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    08 July 2020, Volume 24 Issue 19 Previous Issue    Next Issue
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    Activity of intervertebral disc stem cells and nucleus pulposus mesenchymal stem cells in intervertebral disc niche condition 
    Hu Wei, Tong Min, Yang Tao, Xiong Wei, Huang Yifei
    2020, 24 (19):  2953-2958.  doi: 10.3969/j.issn.2095-4344.2041
    Abstract ( 335 )   PDF (670KB) ( 73 )   Save

    BACKGROUND: Disc microenvironment plays an important role in the biological behavior of stem cells. It is proposed that the microenvironment can be used to achieve the repair of disc tissue independent of seed cells by niche regulation.

    OBJECTIVE: To explore the difference in the activity of intervertebral disc stem cells and nucleus pulposus mesenchymal stem cells under the intervertebral disc niche.

    METHODS: Ten healthy male Sprague-Dawley rats were used. The intervertebral disc bone tissue was isolated according to the anatomical area. Intervertebral disc stem cells were digested with type II collagenase and cultured in vitro. Nucleus pulposus was isolated, and nucleus pulposus mesenchymal stem cells were cultured in vitro using enzyme digestion. Intervertebral disc stem cells and nucleus pulposus mesenchymal stem cells were cultured and amplified in normal condition and intervertebral disc niche. The proliferation curves of cultured cells were measured by MTT method at 1-6 days after culture. The expression level of CD29 was detected by flow cytometry at 1, 3 and 6 days.

    RESULTS AND CONCLUSION: Under different culture conditions, the proliferation of intervertebral disc stem cells and nucleus pulposus mesenchymal stem cells showed an opposite trend. Under normal culture conditions, intervertebral disc stem cells and nucleus pulposus mesenchymal stem cells were proliferated logarithmically from day 4 to day 6, with no statistical significance (P > 0.05). In the intervertebral disc niche condition, the survival rate of nucleus pulposus mesenchymal stem cells was significantly lower than that of intervertebral disc stem cells (P < 0.05). In intervertebral disc niche condition, at 3 and 6 days, the surface positive antigen CD29 of intervertebral disc stem cells was significantly higher than that of nucleus pulposus mesenchymal stem cells (P < 0.05). These results suggest that in the intervertebral disc niche condition, the activity of intervertebral disc stem cells and nucleus pulposus mesenchymal stem cells is inhibited to some extent, but intervertebral disc stem cells are more active than nucleus pulposus mesenchymal stem cells. 

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    Expression of tissue transgiutaminase 2 in differentiation of nasal mucosal mesenchymal stem cells
    Lü Demin, Shi Wentao, Lu Hao, Bi Shiqi, Yang Kaiyuan, Cui Xuewen, Zhang Zhijian
    2020, 24 (19):  2959-2964.  doi: 10.3969/j.issn.2095-4344.2025
    Abstract ( 427 )   PDF (779KB) ( 91 )   Save

    BACKGROUND: Ectodermal mesenchymal stem cells can differentiate into other types of cells in a specific external environment. The expression of some specific proteins during differentiation may directly affect the direction of their fate.

    OBJECTIVE: To investigate the expression of tissue transgiutaminase 2 in rat nasal mucosal mesenchymal stem cells during osteoblast differentiation and neuron-like differentiation.

    METHODS: Rat nasal mucosal mesenchymal stem cells were isolated and cultured by tissue adherence method, and differentiated into neuroblast-like cells and osteoblasts. Immunofluorescence was used to detect the expression of neuro-related proteins GAP-43, TUBB3 and bone-associated proteins OCN and COLI at different time points. Western blot assay was used to detect neuro-related proteins GAP-43, TUBB3, bone-associated protein OCN and COLI, neurotrophic factor NT-3, BDNF, extracellular matrix FN, LN, and tissue transgiutaminase 2.

    RESULTS AND CONCLUSION: (1) After 3 days of neurogenic induction, immunofluorescence showed that GAP-43 and TUBB3 expressed positively. At 7 days after osteogenic induction, COLI and OCN were positive under immunofluorescence staining. (2) At 3, 5, 7 days after neurogenic induction, the expression levels of nerve cell-associated proteins GAP-43, TUBB3 and tissue transgiutaminase 2 were increased with time detected by western blot assay. At 7 and 14 days after osteogenic induction, the levels of osteoblast-associated proteins COLI, OCN and tissue transgiutaminase 2 were increased with time. (3) At 7 days after neurogenic induction, western blot assay showed that the levels of NT-3, BDNF and tissue transgiutaminase 2 were higher than those in the non-induction group. At 14 days after osteogenic induction, the expression levels of FN, LN and tissue transgiutaminase 2 in the extracellular matrix were higher than those in the non-induction group. (4) To conclude, tissue transgiutaminase 2 may regulate the differentiation of nasal mucosal mesenchymal stem cells into neuron-like cells and osteoblasts.

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    GATA-4-overexpressed bone marrow mesenchymal stem cell secreted exosomes promote bone marrow mesenchymal stem cell differentiation into cardiomyocyte-like cells
    He Jigang, Wang Zihao, Xie Qiaoli, Li Hongrong, Yan Dan, Li Yongwu
    2020, 24 (19):  2965-2971.  doi: 10.3969/j.issn.2095-4344.2056
    Abstract ( 435 )   PDF (1015KB) ( 65 )   Save

    BACKGROUND: Preliminary study has shown that overexpression of GATA-4-overexpressing bone marrow mesenchymal stem cell (BMSCs) exosomes (BMSCsGATA-4-exosome) can promote BMSCs differentiate into cardiomyocytes, indicating it can repair myocardial infarction. Additionally, high expression of miRNA-673-5p is observed in miRNA-673-5p BMSCsGATA-4-exosome and focal myocardium of myocardial infarction, which involve in cell differentiation, suggesting that miRNA-673-5p may be a key molecular of BMSCsGATA-4-exosome for repairing myocardial infarction.

    OBJECTIVE: To investigate the molecular regulatory network of BMSCsGATA-4-exosomes that promotes BMSCs differentiation into cardiomyocyte-like cells.

    METHODS: miR-673-5p-mimic was added to the BMSCs culture system as an experimental group (BMSCsmiR-330-3p-mimic). BMSCsGATA-4, BMSCsGATA-4-empty vector, BMSCs and BMSCsGATA-4-miR-673-5p-inhibitor groups were set as confounding factor control groups. The exosomes and myocardial cells secreted by each group were co-cultured for 24 hours. The expression levels of myocardium specific molecules α-actin, Desmin, cTnT and Cx43 were detected by immunofluorescence and RT-PCR. The expression levels of the corresponding miRNA-673-5p target genes TSC-1, ERK1/2 and Mef2c were detected through western blot assay based on the prediction results of the microRNA target gene.

