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    08 July 2022, Volume 26 Issue 19 Previous Issue   
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    Echinococcus granulosus promotes the proliferation of bone marrow mesenchymal stem cells
    Liang Xueqi, Zhou Hui, Wu Jie, Xi Yu, He Jiageng, Qin Le, Chen Xueling, Wu Xiangwei, Sun Fan, Niu Jianhua
    2022, 26 (19):  3004-3010.  doi: 10.12307/2022.378
    Abstract ( 549 )   PDF (2239KB) ( 64 )   Save
    BACKGROUND: At present, there are few reports on the interaction between Echinococcus granulosus and mesenchymal stem cells at home and abroad, and the research on Echinococcus granulosus and stem cell proliferation is still blank.  
    OBJECTIVE: To explore the effect and mechanism of Echinococcus granulosus on the proliferation of bone marrow mesenchymal stem cells.
    METHODS:  C57BL/6 mouse bone marrow mesenchymal stem cells were isolated and cultured, and divided into bone marrow mesenchymal stem cell group, Notch signaling pathway specific inhibitor DAPT group, Echinococcus granulosus protocercaria group, and Echinococcus granulosus protocercaria + specific inhibitor DAPT group. At 1, 2, and 3 days after culture, CCK-8 assay was used to detect the proliferation of bone marrow mesenchymal stem cells in each group. Western blot assay and real-time fluorescent quantitative PCR were used to detect expression levels of Notch-1, Jagged-1, Hes-1 proteins and mRNA related to the Notch signaling pathway in bone marrow mesenchymal stem cells of each group.  
    RESULTS AND CONCLUSION: (1) Compared with bone marrow mesenchymal stem cell group, and the proliferation was inhibited in the specific inhibitor DAPT group (P < 0.05), and the proliferation of the Echinococcus granulosus protocercaria group was significant (P < 0.05). Compared with the specific inhibitor DAPT group, the proliferation significantly increased in the Echinococcus granulosus protocercaria + specific inhibitor DAPT group (P < 0.05). (2) The protein and mRNA expression levels of Notch-1, Jagged-1, and Hes-1 were lower in the specific inhibitor DAPT group than those in the bone marrow mesenchymal stem cell group (P < 0.05). These expression levels in the Echinococcus granulosus protocercaria group were higher than those in the bone marrow mesenchymal stem cell group (P < 0.05); these expression levels were higher in the Echinococcus granulosus protocercaria + specific inhibitor DAPT group than those of the specific inhibitor DAPT group (P < 0.05). (3) In conclusion, Echinococcus granulosus can promote the proliferation of bone marrow mesenchymal stem cells through Notch signaling pathway. This phenomenon may lay a theoretical foundation for the formation mechanism of the outer cyst of Echinococcus granulosus, thus explaining how to obtain immune escape after the host is infected with Echinococcus granulosus. It may even open a new research direction for the prevention and early diagnosis of Echinococcus granulosus.
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    Effect of ATR gene knockdown on senescence and function of rat bone marrow endothelial progenitor cells
    Tang Mi, Qin Zhen, Wei Zhengxin, Ni Ming, Chai Xiaokang
    2022, 26 (19):  2985-2990.  doi: 10.12307/2022.375
    Abstract ( 408 )   PDF (2932KB) ( 116 )   Save
    BACKGROUND: Endothelial progenitor cells play an important role in vascular endothelial renewal and repair. The transplantation of autologous endothelial progenitor cells expanded and cultured in vitro to promote angiogenesis in ischemic sites has become a new strategy for the prevention and treatment of ischemic cardiovascular diseases. However, the endothelial progenitor cells derived from the elderly body will show signs of cellular senescence when expanded in vitro. The ability of aging endothelial progenitor cells to repair vascular endothelium is difficult to exert. Studies have shown that DNA damage is closely related to cell aging, and DNA damage detection points are an important checkpoint for regulating DNA damage.  
    OBJECTIVE: Lentiviral RNA interference technology was used to knockdown ATM and Rad3-related kinase (ATR) gene in rat bone marrow endothelial progenitor cells, and to explore its role in the aging process of endothelial progenitor cells.
    METHODS: Endothelial progenitor cells from bone marrow in rats were isolated, cultured and identified. After the isolated endothelial progenitor cells were cultured to the third generation, they were counted and randomly divided into three groups: non-infection control group (blank group), negative control group, and gene knockdown group (ATR-RNAi group). The non-infection control group was cultured normally, and the negative control group and gene knockdown group were stably transfected with lentiviral RNAi and lentiviral ATR-RNAi to day 3 and day 6, respectively. The level of ATR mRNA in each group of cells was detected by qRT-PCR. The protein expression of ATR in each group of cells was detected by western blotting. The senescence of each group of cells was detected by β-galactosidase staining. MTT colorimetric method was used to detect cell proliferation activity in each group. Transwell chamber and in vitro angiogenesis kit were used to detect cell migration ability and tubule formation of each group. Flow cytometry was applied to detect the cell cycle change in each group.
