730KB) ( 132 )   Save BACKGROUND: Ulcerative colitis is a chronic nonspecific inflammatory disease of the intestine caused by immune disorders. As the course of disease prolongs, the incidence of canceration increases rapidly. In recent years, the incidence of ulcerative colitis has increased year by year, and the age of onset tends to be younger, but the traditional treatments have not been effective for some patients. Mesenchymal stem cells are a kind of cells with strong self-renewal, multi-directional differentiation, low immunogenicity and immune regulation. The studies relevant animal and clinic have shown that mesenchymal stem cells are safe and effective in treating ulcerative colitis, but most studies have smaller sample sizes. OBJECTIVE: To summarize the epidemiological characteristics and treatment status of ulcerative colitis, and to prospect the clinical application prospects of mesenchymal stem cells in the treatment of ulcerative colitis.  METHODS: We searched articles published in CNKI, Wanfang, PubMed and GreenMedical databases from January 2001 to April 2020 with the key words of “inflammatory bowel disease, ulcerative colitis, mesenchymal stem cells, inflammatory bowel disease, IBD, ulcerative colitis, UC, mesenchymal stem cells, MSCs”. A total of 115 articles were retrieved, and 42 articles were selected for summary. It includes experiments analysis, case analysis and review.  RESULTS AND CONCLUSION: The stem cells with homing, differentiation, and immune regulation have provided the possibility for the treatment of ulcerative colitis. Relevant animal experiments and clinical studies have shown that mesenchymal stem cells are safe and effective for ulcerative colitis, but the dosage and route of transplanted cells are still controversial. With the further research and clinical trials of mesenchymal stem cells in the treatment of ulcerative colitis, mesenchymal stem cell transplantation is expected to become a promising treatment for ulcerative colitis. Figures and Tables | References | Related Articles | Metrics

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Research, application and development of human amniotic epithelial cells in the field of obstetrics and gynecology Wang Xuan, Zhou Chao, Zhang Yingzi 2021, 25 (25):  4070-4075.  doi: 10.12307/2021.022 Abstract ( 465 )   PDF (646KB) ( 60 )   Save BACKGROUND: Human amniotic epithelial cells have a wide range of biological functions and can be used in the treatment of many diseases, such as conjunctival injury, burn, pulmonary fibrosis and heart disease. Human amniotic epithelial cells have been tested in the field of obstetrics and gynecology and achieved remarkable results, which is expected to become a new disease treatment, and is worthy of in-depth research and exploration. OBJECTIVE: To review the research progress, application status and development prospect of human amniotic epithelial cells on some diseases in the field of gynecology and obstetrics. METHODS: Key words “human amniotic epithelial cells”, “tumor” and “obstetrics and gynecology” were used to search PubMed and Web of Science databases, and Wanfang and CNKI Chinese databases were searched with key words “human amniotic epithelial cells”, “gynecological tumor” and “obstetrics and gynecology”. A total of 40 articles were included according to the inclusion and exclusion criteria. RESULTS AND CONCLUSION: (1) Human amniotic epithelial cells reverse abnormal vascular structure and function and induce apoptosis of endometrial carcinoma. (2) Human amniotic epithelial cells can inhibit apoptosis of granulosa cells induced by chemotherapy and restore fertility. (3) Human amniotic epithelial cells can treat uterine adhesion and improve fertility. (4) Human amniotic epithelial cells can treat recurrent spontaneous abortion. It is believed that with the further research, the function of human amniotic epithelial cells will be more widely developed and utilized. Figures and Tables | References | Related Articles | Metrics