    RESULTS AND CONCLUSION: The BMSCsmiR-673-5p-mimic-exosome+BMSCs culture group had the highest α-actin, Desmin, cTnT and Cx43 levels (P < 0.05), and the lowest TSC-1 expression (P < 0.05). In summary, BMSCsGATA-4-exosome inhibits the expression of TSC-1 via miRNA-673-5p to promote BMSCs differentiation into cardiomyocyte-like cells.

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    Effects of umbilical cord blood-derived mesenchymal stem cell transplantation on recovery of nerve function and telomerase reverse transcriptase expression in brain tissue of cerebral infarction rats 
    Yu Heng, Zhou Tao
    2020, 24 (19):  2972-2977.  doi: 10.3969/j.issn.2095-4344.2057
    Abstract ( 340 )   PDF (1058KB) ( 84 )   Save

    BACKGROUND: Umbilical cord blood-derived mesenchymal stem cells can penetrate the ependyma into the brain tissue via the systemic circulation, migrate into the injury area and differentiate into neurons. They are as substitute cells applied in the treatment of central nervous system diseases

    OBJECTIVE: To explore the effects of umbilical cord blood-derived mesenchymal stem cell transplantation on the functional recovery of nerve and expression of telomerase reverse transcriptase in the brain tissue of cerebral infarction rats.

    METHODS: One hundred and thirty rats were enrolled and were randomly divided into control group (n=30), model group (n=30), umbilical cord blood-derived mesenchymal stem cell 1 group (n=35) and umbilical cord blood-derived mesenchymal stem cell 2 group (n=35). The control group was not given any treatment. The rat models of cerebral infarction were made by internal carotid artery suture method in the other groups. At 1 and 4 days after successful modeling, 2×106 umbilical cord blood-derived mesenchymal stem cells were transplanted into tail vein in the umbilical cord blood-derived mesenchymal stem cell 1 and 2 groups. The levels of reactive oxygen species and superoxide dismutase were detected at 24 hours after transplantation. The nerve function score was detected by Y-maze test at 7 and 14 days after transplantation. The neuronal apoptosis in the center of lesions was detected by TUNEL assay. The expression levels of Caspase-3, Bax, Bcl-2 and telomerase reverse transcriptase proteins around the infarct lesion were detected by western blot assay. The mRNA expression of telomerase reverse transcriptase around infarct lesions was detected by RT-PCR.

    RESULTS AND CONCLUSION: Compared with the control group, in the model group, the error number in the Y-maze test, nerve function scores, apoptotic index, expression levels of Caspase-3 and Bax, and level of reactive oxygen species were significantly increased (P < 0.05), the expression of Bcl-2 and telomerase reverse transcriptase protein and mRNA, and level of superoxide dismutase were significantly decreased (P < 0.05). Compared with the model group, in the umbilical cord blood-derived mesenchymal stem cell 1 and 2 groups, the error number in the Y-maze test, nerve function score, apoptotic index, expression of Caspase-3 and Bax, and level of reactive oxygen species were significantly decreased (P < 0.05), while the expression of Bcl-2 and telomerase reverse transcriptase protein and mRNA and level of superoxide dismutase were significantly increased (P < 0.05). Compared with the umbilical cord blood-derived mesenchymal stem cell 2 group, in the umbilical cord blood-derived mesenchymal stem cell 1 group, the error number in the Y-maze test, nerve function score, apoptotic index, expression of Caspase-3 and Bax, and level of reactive oxygen species were significantly decreased (P < 0.05), while the expression of Bcl-2 and telomerase reverse transcriptase protein and mRNA and level of superoxide dismutase were significantly increased (P < 0.05). These findings indicate that umbilical cord blood-derived mesenchymal stem cell transplantation can effectively promote the neurological recovery in rats with cerebral infarction, and up-regulate the expression of telomerase reverse transcriptase in rat brain tissue. Moreover, earlier cell transplantation indicates better effects.

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    miRNA-148a promotes the differentiation of human induced pluripotent stem cells into cardiomyocyte-like cells 
    Mao Qing, Pang Yiheng, Lu Yongxiang, Liang Xiulin
    2020, 24 (19):  2978-2984.  doi: 10.3969/j.issn.2095-4344.2047
    Abstract ( 384 )   PDF (813KB) ( 69 )   Save

    BACKGROUND: Studies have shown that miRNA-148a can promote human bone marrow mesenchymal stem cells to differentiate into mature cardiomyocyte-like cells, but the effect of miRNA-148a on the differentiation of human induced pluripotent stem cells into cardiomyocyte-like cells has not been reported.

    OBJECTIVE: To investigate the effect of miRNA-148a on the differentiation of human induced pluripotent stem cells into cardiomyocyte-like cells.

    METHODS: Human induced pluripotent stem cells differentiating into cardiomyocyte-like cells were divided into three groups. Cells in the control group were not treated. Cells in the low expression group were treated with miRNA-148a for 28 days, and those in the high expression group were treated with mimics of miRNA-148a for 28 days. In addition, human induced pluripotent stem cells cultured for 28 days were taken as the blank control group. CCK-8 was used to detect cell proliferation activity. qRT-PCR was used to detect the expression of miRNA-148a. Immunofluorescence staining and western blot analysis were performed to detect the expression of MHC and cTnT protein.

    RESULTS AND CONCLUSION: The expression of intracellular miR-148a mRNA and cell proliferation activity in the low expression group were lower than those in the blank control and control groups, while those in the high expression group were significantly higher than those in the other three groups (P < 0.01). There were no positive expression of MHC and cTnT in the blank control group. There were positive expressions of MHC and cTnT in the control, low expression and high expression groups. The expression of MHC and cTnT protein in the low expression group was significantly lower than that in the control group, and that in the high expression group was significantly higher than that in the other three groups (P < 0.01). These results suggest that miRNA-148a can promote the differentiation of human induced pluripotent stem cells into cardiomyocyte-like cells.

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    Zinc ion concentration affects proliferation and osteogenic differentiation of rabbit bone marrow mesenchymal stem cells 
    Zhao Qiao, Yang Fei, Zhang Chengdong, Chen Shuo, Sun Xiao, Zhang Bo, Xiao Dongqin, Liu Kang, Feng Gang, Duan Ke
    2020, 24 (19):  2985-2990.  doi: 10.3969/j.issn.2095-4344.2042
    Abstract ( 463 )   PDF (862KB) ( 130 )   Save

    BACKGROUND: Zinc ion is a necessary metal trace element in human body, which plays an important role in inhibiting osteoclast activity and promoting osteogenic differentiation. However, the effect of zinc ion at different concentrations on osteogenic differentiation of rabbit bone marrow mesenchymal stem cells has been rarely studied.