    RESULTS AND CONCLUSION:  (1) Compared with the non-infection control group, the expression levels of ATR mRNA and ATR protein in the endothelial progenitor cells in ATR-RNAi group were decreased significantly (P < 0.01), indicating that ATR gene expression was effectively reduced. (2) Compared with the non-infection control group, the number of blue-stained cells in the ATR-RNAi group decreased, indicating that the degree of aging was significantly reduced (P < 0.01). (3) Compared with the non-infection control group, cell proliferation, migration and tubule formation in the ATR-RNAi group were significantly enhanced (P < 0.05). (4) Compared with the non-infection control group, the percentages of cells in the G1 and G2 phases in the ATR-RNAi group were decreased significantly, and the percentage of cells in the S phase was increased significantly (P < 0.05). (5) These results indicate that knockdown of the expression of ATR genes could delay the aging process of endothelial progenitor cells, promotes the function of endothelial progenitor cells, and reduces the stagnation of cell cycles.
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    Effect of RAB39B gene based on CRISPR/Cas9 technology on cartilage differentiation of bone marrow mesenchymal stem cells
    Ma Dujun, Peng Liping, Zhou Ziqiong, Zhao Jing, Zhu Houjun, Jiang Shunwan, Zhong Jing, She Ruihao
    2022, 26 (19):  2978-2984.  doi: 10.12307/2022.374
    Abstract ( 486 )   PDF (2860KB) ( 79 )   Save
    BACKGROUND: Based on previous research, the research team used proteomics and high-throughput sequencing to screen the correlation between the RAB39B gene and the proliferation and cartilage differentiation of bone marrow mesenchymal stem cells.  
    OBJECTIVE: To investigate the effect of RAB39B gene knockout by CRISPR/Cas9 gene editing technology on cartilage differentiation of bone marrow mesenchymal stem cells.
    METHODS:  CRISPR/Cas9 lentivirus infection method was used to construct stable transfection cell line of RAB39B gene knockdown. Rabbit bone marrow mesenchymal stem cells were divided into normal control group, no-load control group, and RAB39B knockout group. The knockout effect of CRISPR/Cas9 system on RAB39B was evaluated by western blot assay. The proliferation activity of bone marrow mesenchymal stem cells was detected by CCK-8 assay. The apoptosis rate of bone marrow mesenchymal stem cells was detected by flow cytometry. The mRNA expression of COLII and COLX was detected by qRT-PCR. The expression levels of RHOA, LIMK, and Sox9 proteins in chondrogenic differentiation related pathways of bone marrow mesenchymal stem cells were detected by western blot assay.  
    RESULTS AND CONCLUSION: (1) Lentivirus carrying knockout RAB39B gene plasmid was found to be highly expressed in rabbit bone marrow mesenchymal stem cells 48-96 hours after infection. Western blot assay showed that the expression of RAB39B protein in bone marrow mesenchymal stem cells was significantly decreased after RAB39B knockout (P < 0.01). (2) Compared with the normal control group and the empty control group, the cell proliferation activity of the RAB39B gene knockout group was significantly reduced (P < 0.01); the apoptosis rate was increased (P < 0.01); the expression of COLII and COLX mRNA was significantly reduced (P < 0.01); RHOA, LIMK, and Sox9 protein expression was significantly decreased (P < 0.01). (3) These findings indicate that RAB39B gene knockout by CRISPR/Cas9 system can inhibit the proliferation of bone marrow mesenchymal stem cells, promote cell apoptosis, and reduce the chondrocyte differentiation ability, which indicates that RAB39B gene may affect the proliferation and chondrocyte differentiation ability of bone marrow mesenchymal stem cells, and its specific mechanism needs further study.
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    Icariin alleviates osteoporosis by promoting osteogenic differentiation of bone marrow mesenchymal stem cells in mice
    Zhang Jinming, Tian Yingzhou, Zhao Ling, Xiong Lihua, Wang Qiuping, Song Wei, Wen Jianxuan
    2022, 26 (19):  2991-2996.  doi: 10.12307/2022.376
    Abstract ( 506 )   PDF (1646KB) ( 40 )   Save
    BACKGROUND: Icariin is the main active ingredient of epimedium, a commonly used Chinese herbal medicine for the treatment of osteoporosis, but its molecular mechanism needs to be studied in depth.
    OBJECTIVE: To explore the effect and mechanism of icariin on osteoporosis in mice.