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Autologous chondrocyte implantation in the treatment of cartilage defect of knee joint: no significant difference between regenerated and natural cartilages Li Xiang, Fu Peiliang 2021, 25 (25):  4076-4081.  doi: 10.12307/2021.023 Abstract ( 519 )   PDF (646KB) ( 133 )   Save BACKGROUND: With the improvement of the medical level and people’s higher requirements for the quality of life, the quality and requirements for cartilage repair in the clinic are getting more and more, but traditional repair methods cannot regenerate cartilage with good biological properties. OBJECTIVE: To review the research progress of autologous chondrocyte implantation in recent years, and to analyze its development process, basic science, indications, contraindications, surgical techniques, clinical efficacy and limitations, and look forward to the development trend of this field. METHODS: A computer-based online search of CNKI, PubMed, Web of Science databases, and Google Scholar was performed to retrieve papers published during 1990-2020 with the search terms “autologous chondrocyte implantation, cartilage defect, techniques, clinical effect, indications, contraindications, defect size, treatment after initial failure, return to sports, age, magnetic resonance imaging, limitation” in English and Chinese. The document types include treatise, reviews, case reports, and meta-analysis. A total of over 1 000 papers were retrieved, and 52 of them were included in the final analysis.  RESULTS AND CONCLUSION: Autologous chondrocyte transplantation first appeared for the treatment of knee cartilage defects in the late 1980s. The first generation of autologous chondrocyte transplantation used periosteal patches to seal the cultured chondrocytes in the defect. Due to the proliferation of periosteal grafts, second-generation autologous chondrocyte transplantation used collagen membrane patches instead of periosteal patches. The third generation of autologous chondrocyte transplantation used three-dimensional culture technology to improve cell delivery, allowing minimally invasive implantation, which could regenerate normal cartilage structure with accelerating patient recovery. Autologous chondrocyte transplantation was an effective method to treat high tibia or femoral cartilage defects, but it must solve the problems consisting of coronal force line, ligament laxity, and meniscus injury. Because of the graft needing a long time to mature, patients needed a specific rehabilitation plan to return to the sport, which assisted the injured patients in restoring strength and neuromuscular coordination as much as possible before the graft was fully mature.  Figures and Tables | References | Related Articles | Metrics

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Culture, research and application of patient-derived tumor organoids Feng Ziyi, Liang Shanshan, Yu Weiting, Wang Ruoyu 2021, 25 (25):  4082-4088.  doi: 10.12307/2021.024 Abstract ( 666 )   PDF (1132KB) ( 173 )   Save BACKGROUND: Tumor organoids provide the foundation for tumor biology research, screening and development of new tumor drugs, and precision individual medicine, with the advantages of high-throughput, high efficiency, and closer to the biological role of tumors in vivo. OBJECTIVE: This article systematically reviews the development and new progress of patient-derived tumor organoids, prospect the application direction and value of tumor organoids in the future, so as to provide the characteristic panorama of tumor organoids for researchers in related fields.  METHODS: In databases such as PubMed, Web of Science, Springer, and CNKI, the literature related to tumor organoids and patient-derived organoids was searched using the keywords of “Tumor/cancer organoids, Organoids, Cancer research, Three-dimensional culture, Cancer stem cell” in English and Chinese, respectively. Both clinical and basic researches were summarized from February 2017 to February 2020. RESULTS AND CONCLUSION: Tumor organoids can make up for the shortcomings of tumor research based on traditional cell lines, and are more reliable in the in vitro models for tumor research. According to different tumor types and patients’ own conditions, it is possible to select tumor cells from different sources to construct tumor organoids. Optimizing culture conditions by adding cytokines and biological materials is the key to tumor organoid culture. The patient-derived tumor organoids highly retain tumor heterogeneity, so that they can provide a more realistic and reliable platform for tumor biology research, new drug screening and precision medicine. However, patient-derived tumor organoids cannot fully reproduce the tumor microenvironment, such as lack of vascular support, nerve-humoral regulation, and immune cells function, so they cannot fully reflect changes in tumor progress, but co-culture and techniques can provide support for simulating the tumor microenvironment. Figures and Tables | References | Related Articles | Metrics