    OBJECTIVE: To evaluate the effects of zinc ion at different concentrations on the proliferation and osteogenic differentiation of rabbit bone marrow mesenchymal stem cells for exploring the appropriate zinc ion concentration.  

    METHODS: Bone marrow mesenchymal stem cells were extracted from the long bone marrow of rabbits and passaged. The cells were divided into six groups, including 10-4, 10-5, 10-6, 10-7 and 10-8 mol/L zinc ion groups, and blank control group. The cell proliferation activity was measured by Cell Counting Kit-8 and the growth curve was drawn. Alkaline Phosphatase Assay kit was used to evaluate the osteogenic differentiation ability of the cells, and the growth activity of the cells was shown by Live-Dead Cell Staining Kit. The mineralization ability of the cells was observed by alizarin red S staining. The expression of osteogenic genes was detected by fluorescence quantitative polymerase chain reaction.

    RESULTS AND CONCLUSION: The number of cells in each group showed an increasing trend with the prolongation of time except for the 10-4 mol/L zinc ion group. After 5 days of culture, the number of cells was highest in the 10-7 mol/L zinc ion group, but lowest in the 10-4 mol/L zinc ion group. Alkaline phosphatase activity was highest when zinc ion concentration was 10-7 mol/L, but lowest at the 10-4 mol/L zinc ion after cell culture for 14 days. The method of Live-Dead Cell Staining revealed the number of viable cells was highest in the 10-7 mol/L zinc ion group. All cells were almost dead in the 10-4 mol/L zinc ion group. Calcium nodule formation was visible, and the expression level of osteogenic genes was highest in the 10-7 mol/L zinc ion group after 14 days of cell culture. These findings suggest that zinc ion can effectively promote the proliferation and osteogenic differentiation of rabbit bone marrow mesenchymal stem cells in a certain concentration range. The promoting effects of zinc ion on proliferation, osteogenic induction and mineralization are strongest. Therefore, the addition of a suitable concentration of zinc ions in the medium is beneficial for the osteogenic differentiation of rabbit bone marrow mesenchymal stem cells.

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    MicroRNA-141 is regulated by serum of velvet antler to promote the proliferation of bone marrow mesenchymal stem cells in dexamethasone-induced cell model 
    Meng Chenyang, Xue Fei, Jia Yanfei, Tong Yanxiang, Zhang Lifeng, Yu Chengyong, Zhang Zhehan, Wang Wenxuan, Hao Ting, Feng Wei
    2020, 24 (19):  2991-2996.  doi: 10.3969/j.issn.2095-4344.2079
    Abstract ( 402 )   PDF (766KB) ( 50 )   Save

    BACKGROUND: The proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) can delay the procession of steroid-induced femoral head necrosis. Besides, microRNA-141 (miR-141) is one of the important regulatory factors to promote cell proliferation. In addition, velvet antler is a traditional Chinese medicine which has significant roles in repairing bone and tissue and improving health.

    OBJECTIVE: To investigate whether velvet antler serum can regulate the expression of miR-141 to promote the proliferation of BMSCs, and further delay or reverse the progression of steroid-induced femoral head necrosis.

    METHODS: BMSCs were isolated and cultured from Sprague-Dawley rats. The passage 3 BMSCs were transfected with miR-141 mimic or miR-141 inhibitors, and then real-time PCR and methyl thiazolyl tetrazolium (MTT) assay were performed for detecting miR-141 expression and cell proliferation, respectively. The passage 3 BMSCs were divided into three groups: control group (α-MEM), dexamethasone group (α-MEM+1 μmol/L dexamethasone), and velvet antler serum group (α-MEM+1 μmol/L dexamethasone+15% velvet antler serum). Expression of miR-141 mRNA was detected by real-time PCR at 24 hours after intervention. The proliferation ability of BMSCs was evaluated by MTT assay at 24, 48, and 72 hours after intervention.

    RESULTS AND CONCLUSION: After transfection with miR-141 mimic, the expression of miR-141 mRNA was upregulated, while the cell proliferation was reduced. After transfection with miR-141 inhibitor, the expression of miR-141 mRNA was downregulated, while the cell proliferation was increased. The expression of miR-141 mRNA was significantly higher in the dexamethasone group than the control group (P < 0.01), while the treatment with velvet antler serum could significantly downregulate the expression of miR-141 mRNA (P < 0.01). The absorbance of BMSCs in the dexamethasone group was significantly lower than that in the control group (P < 0.01), and the absorbance value in the velvet antler serum group was significantly higher than that in the dexamethasone group (P < 0.01). In conclusion, the serum containing velvet antler can downregulate the expression of miR-141 which is upregulated by dexamethasone and then do help to promote the proliferation of BMSCs.

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    Application potential of CD146 positive subpopulation as seed cells for cartilage tissue engineering
    Sui Xiang, Tian Guangzhao, Yang Zhen, Li Xu, Liu Shuyun, Guo Quanyi
    2020, 24 (19):  2997-3003.  doi: 10.3969/j.issn.2095-4344.2033
    Abstract ( 438 )   PDF (888KB) ( 73 )   Save

    BACKGROUND: The development of regenerative medicine and the appearance of tissue engineering technology provide a new solution for cartilage defect reconstruction. In tissue engineering, mesenchymal stem cells are widely used seed cells. However, as a heterogeneous cell group, stem cells play different roles in different subsets. Therefore, the application of key functional subsets of mesenchymal stem cells in cartilage repair has a broad application prospect.

    OBJECTIVE: To sort CD146 positive subpopulation cells from human adipose-derived mesenchymal stem cells to verify their biological characteristics and potential as seed cells in cartilage tissue engineering.

    METHODS: Human adipose-derived mesenchymal stem cells were provided by Zhejiang Jinshidai Biotechnology Co., Ltd. Surface markers of human adipose-derived mesenchymal stem cells were identified by flow cytometry. CD146 positive subpopulation cells were sorted from human adipose-derived mesenchymal stem cells using magnetic-activated cell sorting. Molecular characteristics of two kinds of cells were analyzed by gene chip detection technology and bioinformatics analysis technology. Two kinds of cells were induced to chondrocytes in vitro and histologically examined. Cell viability and apoptosis of two kinds of cells were detected before and after cryopreservation.