    METHODS: The osteoporosis models of C57BL/6 mice were constructed by subcutaneous injection of dexamethasone for 5 weeks. Totally 20 successfully modeled mice were randomly divided into a model group and a treatment group (n=10). An additional 10 non-modeled C57BL/6 mice were used as a control group. The treatment group was given a suspension of icariin and saline by intragastric administration; the model group and the control group were given the same amount of saline, once a day. The state of the mice was monitored every day during the administration, and the body weight was measured. Two months after the treatment, Micro-CT machine was used to scan the proximal tibia metaphysis to analyze the microstructure of the bone tissue in mice, and to study the therapeutic effect of icariin on osteoporosis in mice. Simultaneously, bone marrow mesenchymal stem cells were isolated and cultured in each group. The expression levels of alkaline phosphatase, osteogenic specific transcription factor, osteocalcin, transforming growth factor β, and RUNX family transcription factor 2 were detected by flow cytometry. The expression levels of osteopontin, bone sialoprotein, and peroxisome proliferator activated receptor γ mRNA were determined using qRT-PCR. Alizarin red staining and oil red O staining were applied to detect osteogenic and adipogenic differentiation.  
    RESULTS AND CONCLUSION: (1) Compared with the control group, the bone wet weight, bone volume fraction, trabecular thickness, and trabecular number significantly decreased (P < 0.01), trabecular separation became larger (P < 0.001), and bone cortical thickness became thinner in the model group (P < 0.001). Compared with the model group, above indicators of mice in the treatment group were significantly improved (P < 0.05). (2) Compared with the model group, the expression of osteogenic related genes or proteins was significantly increased (P < 0.05), and the expression level of lipogenic related gene peroxisome proliferator activated receptor gamma mRNA was significantly decreased in the treatment group. (3) Compared with the model group, the absorbance value of alizarin red staining was significantly increased in mouse bone marrow mesenchymal stem cells of the treatment group (P < 0.05), while the absorbance value of oil red O staining was significantly reduced (P < 0.05). (4) The results suggest that icariin may relieve osteoporosis by promoting osteogenic differentiation of mouse bone marrow mesenchymal stem cells, inhibiting their adipogenic differentiation, improving bone marrow microenvironment, and finally promoting trabecular bone formation.
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    5-Azacytidine combined with bone morphogenetic protein 2 induces differentiation of bone marrow mesenchymal stem cells into cardiomyocyte-like cells
    Wang Wenhua, Liu Yang, Wang Qiaomin, Lü Yang, Zhao Yaru, Wang Haiping
    2022, 26 (19):  2958-2963.  doi: 10.12307/2022.371
    Abstract ( 341 )   PDF (1699KB) ( 33 )   Save
    BACKGROUND: Stem cells have become ideal seed cells in tissue engineering, which provides a research direction for cell transplantation in the treatment of myocardial infarction.
    OBJECTIVE: To investigate the feasibility of bone morphogenetic protein 2 combined with 5-azacytidine on the differentiation of bone marrow mesenchymal stem cells into cardiomyocyte-like cells in vitro.
    METHODS: Bone marrow mesenchymal stem cells were cultured by whole bone marrow culture adherent method. The third generation of bone marrow mesenchymal stem cells was divided into four groups: control group (ordinary Iscove’s modified Dulbecco’s medium), bone morphogenetic protein 2 group (200 ng/L), 5-azacytidine group (10 µmol/L), 5-azacytidine and bone morphogenetic protein 2 group. After induction for 3 days, the normal medium was changed and cultured for 4 weeks. The expression of cTnI was detected by immunocytochemistry. The expression of Desmin and cTnT was detected by immunofluorescence. The expression of cTnT and cTnI was detected by western blot assay. After 3 days of induction, the normal medium was changed and cultured for 1, 2 and 4 weeks. The mRNA expression of GATA-4 and Nkx2.5 was detected by RT-qPCR.  
    RESULTS AND CONCLUSION: (1) Western blot assay showed that cTnT and cTnI were expressed in the induction group. The expression levels of cTnT and cTnI in the combined group were higher than those in other groups (P < 0.01). (2) Immunocytochemistry showed positive expression of cardiac troponin (cTnI) in the induction group; the expression was higher in the combined group than that in the induction group (P < 0.05). Immunofluorescence cytochemistry assay showed the positive expression of Desmin and cTnT; the expression in the combined group was higher than that in the induction group (P < 0.05). (3) RT-qPCR showed the mRNA expression of GATA-4 and Nkx2.5 in the induction group; the expression was higher in the combined group than that in the induction group (P < 0.05). (4) The results showed that bone marrow mesenchymal stem cells induced by 5-azacytidine and bone morphogenetic protein 2 could improve the differentiation efficiency of cardiomyocyte-like cells. 
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    Mechanism by which bone marrow mesenchymal stem cells improve cognitive function in APP/PS1 double transgenic mice
    Gu Qingfang, Guo Minfang, Liu Xiaoqin, Mu Bingtao, Li Weimei, Song Lijuan, Chai Zhi, Ma Cungen, Yu Jiezhong
    2022, 26 (19):  2964-2969.  doi: 10.12307/2022.372
    Abstract ( 597 )   PDF (1473KB) ( 44 )   Save
    BACKGROUND: Studies have shown that bone marrow mesenchymal stem cell therapy can effectively fill the neurons lost in Alzheimer’s disease patients, but the specific mechanism of action needs to be further clarified.  