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Regulatory effect of exosomes on exercise-mediated insulin resistance diseases Chen Ziyang, Pu Rui, Deng Shuang, Yuan Lingyan 2021, 25 (25):  4089-4094.  doi: 10.12307/2021.025 Abstract ( 458 )   PDF (616KB) ( 217 )   Save BACKGROUND: Exosomes are closely related to insulin resistance diseases and play an important role in the diagnosis and treatment of insulin resistance diseases such as obesity and type 2 diabetes. In addition, exercise affects the biogenesis of the body fluid and the circulating exosomes, and mediates the role of intercellular communication. OBJECTIVE: To summarize the relationship between exosomes and insulin resistance diseases, and the role and mechanism of exercise-mediated exosomes in regulating insulin resistance related diseases. METHODS: The “extracellular vesicle, exosomes, insulin resistance, obesity, type 2 diabetes mellitus, exercise” were used as the key words. The literature related to PubMed and CNKI database from 1981 to 2020 was retrieved and 64 papers were selected according to inclusion and exclusion criteria.  RESULTS AND CONCLUSION: Exosomes are closely related to the occurrence and development of insulin resistance diseases, and can be used as biomarkers for the diagnosis of obesity and type 2 diabetes, inhibiting the development of obesity and type 2 diabetes by down-regulating the expression of obesity-related inflammatory factors and improving insulin sensitivity. Mediated by aerobic exercise and resistance exercise, exosomes from different cell sources regulate the regulation of their miRNA and protein expression in patients with extensive insulin resistance. Figures and Tables | References | Related Articles | Metrics

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Systematic review of the efficacy and safety of umbilical cord-derived cell transplantation for patients with cerebral palsy Zhong Liqing, Zhong Shanshan, Han Weichao, Hu Runkai, He Shufen, Ding Shaobo 2021, 25 (25):  4095-4100.  doi: 10.12307/2021.026 Abstract ( 310 )   PDF (1347KB) ( 109 )   Save OBJECTIVE: In recent years, umbilical cord-derived cells transplantation is considered to be one of the promising strategies for the treatment of cerebral palsy. However, clinical evidence is still limited and there is controversy regarding the clinical efficacy of stem cells in the treatment of cerebral palsy. This article systematically evaluated the efficacy and safety of umbilical cord-derived cells transplantation in the treatment of patients with cerebral palsy. METHODS: Randomized controlled trials of umbilical cord-derived cell transplantation in patients with cerebral palsy were systematically searched, from the inception of the database to August 2020, including the Cochrane Library, PubMed, Embase, CNKI, Wanfang Database, and China Clinical Trial Registration Center. We used Cochrane’s risk of bias assessment for the quality of the included studies. Two reviewers conducted independent quality evaluations for the included studies. After data extraction, RevMan 5.0 software was used for meta-analysis of outcome indicators.  RESULTS: (1) There are six randomized controlled trials regarding umbilical cord-derived cells transplantation for the treatment of cerebral palsy. Literature quality was medium. (2) The results of meta-analysis showed that umbilical cord-derived cell therapy could significantly improve the gross motor function measurement score (SMD=0.83, 95%CI=0.36-1.30, P=0.000 6) and the gross motor performance measurement score (SMD=0.51, 95%CI=0.22-0.80, P=0.000 5). (3) In the subgroup analysis, the results showed that after umbilical cord-derived cell treatment, the gross motor function measurement scores of patients with cerebral palsy increased significantly at 6 months (SMD=0.91, 95%CI=0.07-1.74, P=0.03). (4) There was no statistical difference in adverse events such as upper respiratory tract infection, diarrhea and constipation between the two groups. CONCLUSION: Umbilical cord-derived cell transplantation could significantly improve motor function in patients with cerebral palsy, and the safety was good. However, due to the small number of included literature, large-sample, multi-center, and high-quality clinical randomized controlled trials are still needed for further verification. Figures and Tables | References | Related Articles | Metrics