    RESULTS AND CONCLUSION: Human adipose-derived mesenchymal stem cells highly expressed stem cell-associated markers CD73 and CD90, but did not express hematopoietic stem cell-associated markers CD34, CD45, and HLA-DR. Bioinformatics analysis results showed that CD146 positive subpopulation had different functions in inflammatory pathways and musculoskeletal diseases compared with human adipose-derived mesenchymal stem cells. CD146 positive subpopulation could differentiate into cartilage, and its chondrogenic differentiation ability was better than that of human adipose-derived mesenchymal stem cells. CD146 positive subpopulation had better apoptosis and activity than human adipose-derived mesenchymal stem cells after resuscitation. These results suggest that CD146 positive subpopulation has good chondrogenic differentiation potential and is a promising seed cell for cartilage tissue engineering. 

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    The role of PI3K/Akt pathway in hypoxia-induced cell proliferation and endothelial cell differentiation of adipose-derived stem cells
    Yin Lingni, Chen Dexuan
    2020, 24 (19):  3004-3009.  doi: 10.3969/j.issn.2095-4344.2038
    Abstract ( 509 )   PDF (756KB) ( 45 )   Save

    BACKGROUND: A large number of studies have confirmed that hypoxia can promote the proliferation and differentiation of stem cells, but the pathway by which it plays its role remains unclear.

    OBJECTIVE: To investigate the effects of hypoxia on the proliferation of adipose-derived stem cells and their differentiation into endothelial cells and investigate the role of PI3K/Akt pathway in this process.

    METHODS: Passage 3 adipose-derived stem cells of Wistar rats were divided into three groups according to the different culture conditions: normoxia group, hypoxia group, and hypoxia+LY294002 group. Three groups of cells were cultured for 24 hours in an incubator containing 20% O2. Cells in the hypoxia group were cultured in an incubator containing 2% O2, and those in the normoxia group were still cultured in an incubator containing 2% O2. Cells in the hypoxia+LY294002 group were cultured in medium supplemented with 25 mmol/L PI3K/Akt pathway inhibitor LY294002 under the hypoxic culture conduction. After 24 hours of culture, p-Akt expression was detected by Western blot assay to indicate the activation of PI3K/Akt pathway. The proliferation of adipose-derived stem cells was measured by CCK-8 method. Three groups of adipose-derived stem cells were induced to differentiate into vascular endothelial cells for 10 days. The differentiation of adipose-derived stem cells into endothelial cells was detected by qRT-PCR and anti-CD31 immunofluorescence staining.

    RESULTS AND CONCLUSION: Adipose-derived stem cells at passage 3 exhibited elongated fibroblast-like morphology. Cytometry analysis showed most of adipose-derived stem cells at passage 3 were negative for CD 34 and CD45 and positive for CD105 and could be induced towards osteogenic and adipogenic differentiation. The expression of p-Akt was significantly increased after hypoxic culture, which was inhibited obviously after adding LY294002. CCK-8 showed that the proliferation of adipose-derived stem cells in the hypoxia group was significantly higher than that in the normoxia group and hypoxia+LY294002 group (P < 0.05). The proliferation of adipose-derived stem cells in the hypoxia+LY294002 group was significantly lower than that in the hypoxia group (P < 0.05). The results of qRT-PCR and anti-CD31 immunofluorescence staining showed that the expression of endothelial cell gene and specific protein CD31 in the hypoxia group was significantly higher than that in the normoxia and hypoxia+LY294002 groups (P < 0.05). The expression of CD31 in the hypoxia+LY294002 group was significantly lower than that in the hypoxia group (P < 0.05), but it was significantly higher than that in the normoxia group (P < 0.05). These results suggest that the PI3K/Akt pathway plays an important role in hypoxia-induced cell proliferation and vascular endothelial cell differentiation of adipose-derived stem cells.

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    Urine-derived stem cells differentiate into urothelial cells and smooth muscle cells in vitro
    Zhu Haizhou, Zhao Zhankui, Wang Xinzhe, Liu Deqian, Yu Honglian
    2020, 24 (19):  3010-3016.  doi: 10.3969/j.issn.2095-4344.2070
    Abstract ( 436 )   PDF (927KB) ( 61 )   Save

    BACKGROUND: Adult stem cells are pluripotent stem cells that exist in differentiated tissues. Urine-derived stem cells are newly discovered adult stem cells. They have attracted increasing attentions in the tissue engineering, due to its advantages of convenient sampling, highly proliferative ability and multidirectional differentiation potential.

    OBJECTIVE: To investigate the separation and extraction method of urine-derived stem cells and to investigate the feasibility of differentiation into urothelial cells and smooth muscle cells in vitro.

    METHODS: Urine specimens were collected from healthy adults, and urine-derived stem cells were obtained by isolation and culture in vitro. Cell counting kit-8 assay was used to detect cell proliferation and plot cell growth curve. Cell phenotype was detected by flow cytometry. The differentiation into urothelial and smooth muscle cells was induced by special medium respectively in vitro. The cell differentiation was detected by quantitative PCR, immunohistochemical staining, immunofluorescence cell staining and western blot assay.

    RESULTS AND CONCLUSION: Urine-derived stem cells were successfully isolated from the urine specimens of healthy adults. Urine-derived stem cells possessed high proliferation rate and the cell growth curve exhibited an S-shape. Urine-derived stem cells exhibited high expression of CD29 (98.11%) and CD90 (95.74%), both of which are mesenchymal stem cell surface markers. After 14 days of induction in vitro, urine-derived stem cells were able to express urothelial cell specific genes Cytokeratin 7, Cytokeratin 20, Uroplakin II and smooth muscle cell specific genes α-SMA and SM22. These results suggest that urine-derived stem cells can differentiate into urothelial cells and smooth muscle cells after induction in vitro and can be used as ideal seed cells for urinary tract tissue engineering.

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    Mechanism underlying basic fibroblast growth factor and insulin-like growth factor-1 effects on proliferation and apoptosis of spermatogonial stem cells
    Li Hong, Wu Shaohua, Qiu Mingxing, Deng Qingfu, Lei Guolin, Li Qinglong
    2020, 24 (19):  3017-3022.  doi: 10.3969/j.issn.2095-4344.2066
    Abstract ( 450 )   PDF (820KB) ( 137 )   Save

    BACKGROUND: As a necessary regulatory factor of in vitro cell culture, and in vivo cell growth and proliferation, growth factors have attracted much attention.

    OBJECTIVE: To investigate the effects of basic fibroblast growth factor (bFGF) combined with insulin-like growth factor-1 (IGF-1) on the proliferation and apoptosis of spermatogonial stem cells in mice.