    OBJECTIVE: To explore the therapeutic effects of bone marrow mesenchymal stem cells in APP/PS1 double transgenic mice with Alzheimer’s disease and its mechanism.
    METHODS:  APP/PS1 double transgenic mice were selected as the research objects and were randomly divided into model and bone marrow mesenchymal stem cell groups (n=10 per group). Ten wild-type C57BL/6 mice of the same month and the same sex were selected as the normal control group. The mice were treated with bone marrow mesenchymal stem cells (1×106/time) or normal saline, and repeated administration once a week, for 2 months via nasal cavity. Morris water maze test was applied to examine cognitive function of mice. Western blot assay was used to detect the expression of related factors of pathological markers, inflammatory molecules and oxidative stress proteins in the brain tissues of mice.  
    RESULTS AND CONCLUSION: Bone marrow mesenchymal stem cells effectively improved the cognitive dysfunction of Alzheimer’s disease mice, increased the expression of APP protein and decreased expression of phosphorylated tau protein, reduced the expression of Toll like receptor 2, inducible nitric oxide synthase, nuclear transcription factor kappa B and increased the expression of nuclear factor erythroid 2-related factor 2 and heme oxygenase-1. It is concluded that bone marrow mesenchymal stem cells have a potential role in the treatment of Alzheimer’s disease; the mechanism exerts the effects of the anti-inflammation and antioxidation through nuclear factor erythroid 2-related factor 2/heme oxygenase-1 signaling pathway.
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    Effect of bone marrow mesenchymal stem cell conditioned medium on the proliferation of multiple myeloma cells
    Huang Mei, Wang Feiqing, Liang Huiling, Yang Xu, Zhao Jianing, Wang Kun, Liu Yanqing, Zhou Yuan, Wang Jishi, Li Yanju, Liu Yang
    2022, 26 (19):  3024-3029.  doi: 10.12307/2022.381
    Abstract ( 504 )   PDF (2226KB) ( 49 )   Save
    BACKGROUND: In recent years, relationship between the bone marrow microenvironment and the growth, survival and drug resistance of multiple myeloma cells has become a research hotspot for researchers. Few studies have evaluated the effects of bone marrow mesenchymal stem cells conditioned culture medium on multiple myeloma cell lines.  
    OBJECTIVE: To investigate the effect of bone marrow mesenchymal stem cell conditioned medium on the proliferation of multiple myeloma cell lines.
    METHODS:  Ficoll density gradient centrifugation and adherent method were used to purify bone marrow mesenchymal stem cells from healthy donors. The supernatants of 3-5 generations of bone marrow mesenchymal stem cells were collected in the culture medium. Ultrafiltration centrifuge tube was used to prepare bone marrow mesenchymal stem cell conditioned medium and to prepare 1640 complete medium containing 10% human bone marrow mesenchymal stem cell conditioned medium so as to induce the culture of multiple myeloma cell lines RPMI8226 and U266 for 48 hours. Cell proliferation was detected by MTT assay and EdU fluorescence staining. Cell apoptosis was detected by flow cytometry and PI fluorescence staining. Real-time PCR and western-blot assay were used to detect mRNA and protein levels of multiple myeloma cell lines BCL-2 and BTK.  
    RESULTS AND CONCLUSION: Bone marrow mesenchymal stem cell conditioned medium could promote the proliferation of multiple myeloma cell lines (P < 0.05), reduce the apoptosis rate of cancer cells (P < 0.05) and was associated with high mRNA and protein expression of BCL-2 and BTK (P < 0.05). The results showed that the bone marrow mesenchymal stem cell conditioned medium promoted the proliferation multiple myeloma cell lines.
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    Expansion and identification of primary rat adipose-derived mesenchymal stem cells in vitro
    Liu Haiqin, Ma Huagen, Tang Yuanyu
    2022, 26 (19):  2953-2957.  doi: 10.12307/2022.370
    Abstract ( 502 )   PDF (5021KB) ( 40 )   Save
    BACKGROUND: Adipose-derived mesenchymal stem cells can regulate endocrine metabolism, maintain the homeostasis of microenvironment around adipocytes, participate in the development of adipocytes, and play an important regulatory role in lipid metabolism and the occurrence and development of obesity. At present, type I collagenase digestion is mainly used for the culture of adipose-derived mesenchymal stem cells in vitro, but it has the disadvantages of long digestion time and low efficiency. How to select appropriate digestive enzymes to shorten digestion time and improve experimental efficiency is worthy of attention and exploration.  
    OBJECTIVE: To establish a method for primary culture of rat adipose-derived mesenchymal stem cells in vitro, and to provide important cell carriers for clinical development of stem cell therapy and gene therapy. 
    METHODS: Under aseptic condition, the adipose tissue from the bilateral groin and epididymis of rats was taken out, cut into paste with iris scissors. Totally 2 mL of 0.1% type II collagenase was added for digestion for 45 minutes. After washing and centrifugation, the adipocytes were inoculated in low-sugar DMEM complete medium containing 10% fetal bovine serum and placed in the CO2 incubator for primary culture. When the fusion rate reached 80%-90%, the cells were subcultured at the ratio of 1:3. The morphological changes of cells were observed under the inverted microscope. The fourth generation of adipose-derived mesenchymal stem cells was detected for specific cell surface marker CD molecules, and the adipogenic and osteogenic differentiation experiments were carried out. 
    RESULTS AND CONCLUSION: (1) After 3 days of culture, a small number of short spindle cells crawled out. 5 days later, the cells grew like colonies or clusters, and the shape was long spindle. After 6-8 days, the colonies fused 80%-90% with each other, arranged in a vortex and then subcultured. In the third generation, the cells grew rapidly and could be subcultured again 48 hours after inoculation, and the cells had uniform morphology and showed obvious fish like growth. (2) Flow cytometry showed that CD90, CD73, and CD29 were positive, while CD34, CD45, and CD11b/c were negative. (3) At 7-10 days after adipogenic differentiation of the fourth generation of adipose-derived mesenchymal stem cells, cell morphology gradually changed from a long spindle to a polygonal or round shape, and fat droplets of various sizes accumulated in the cytoplasm. Oil red O staining exhibited that fat droplets were bright and deep red. At 21 days after osteogenic differentiation, the cells gradually changed from a long spindle shape to a polygonal shape, growing in an aggregated shape, with small black particles of varying sizes on the surface, and mineralized crystals were visible in some parts. Alizarin red staining displayed “mushroom-like” dark red spherical nodules scattered in different sizes. (4) It is concluded that this experiment successfully established a simple and efficient method for primary culture of rat adipose-derived mesenchymal stem cells.
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    Comparison of biological characteristics of two kinds of primary isolated human umbilical cord mesenchymal stem cells under three-dimensional culture
    Chen Siming, Hu Jiawei, Li Lili, Wu Yongqiang, Peng Weijie
    2022, 26 (19):  2997-3003.  doi: 10.12307/2022.377
    Abstract ( 691 )   PDF (3019KB) ( 100 )   Save
    BACKGROUND: The human umbilical cord mesenchymal stem cells isolation methods mainly include enzymatic digestion and tissue attachment. It is important to understand the biological characteristics of the two methods isolated cells in two-dimensional and three-dimensional culture conditions; it is of great significance to the selection of cell isolation methods and culture condition in tissue engineering.  
    OBJECTIVE: To compare the biological characteristics of human umbilical cord mesenchymal stem cells from the enzymatic digestion and tissue attachment methods in two-dimensional and three-dimensional culture conditions.
    METHODS:  Human umbilical cord mesenchymal stem cells were isolated by digestion method and tissue attachment method, amplified and cultured to passage 3 and divided into two-dimensional and three-dimensional culture. Scanning electron microscope was used to observe the cell spheroids. Live\dead staining was utilized to detect cell spheroid survival. Alamar Blue was applied to detect cell proliferation. Flow cytometry was used to detect the expression of immunophenotypes CD34, CD44, CD45, CD90, and CD105. Immunofluorescence and western blot assay were used to detect the expression of pluripotent transcription factors Sox2, Nanog, and Oct4.  
    RESULTS AND CONCLUSION: (1) Enzymatic digestion method took shorter time to obtain cells than the attachment method. The cell proliferation ability of the attachment method was better than that of the enzyme digestion under two-dimensional culture, but the proliferation was slow and there was no difference under three-dimensional culture conditions. After 3 days of spheroid culture, the cells became compact spheroids and survived well. (2) The cells isolated by the two methods all expressed CD44, CD90, and CD105 under two-dimensional and three-dimensional culture conditions, but did not express CD34 and CD45. Under two-dimensional culture, the expression of CD105 cells isolated by enzymatic digestion was higher than that of tissue attachment method; under three-dimensional culture, the expression of CD90 and CD105 cells isolated by enzymatic digestion was also higher than that of tissue attachment method. (3) Both isolation methods under two-dimensional and three-dimensional culture expressed pluripotency transcription factors Sox2, Nanog, and Oct4. Under the two-dimensional culture, the expression of the three transcription factors of the cells extracted by the enzymatic digestion method was higher than that of the tissue attachment method. However, under the three-dimensional culture, the expression of Sox2 in the tissue attachment method was higher than that of the enzymatic digestion method, and the expression levels of Nanog and Oct4 were not different between the two groups.