    METHODS: Spermatogonial stem cells were isolated and cultured from the testis of 6-8 days old male Kunming mice and were identified. Spermatogonial stem cells were inoculated into the feeder layer of embryonic fibroblasts treated with mitomycin C, and were then divided into four groups. Control group was cultured with normal DMEM medium; bFGF and IGF-1 groups were cultured with DMEM medium containing

    20 μg/L bFGF and 20 μg/L IGF-1, respectively; bFGF+IGF-1 group was cultured with DMEM medium containing 20 μg/L bFGF and 20 μg/L IGF-1. The proliferation activity of spermatogonial stem cells was detected by cell counting kit-8 assay and EDU staining. The growth cycle and apoptosis of spermatogonial stem cells were detected by flow cytometry. The expression levels of PCNA, Bax and Bcl-2 proteins were detected by western blot assay.

    RESULTS AND CONCLUSION: Compared with the control group, the absorbance values in the bFGF, IGF-1 and bFGF+IGF-1 groups were significantly increased. Compared with the bFGF and IGF-1 groups, the absorbance values in the bFGF+IGF-1 group were further increased (P < 0.05). EDU staining results showed the same conclusion as cell counting kit-8 assay results. The proportion of S+G2/M phase cells in the bFGF+IGF-1 group was significantly higher than that in the other three groups (P < 0.05). The proportion in the IGF-1 and bFGF groups was significantly higher than that in control group (P < 0.05). Compared with the control group, the number of apoptotic cells in the bFGF, IGF-1 and bFGF+IGF-1 groups was decreased. Compared with the bFGF and IGF-1 groups, the number of apoptotic cells in the bFGF+IGF-1 group was further decreased. Compared with the control group, the relative expression levels of Bax protein in the bFGF, IGF-1 and bFGF+IGF-1 groups were significantly decreased (P < 0.01), and the expression levels of Bcl-2 and PCNA proteins were significantly increased (P < 0.05). Compared with the bFGF and IGF-1 groups, the relative expression level of Bax protein in the bFGF + IGF-1 group was decreased further (P < 0.01), and the relative expression levels of Bcl-2 and PCNA proteins were increased further (P < 0.05). These results indicate that bFGF and IGF-1 can promote cell proliferation and inhibit cell apoptosis by up-regulating the expression of PCNA and Bcl-2 proteins and down-regulating the expression of Bax protein. The combination of bFGF and IGF-1 can achieve favorable effects.

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    Heat-shock endothelial cells induce differentiation of bone marrow mesenchymal stem cells into vascular endothelial cells
    Cao Baichuan, Zeng Gaofeng, Gao Yunbing, Deng Guiying, Cen Zhongxi, Zhang Chuanyang, Guo Yande, Zong Shaohui
    2020, 24 (19):  3023-3028.  doi: 10.3969/j.issn.2095-4344.2081
    Abstract ( 327 )   PDF (1095KB) ( 145 )   Save

    BACKGROUND: Current research on the differentiation of mesenchymal stem cells into endothelial cells mainly focuses on the induction of cytokines or co-culture of two types of cells. Research has been not yet reported on heat shock-treated endothelial cells inducing the differentiation of mesenchymal stem cells into endothelial cells.

    OBJECTIVE: To investigate the ability of heat shock-treated endothelial cells to induce bone marrow mesenchymal stem cells to differentiate into vascular endothelial cells, and to explore the angiogenic capacity of induced bone marrow mesenchymal stem cells.

    METHODS: Human bone marrow mesenchymal stem cells were co-cultured with heat shock-treated human umbilical vein endothelial cells in a non-contact manner. The expression of CD31, CD144, VEGFR2 and vWF in the bone marrow mesenchymal stem cells was detected by flow cytometry at 14 days after co-culture. The immunofluorescence of the cells was further verified. In vivo angiogenesis test was detected using hematoxylin-eosin staining in nude mice undergoing subcutaneous transplantation of induced and non-induced bone marrow mesenchymal stem cells. Matrigel angiogenesis test was applied to observe the angiogenic ability of induced and non-induced bone marrow mesenchymal stem cells.

    RESULTS AND CONCLUSION: After coculture, bone marrow mesenchymal stem cells had paving-stone like structure. Flow cytometry and cellular immunofluorescence results showed an increase in the expression of VEGFR2, vWF, CD31 and CD144 after co-culture. The hematoxylin-eosin staining of the graft showed that the induced bone marrow mesenchymal stem cells arranged in a regular manner and had an angiogenic tendency. The Matrigel angiogenesis test showed that the angiogenic ability of bone marrow mesenchymal stem cells was increased after induction compared with the control group. These findings indicate that co-culture with heat shock-treated human umbilical vein endothelial cells can promote the differentiation of mesenchymal stem cells into endothelial cells, and the specific phenotype of endothelial cells is obviously transformed, which has a certain tendency of angiogenesis.

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    S100A4 promotes differentiation of neural stem cells through up-regulation of brain-derived neurotrophic factor
    Du Xiaowen, Lin Dapeng, Tu Guanjun
    2020, 24 (19):  3029-3034.  doi: 10.3969/j.issn.2095-4344.2076
    Abstract ( 345 )   PDF (764KB) ( 88 )   Save

    BACKGROUND: How to promote neural stem cells differentiate into neurons is a difficulty. S100A4 has been found to play a role in the nervous system repair by various pathways.

    OBJECTIVE: To investigate whether S100A4 affects the differentiation of neural stem cells into neurons through up-regulating the expression of brain-derived neurotrophic facto.

    METHODS: The neural stem cells from brain hippocampus and subependymal region of embryonic mice were cultured in vitro and passaged. The S100A4 expression vector and/or brain-derived neurotrophic factor + siRNA were transfected into neural stem cells by electroporation, and the cells were induced to differentiate into neurons at 48 hours after transfection. Three days later, the expression levels of brain-derived neurotrophic factor and Tuj1 in cells were detected by western blot assay. Proportion of Tuj1 positive neurons was tested by immunofluorescence.

    RESULTS AND CONCLUSION: Compared with the unrelated sequence plasmid group, the proportion of Tuj1 positive neurons and the expression levels of Tuj1 and brain-derived neurotrophic factor in the S100A4 transfection group were significantly increased (P < 0.01). Compared with the S100A4+siRNA unrelated sequence plasmid group, the proportion of Tuj1 positive neurons and the expression levels of Tuj1 and brain-derived neurotrophic factor in the co-transfection group were significantly decreased (P < 0.01). These results indicate that S100A4 overexpression can promote the differentiation of neural stem cells into neurons, which may be mediated by brain-derived neurotrophic factor.

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    Cell culture supernatant of olfactory ensheathing cells promotes nerve regeneration after peripheral nerve injury in rats
    Yang Yujie, Xia Bing, Gao Jianbo, Li Shengyou, Ma Teng, Huang Jinghui, Luo Zhuojing
    2020, 24 (19):  3035-3041.  doi: 10.3969/j.issn.2095-4344.2067
    Abstract ( 391 )   PDF (855KB) ( 221 )   Save

    BACKGROUND: Previous studies have found that the culture supernatant of the olfactory ensheathing cells is capable of promoting axonal regeneration and functional recovery after spinal cord injury, but there is a lack of research in the field of peripheral nerve.

    OBJECTIVE: To investigate whether olfactory ensheathing cell culture supernatant is beneficial for nerve repair after peripheral nerve injury.

    METHODS: Olfactory ensheathing cells were isolated and purified, to prepare the supernatant. The olfactory ensheathing cell culture supernatant was applied to the dorsal root ganglion tissue block in vitro to observe the axon growth of the dorsal root ganglion. The olfactory ensheathing cell culture supernatant was applied to a rat sciatic nerve defect model in vivo to examine its effect on axonal regeneration and myelinization of the injured nerve.

    RESULTS AND CONCLUSION: The purity of olfactory ensheathing cells was (94.4±3.1)%. Compared with the blank control and low dose olfactory ensheathing cell culture groups, the average length of five longest axons in dorsal root ganglion tissue mass in the high dose olfactory ensheathing cells culture group was significantly increased (P < 0.05). Immunofluorescence showed that the regenerated nerve penetrated through the defect area and the regenerated nerve was arranged orderly in the olfactory ensheathing cell culture and the autologous nerve groups, which was significantly superior to that in the blank control group. Transmission electron microscope observed that the number of regenerated nerve axons and the thickness of myelin sheath in the olfactory ensheathing cell culture group were significantly higher than those in the blank control group (P < 0.05). These results indicate that the supernatant of the olfactory ensheathing cells can promote axonal regeneration after peripheral nerve injury and the myelination of the regenerated axons, which provides a new olfactory ensheathing cells-based acellular therapy for peripheral nerve injury.

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    Improving neuronal transfection by electroporation of dorsal root ganglion
    Qi Shibin, Ma Yanxia, Zhang Haonan, Ma Jinjin, Xu Jinhui, Saijilafu
    2020, 24 (19):  3042-3047.  doi: 10.3969/j.issn.2095-4344.2072
    Abstract ( 458 )   PDF (804KB) ( 257 )   Save

    BACKGROUND: Electroporation of dorsal root ganglion is a high-efficiency gene transfection method to study nerve regeneration. In the past, the voltage condition of dorsal root ganglion electroporation resulted in a reduction in the number of labeled neurons and axons, with a high statistical error.

    OBJECTIVE: To improve the marker rate of neurons and their axons, and to provide theoretical basis for the study of peripheral nerve regeneration.

    METHODS: The enhanced green fluorescent protein was as an outcome measure to optimize dorsal root ganglion electroporation in axonal regeneration. ICR mice were randomly divided into two groups, respectively, and underwent dorsal root ganglion electroperforation surgery to detect the labeling rates of neurons and their axons under the intervention of 35 and 60 V voltages.

    RESULTS AND CONCLUSION: Voltages at 35 and 60 V did not cause significant neuronal death. Compared with 35 V voltage, 60 V voltage significantly increased the labeling rate of neurons and their axons as well as the number of axons passing through the injured site (P < 0.05). The 60 V voltage did not damage the behavioral function of the experimental animals. These results suggest that 60 V voltage can increase the labeling rate of neurons and their axons, providing a basis for the study of axonal regeneration in peripheral nerves.

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    The role and application of mesenchymal stem cells-derived exosomes in the treatment of nervous system diseases
    Gao Zhencheng, Liu Xin
    2020, 24 (19):  3048-3054.  doi: 10.3969/j.issn.2095-4344.2040
    Abstract ( 422 )   PDF (774KB) ( 146 )   Save

    BACKGROUND: Due to the existence of the blood-brain barrier, macromolecular drugs cannot enter the brain tissue through the blood-brain barrier to exhibit their therapeutic effects. Therefore, many nervous system diseases and neurodegenerative diseases cannot be effectively treated. In recent years, studies have found that mesenchymal stem cells-derived exosomes are characterized by small volume and can be loaded with lipid, protein, nucleic acid and other signal substances, which can repair the tissue damage induced by ischemic or hemorrhagic stroke, Alzheimer's disease, epilepsy and spinal cord injury. Mesenchymal stem cell exosomes have gradually become an important tool for the treatment of neurological diseases.

    OBJECTIVE: To analyze and summarize the effects of mesenchymal stem cells-derived exosomes on the treatment of nervous system diseases from both macroscopic and microscopic perspectives, and to present the problems and precautions in the basic research and clinical trials of exosomes.

    METHODS: “Exosomes, extracellular vesicles, MSCs, mesenchymal stem cells, neurodegenerative diseases” were used as the English search terms. The PubMed database was searched by computer, and the articles describing the characteristics and repairing effects of mesenchymal stem cells-derived exosomes were included. Irrelevant articles were excluded. Finally, 35 articles were included for further analysis.

    RESULTS AND CONCLUSION: Mesenchymal stem cells-derived exosomes have biological characteristics such as crossing the blood-brain barrier easily, carrying abundant signal substances, and playing important roles in animal disease models, such as anti-inflammation, promotion of neuronal growth, maintaining the number of neurons, and promotion of neurite remodeling. Meanwhile, modified exosomes can play a more effective tissue-repairing function than natural exosomes, which can be used as a specific molecular drug carrier for the treatment of specific neurological diseases.

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    Mesenchymal stem cell-derived exosomes and regenerative medicine: outlook for future cell-free therapy in clinical practice
    Luo Yaxin, Bi Haoran, Chen Xiaoxu, Yang Kun
    2020, 24 (19):  3055-3062.  doi: 10.3969/j.issn.2095-4344.2071
    Abstract ( 542 )   PDF (839KB) ( 113 )   Save

    BACKGROUND: Exosomes are tiny membrane vesicle structures that are an important paracrine component of mesenchymal stem cells. They can transmit information to damaged cells or tissues for regeneration.

    OBJECTIVE: To review the exosomes and their research process in regenerative medicine.