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    Extraction, identification and proteomic analysis of exosomes derived from human umbilical cord mesenchymal stem cells
    Shan Zhengming, Tao Shuchun, Hu Chunmei, Zhang Zhiyuan, Ding Yinan, He Mengcheng, Tang Qiusha
    2022, 26 (19):  3036-3042.  doi: 10.12307/2022.383
    Abstract ( 680 )   PDF (1739KB) ( 75 )   Save
    BACKGROUND: Current proteomics studies of exosomes only have proteomic comparisons between exosomes from different sources or exosomes secreted under different conditions. There is no comparative analysis between exosomes and their parent cells.  
    OBJECTIVE: To extract, identify and analyze the exosomes of human umbilical cord mesenchymal stem cells.
    METHODS:  Human umbilical cord mesenchymal stem cells were cultured and exosomes were extracted using sequential ultrafiltration and identified using transmission electron microscope, nanoparticle tracking analysis, bicinchoninic acid, western blot assay, and proteomics analysis.  
    RESULTS AND CONCLUSION: (1) The extracted exosomes had good dispersion and uniformity. Most of them were cup-shaped or round-like membranous vesicles. The double membranous structure of the vesicles could be seen, with low electron density components in the center, which were more concentrated and distributed. The boundary was clear. (2) The peak size distribution of exosomes was (129.5±8.7) nm. The membrane surface was negatively charged; the concentration was 8.375×1010 particles/mL; and the average zeta potential was (-28.1±3.6) mV. (3) Exosomes showed the expression of characteristic membrane proteins CD9 and CD63. (4) Proteomics analysis showed that most of the highly expressed proteins in exosomes were involved in biological processes, such as RNA splicing, mRNA processing, and protein folding, involved in the synthesis, processing, and degradation of RNA/DNA and other geneticmaterial and proteins, and participated in the composition of organelles and subcellular membrane structures, involved in multiple signal pathways, cell adhesion, extracellular matrix receptor interactions, and were also closely related to a variety of diseases and viral carcinogenesis. (5) It is concluded that after proteomics analysis, it is believed that the exosomes have certain homogeneity and differences compared with their parent cells. Differential protein function has nothing to do with immunity. Therefore, the low immunogenicity and safety of exosomes derived from human umbilical cord mesenchymal stem cells are verified.
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    Effects of different fimA genotypes of Porphyromonas gingivalis on the secretion related proteins and cytokines in human umbilical vein endothelial cells
    Li Kun, An Jie, Dong Suge, Cui Lili, Liu Lei, Li Tingting
    2022, 26 (19):  3043-3047.  doi: 10.12307/2022.384
    Abstract ( 347 )   PDF (1091KB) ( 28 )   Save
    BACKGROUND: Porphyromonas gingivalis infection is a risk factor that has been found to be related to atherosclerosis and other diseases in recent years. However, different fimA genotypes of Porphyromonas gingivalis have different pathogenic abilities. Actively explore Porphyromonas gingivalis high-risk bacterial strains play an important role in improving the diagnosis and treatment mechanism of atherosclerosis.  
    OBJECTIVE: To investigate the effects of different fimA genotypes of Porphyromonas gingivalis on the secretion of monocyte chemoattractant protein-1, interleukin-6, and endothelin-1/nitric oxide in human umbilical vein endothelial cells.
    METHODS:  Porphyromonas gingivalis genotypes IV, II, and I fimA were cultured under anaerobic conditions, and the multiplicity of infection was 100 to infect human umbilical vein endothelial cells. In the positive control group, Porphyromonas gingivalis lipopolysaccharide was used to stimulate human umbilical vein endothelial cells, and in the negative control group, human umbilical vein endothelial cells were cultured with cell culture medium only. Enzyme-linked immunosorbent assay was used to detect the levels of monocyte chemoattractant protein 1, interleukin 6, endothelin 1/nitric oxide in the culture supernatant of human umbilical vein endothelial cells after 2, 6, and 24 hours in each group.  
    RESULTS AND CONCLUSION: Except for the negative control group, the levels of interleukin 6, endothelin 1/nitric oxide, and monocyte chemoattractant protein 1 in the culture supernatant of human umbilical vein endothelial cells in the other four groups gradually increased. The levels of interleukin 6, endothelin 1/nitric oxide in the iv fimA genotype stimulation group were higher than those in the ii and i fimA genotype stimulation groups and the positive control group and the negative control group (P < 0.05). The level of monocyte chemoattractant protein 1 in the  ii fimA genotype stimulation group was higher than that in the iv,  i fimA genotype stimulation group and the negative control group (P < 0.05). The results indicate that there are certain differences in the dysfunction mechanisms of Porphyromonas gingivalis with different fimA genotypes in stimulating human umbilical vein endothelial cells. The  ii fimA genotype and  iv fimA gene have a strong ability to up-regulate the secretion of monocyte chemoattractant protein 1, interleukin 6, and endothelin 1/nitric oxide, and may play a dominant role in causing vascular vein endothelial cell dysfunction.
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    Effects of miR-7-5p on stem cell-like properties of human gastric cancer SGC-7901 cells
    Guo Junfu, Li Xiangnan, Ma Tianchi, Miao Lanying
    2022, 26 (19):  3030-3035.  doi: 10.12307/2022.382
    Abstract ( 487 )   PDF (1482KB) ( 96 )   Save
    BACKGROUND: The expression of miR-7 is down-regulated in various tumor tissues, including gastric cancer, and plays a major role in tumor suppression. It has been confirmed that miR-7 can affect a variety of cell biological functions, such as proliferation, apoptosis, migration, and invasion of gastric cancer cells. However, few studies have been conducted on the relationship between miR-7 and stem cell-like properties of gastric cancer cells, and the mechanism remains unclear.  
    OBJECTIVE: To investigate the effects of miR-7-5p on stem cell-like properties of human SGC-7901 gastric cancer cells.
    METHODS:  The gastric cancer cell line SGC-7901 was used as cell model. NC, miR-7-5p mimics, inhibitor NC and miR-7-5p inhibitor were transfected into cells, separately. The inverted fluorescent microscope was used to observe transfection efficiency at 48 hours post-transfection. The expression levels of miR-7-5p, Nanog and Sox2 mRNA were detected by RT-qPCR. Spheroid and soft-agar colony formation assays were performed to observe the abilities of spheroid and soft-agar colony formation, respectively. The proportion of CD24+CD44+ cell subsets was determined by flow cytometry.  
    RESULTS AND CONCLUSION: (1) The expression of miR-7-5p was significantly increased or decreased in SGC7901 cells after transfection of miR-7-5p inhibitor or mimics compared with inhibitor NC or NC group (P < 0.01). (2) The numbers of spheroid and soft-agar colony formation of SGC-7901 cells were decreased in the miR-7-5p mimics group than those in NC group (P < 0.05, P < 0.01), but increased in miR-7-5p inhibitor group than those in inhibitor NC group (P < 0.05, P < 0.01). (3) The proportion of CD24+CD44+ cells in the miR-7-5p mimics group was significantly lower than that in the NC group (P < 0.01). The proportion of CD24+CD44+ cells in miR-7-5p inhibitor group was significantly higher than those in inhibitor NC group (P < 0.01). (4) The mRNA expression levels of Nanog and Sox2 in the miR-7-5p mimics group were significantly lower than those in the NC group, and the mRNA expression levels of Nanog and Sox2 in the miR-7-5p inhibitor group were significantly higher than those in the inhibitor NC group (P < 0.05, P < 0.01). (5) miR-7-5p can inhibit spheroid and soft-agar colony formation abilities of gastric cancer cells, and reduce the proportion of CD24+CD44+ cell subsets in gastric cancer cells. The potential mechanism may be related to the regulation of the expression of stemness genes Nanog and Sox2.
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    Ciliary neurotrophic factor combined with forskolin and 3-isobutyl-1-methylxanthine induced muscle derived stem cells to differentiate into Schwann cells phenotype through cyclic adenosine monophosphate signaling pathway
    Gong Chao, Zhi Xiaodong, Zhang Yuqiang, Wang Chenliang, Wang Kang, Wang Wei
    2022, 26 (19):  2970-2977.  doi: 10.12307/2022.373
    Abstract ( 443 )   PDF (3742KB) ( 35 )   Save
    BACKGROUND: Schwann cells are the most ideal seed cells for peripheral nerve tissue engineering, but Schwann cells have many defects, so the research of cell therapy to repair peripheral nerve injury mainly focuses on other cells with Schwann cells characteristics, and Schwann cells-like cells have become the main source of choice for peripheral nerve injury repair.  
    OBJECTIVE: To investigate the method of differentiation of muscle derived stem cells into Schwann cells phenotypes induced by ciliary neurotrophic factor combined with forskolin and 3-isobutyl-1-methylxanthine and the correlation between the induction and the cyclic adenosine monophosphate signaling pathway, so as to lay the foundation for further application of muscle derived stem cells in peripheral nerve injury repair.
    METHODS:  Muscle derived stem cells were extracted from one-week old SD rats with mixed digestive enzymes. Dedifferentiation of muscle derived stem cells was induced by ciliary neurotrophic factor, and then the dedifferentiated muscle derived stem cells were induced by 3-isobutyl-1-methylxanthine. Cell morphology, immunofluorescence, CCK-8 assay, western blot assay, RT-qPCR and other techniques were used to identify and analyze muscle derived stem cells, dedifferentiated cells and Schwann cells-like cells. The expression of proteins related to cyclic adenosine monophosphate signaling pathway during dedifferentiation and Schwann cells-like differentiation was detected.  