    METHODS: Databases of PubMed and CNKI were retrieved with the keywords of “exosomes, mesenchymal stem cells, tissue regeneration and repair” in English and Chinese, respectively. After initial screening of titles and abstracts, irrelevant articles were excluded, and 63 eligible articles were included for result analysis.

    RESULTS AND CONCLUSION: Exosomes contain a variety of components, and their extraction methods are diverse. They have various functions, such as removing waste material, mediating information transfer between cells, generating immune tolerance and serving as a tumor treatment vaccine. Mesenchymal stem cell-derived exosomes play an important role in tissue regeneration and repair, and have good application prospects. However, if they are used as cell-free therapy in clinical practice, more in-depth research and exploration are needed.

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    Applications, roles and problems of exosomes derived from different stem cells in the treatment of cardiovascular diseases
    Liu Zu, Han Shen, Li Yaxiong, Li Kunlin, Zhang Yayong, Jiang Lihong
    2020, 24 (19):  3063-3070.  doi: 10.3969/j.issn.2095-4344.2023
    Abstract ( 493 )   PDF (770KB) ( 130 )   Save

    BACKGROUND: Exosomes contain DNA fragments, mRNA, miRNA, functional proteins, transcription factors and other substances with biological activities. Their membrane structure also expresses a variety of antigens and antibody molecules, thus producing various biological effects. Recent studies have shown that it has similar therapeutic effects with stem cell transplantation and can be used as a substitute of stem cell transplantation in the treatment of cardiovascular diseases.

    OBJECTIVE: To summarize the application of exosomes from different stem cells in the treatment of cardiovascular diseases, so as to provide reference and basis for exosomes applied in the treatment of cardiovascular diseases.

    METHODS: Articles in PubMed database from 2005 to 2019 were searched using the search terms of “exosomes, cardiovascular diseases, embryonic stem cells, induced pluripotent stem cells, mesenchymal stem cells.” Articles in databases of CNKI and VIP from 2014 to 2019 were retrieved with the search terms of “exosome, cardiovascular disease, embryonic stem cells, induced pluripotent stem cells, mesenchymal stem cells.” The literature and references were reviewed one by one.

    RESULTS AND CONCLUSION: Exosomes derived from stem cells are safer and more effective than stem cell transplantation, and have great potential in the prevention and treatment of cardiovascular diseases. However, the research on the function and use of exosomes is still in its infancy. In addition, low exosome content and cumbersome extraction process limit its clinical application.

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    Advances in stem cells research concerning tissue-engineered meniscus
    Qing Wanyi, Wang Xingxing, Zhou Shengliang, Fu Weili
    2020, 24 (19):  3071-3077.  doi: 10.3969/j.issn.2095-4344.2068
    Abstract ( 462 )   PDF (713KB) ( 69 )   Save

    BACKGROUND: Meniscus cartilage injury is a most common injury of knee joint. In the past decade, stem cell based therapies have been widely applied, and the related studies have been increased rapidly. Pluripotent stem cells have been shown to exist in the meniscus, which may play a key role in the healing of meniscus.

    OBJECTIVE: To determine the source and culture conditions of stem cells related to tissue-engineered meniscus, and to understand the current development status of tissue- engineered meniscus.

    METHODS: PubMed, Embase, EBSCO, Cochrane library, and Clinical library databases were retrieved for relevant articles published between 2009 and 2019. The articles concerning tissue-engineered meniscus and selection of seed cells were selected, and finally 64 eligible articles were included for analysis.

    RESULTS AND CONCLUSION: Stem cells have been extensively used as seed cells in tissue-engineered meniscus due to its high proliferation ability and multipotent property. These cells can effectively repair the meniscus in animals, but the clinical outcomes still remain unclear. Therefore, there is a certain distance from basic research to clinical application.

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    Potentials of pericytes in orthopedics
    Yu Mingchuan, Zhao Jinbing, Yin Ming, Yin Changchang
    2020, 24 (19):  3078-3083.  doi: 10.3969/j.issn.2095-4344.2036
    Abstract ( 439 )   PDF (643KB) ( 78 )   Save

    BACKGROUND: Pericytes and other perivascular stem cells are gaining increasing attention in bone tissue engineering. Pericytes have been long thought to regulate blood pressure and promote angiogenesis. However, it is now considered to have the characteristics of mesenchymal stem cells, including pluripotency, self-renewal, immune regulation, and tissue repair, showing strong regenerative potential in common orthopedic diseases such as fractures, nonunion, vertebral fusion, ligament rupture, and cartilage injury.

    OBJECTIVE: To summarize the related applications of pericytes in orthopedics, and to explore mechanisms, strengths and limitations.

    METHODS: With “pericytes, perivascular stem cells, repair, therapy, orthopedics” as Chinese and English retrieval terms, we systematically searched databases including PubMed, Web of Science, CNKI and WanFang, from inception to August 2019 for the articles concerning the treatment of orthopedic diseases with pericytes. A total of 112 related documents were retrieved. After reading the full text, 55 eligible documents were selected.

    RESULTS AND CONCLUSION: Pericytes are a kind of emerging stem cells that have been reported in many studies regarding the treatment of orthopedic diseases, and have a greatly therapeutic prospect. There are abundant pericytes in the body with no need for in vitro culture. The repair mechanism of pericytes is mainly related to paracrine mediation, with self-differentiation as a secondary mechanism. However, its specific mechanism remains unclear, which needs further investigations.

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    Application and research advances in stem cell transplantation for severe aplastic anemia
    Ding Yubin, Tang Yufeng, Tang Xudong
    2020, 24 (19):  3084-3092.  doi: 10.3969/j.issn.2095-4344.2037
    Abstract ( 450 )   PDF (745KB) ( 152 )   Save

    BACKGROUND: Allogeneic hematopoietic stem cell transplantation is still the only cure method for acquired severe aplastic anemia. How to select patients for treatment has become a research hotspot in recent years.

    OBJECTIVE: To review the progress of allogeneic hematopoietic stem cell transplantation from three aspects: HLA full-phase matched unrelated donor hematopoietic stem cell transplantation (MUD-HSCT), unrelated cord blood transplantation (UCBT) and haploidentical hematopoietic stem cell transplantation (HID-HSCT).

    METHODS: Literatures on allogeneic hematopoietic stem cell transplantation for severe aplastic anemia collected in PubMed, CNKI full-text database and WanFang database from 2000 to 2018 were retrieved with the keywords “unrelated donor; haploidentical; unrelated cord blood; severe aplastic anemia” in Chinese and English.

    RESULTS AND CONCLUSION: MSD-HSCT is the first-line treatment for severe aplastic anemia, but in view of China’s special national conditions, HLA matched donor is not easy to find. As an important alternative treatment, MUD-HSCT is close to MSD-HSCT. However, the incidence of graft versus host disease and severe infection after MUD-HSCT is still higher than that after MSD-HSCT. It is still necessary to consider multiple factors when choosing MUD-HSCT treatment. Umbilical cord blood hematopoietic stem cells are widely used because of their abundant sources and high match success rate. The probability of UCBT is very high when the amount of pre-frozen total nucleated cells is more than 3.9×107/kg. However, in view of the delay of UCBT and immune function reconstruction, unless other transplantation methods are not feasible in clinical treatment of severe aplastic anemia and immunosuppressive therapy fails in the first course of treatment, UCBT should not be considered. HID-HSCT has the advantages of easy access and good compliance of donors and is close to full-matched transplantation. It has become an important alternative to transplantation. The use of baliximab and/or antithymocyte globulin is expected to reduce the incidence of graft versus host disease and expand the clinical application of HID-HSCT.

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    Current status of hematopoietic stem cell transplantation in the treatment of aplastic anemia
    Wei Yuanfeng, Huang Dongping
    2020, 24 (19):  3093-3100.  doi: 10.3969/j.issn.2095-4344.2073
    Abstract ( 620 )   PDF (826KB) ( 87 )   Save

    BACKGROUND: A great progress has been achieved in the allogeneic hematopoietic stem cell transplantation for aplastic anemia. However, graft-versus-host disease and graft failure after transplantation are still the main causes of non-relapse death, which seriously affect the survival of patients.

    OBJECTIVE: To summarize the current status and progress of allogeneic hematopoietic cell transplantation in the treatment of aplastic anemia.

    METHODS: The first author retrieved PubMed, CNKI, WanFang and VIP databases for the articles concerning allogeneic hematopoietic stem cell transplantation for aplastic anemia published from January 1990 to September 2019. The keywords were “aplastic anemia, matched sibling donor hematopoietic stem cell transplantation, unrelated donor hematopoietic stem cell transplantation, haploidentical hematopoietic stem cell transplantation, cord blood transplantation” in Chinese and English, respectively. Finally 55 eligible articles were included for result analysis.

    RESULTS AND CONCLUSION: HLA-matched sibling donor allogeneic hematopoietic stem cell transplantation is the first choice. Unrelated donor hematopoietic stem cell transplantation may be an effective and feasible first-line therapy in pediatric severe aplastic anemia patients with no matched sibling donors. Haploidentical hematopoietic stem cell transplantation and cord blood transplantation can also be important transplantation methods for severe aplastic anemia when lack of HLA-matched donors.

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    Immunoregulation of dental tissue-derived mesenchymal stem cells and its significance in oral diseases and tissue regeneration
    Chen Qianqian, Shen Mengjie, Yang Kun, Liu Qi
    2020, 24 (19):  3101-3107.  doi: 10.3969/j.issn.2095-4344.2080
    Abstract ( 400 )   PDF (733KB) ( 140 )   Save

    BACKGROUND: Dental tissue-derived mesenchymal stem cells can be isolated from different tissues such as dental pulp, periodontal ligament, exfoliated deciduous teeth, apical papilla, dental follicle, gingiva and other tissues. A large number of experimental studies have found that the effect of dental tissue-derived mesenchymal stem cells on immune cells may depend on many factors such as the surrounding microenvironment, the tissue source of the stem cells and the type of immune cell preparation. Moreover, it has been proved that activated immune cells can up-regulate the immunomodulatory activity of dental tissue-derived mesenchymal stem cells, and this research on the immunomodulatory activity of dental tissue-derived mesenchymal stem cells will lay the foundation for its application in regenerative repair.

    OBJECTIVE: To review the research progress of dental tissue-derived mesenchymal stem cells in immune regulation.

    METHODS: A computer-based search of China Biology Medicine (CBM), CNKI, PubMed and Elsevier databases was performed, and the search terms included “immunomodulation; immune system; mesenchymal stem cells; regeneration; oral diseases; pathogenic bacteria; dental-tissue.” We reviewed related articles regarding the immunoregulation of dental tissue-derived mesenchymal stem cells published from 2000 to 2019, including reviews, basic research, and clinical research. Preliminary screening of reading titles and abstracts was performed to exclude documents that are not related to the topic of the article. Based on the inclusion and exclusion criteria, 88 articles were finally included for result analysis.

    RESULTS AND CONCLUSION: In recent years, dental tissue-derived mesenchymal stem cells have been widely used, but the immunomodulatory effect of dental tissue-derived mesenchymal stem cells is not clear. The interaction between dental tissue-derived mesenchymal stem cells and immune cells represents a mechanism that contributes to the study of tissue homeostasis and inflammatory diseases. Therefore, immunomodulation-based strategies may be a very promising tool. This paper reviews the complex mechanism of the interaction between dental tissue-derived mesenchymal stem cells and immune cells and discusses the potential significance of its mediated immunoregulation in the progression of oral diseases and oral tissue regeneration.

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    Cell labeling and tracking imaging in vivo: newest advance in animals and humans
    Xu Mengxin, Li Yijia, Liu Zhibo
    2020, 24 (19):  3108-3116.  doi: 10.3969/j.issn.2095-4344.2077
    Abstract ( 634 )   PDF (925KB) ( 360 )   Save

    BACKGROUND: Various cell therapy products have been approved by clinical trials worldwide, and cell therapies such as stem cell therapy and adoptive immunotherapy have attracted much attention. Real-time observation and imaging in vivo can visualize the distribution of cells, track cell movement, monitor cell viability, and observe the cell migration and growth. Many imaging technologies can visualize cells in vivo, such as ultrasound, optics, MRI and nuclear imaging, and these methods need to correspond to different labeling and detection strategies. Each strategy has its own advantages and disadvantages.

    OBJECTIVE: To review the principle and development of different tracking methods, and their application in animals and humans.

    METHODS: PubMed, Google Scholar, Web of Science and CNKI databases were searched with the keywords of “cell tracking, in vivo cell tracking, PET imaging, MRI, optical imaging.” The articles published in the past 5-10 years were preferred. The contents of the articles mainly describe the principle of different tracking methods, and their application in animal models and patients.

    RESULTS AND CONCLUSION: In the past 20 years, cell tracking has developed into a multifarious discipline, not only establishing a variety of robust methods in animal models, but also proving the feasibility of clinical transformation in some human studies. The development of the non-invasive detection methods, such as PET and MRI, and new contrast agents provides strong support for the application of cell therapy in clinical and scientific researches.

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