    RESULTS AND CONCLUSION: (1) Cell immunofluorescence staining showed that primary cells taken from SD rats could be labeled with Desmin, a specific marker of muscle derived stem cells. CCK-8 assay results showed that the proliferation activity of P1-3 muscle derived stem cells gradually increased, and the proliferation activity of P3-8 muscle derived stem cells tended to stabilize. (3) Western blot assay showed that the expression of myogenic differentiation-related proteins p21 and MyoG decreased after ciliary neurotrophic factor induction, and the expression of cyclic adenosine monophosphate-related protein p-CREB increased. After 3-isobutyl-1-methylxanthine induction, the expression levels of Schwann cells markers S100β, GFAP, p75 and p-CREB increased, while cyclic adenosine monophosphate inhibitor SQ22536 could inhibit the effects of ciliary neurotrophic factor and 3-isobutyl-1-methylxanthine. (4) The RT-qPCR results were consistent with the western blot results; that was, the expression levels of S100β, GFAP and p75 mRNA increased after 3-isobutyl-1-methylxanthine induction, and SQ22536 could inhibit this effect. The results of CCK-8 assay showed that the cell activity was reduced after 3-isobutyl-1-methylxanthine induction. (5) Results concluded that ciliary neurotrophic factor combined with 3-isobutyl-1-methylxanthine can induce muscle derived stem cells to differentiate into Schwann cells phenotype, and the induction process activates the cyclic adenosine monophosphate signaling pathway.
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    Heterogeneity of chondrocytes derived from human ribs based on single-cell transcriptome sequencing
    Shi Hang, Li Jia, Liu Xia, Jiang Haiyue
    2022, 26 (19):  3011-3017.  doi: 10.12307/2022.379
    Abstract ( 542 )   PDF (2601KB) ( 61 )   Save
    BACKGROUND: Costal cartilage is an important source of cartilage in human tissues. It is often used as a source of seed cells for cartilage autograft and tissue engineering. As a powerful tool for analyzing cell heterogeneity, single-cell sequencing can conduct in-depth research on costal chondrocyte heterogeneity.  
    OBJECTIVE: Single-cell transcriptome sequencing is used to analyze the cell grouping of human costal cartilage tissue and the biological processes involved in each cell subgroup.
    METHODS:  A 31-year-old case of costal cartilage tissue discarded after a microtia reconstruction operation was obtained clinically and made into a primary cell suspension. Single-cell isolation was performed on the 10X Genomics platform. A single-cell RNA-seq library was constructed using Gel Bead Kit V3, and the library was analyzed by Illumina Novaseq6000 Sequencing and dimensionality reduction using Principal Component Analysis and  t-Distributed Stochastic Neighbor Embedding were used to obtain four subgroups of cells, and then to obtain marker genes for different subgroups of cells. GO and KEGG analyses were performed on the marker genes of each cell subgroup to analyze the biological processes that these genes may participate in.  
    RESULTS AND CONCLUSION: A total of 6 634 cells were obtained by sequencing, which met the quality control standards. The costal chondrocytes are divided into four cell subgroups, namely, hypertrophic chondrocyte population with COL10A1 and S100A2 as marker genes; chondrocyte population with BMP2 and COL2A1 as marker genes; and proliferative cells with FOS and JUN as marker genes; stem cell population with MYLK and CD146 as marker genes. The further division of costal chondrocytes into cell subgroups is helpful for in-depth understanding of the heterogeneity of cost chondrocytes, and has positive significance for its application as seed cells and understanding of diseases.
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    Effects of allogeneic bone marrow mesenchymal stem cells infusion on the expression of CXCL12/CXCR4 in the kidney of MRL/lpr lupus mice
    Cheng Mengwei, Tang Yu, Ma Cui, Shi Wei, Zheng Wenjuan, Qiu Yingying, Rui Jinbing, Wang Yanru
    2022, 26 (19):  3018-3023.  doi: 10.12307/2022.380
    Abstract ( 371 )   PDF (1861KB) ( 91 )   Save
    BACKGROUND: Chemokine CXCL12 and its receptor CXCR4 play a certain role in the pathogenesis of lupus nephritis, and it is of significance to explore the effect of bone marrow mesenchymal stem cells infusion on the expression of CXCL12/CXCR4 in lupus kidney for further study of the pathogenesis of lupus nephritis and the mechanism of bone marrow mesenchymal stem cells in the treatment of lupus nephritis.  
    OBJECTIVE: To investigate the effect of allogeneic bone marrow mesenchymal stem cell infusion on the expression of CXCL12/CXCR4 in the kidney of MRL/lpr lupus mice.
    METHODS:  Bone marrow mesenchymal stem cells of C57BL/6 mice were isolated and cultured, expanded to the third passage, and the cell concentration was 1×109 L-1. Totally 15 female MRL/lpr mice aged four to five weeks were selected and divided into MRL/lpr group (no tail vein infusion), PBS group (PBS injection at the end of 12 weeks), and bone marrow mesenchymal stem cell group (injection of bone marrow mesenchymal stem cells at the end of 12 weeks) (n=5 per group). An additional five C57BL/6 mice were selected as normal controls. Mice in each group were sacrificed at the end of 20 weeks of age. The expression of CXCL12 in peripheral blood plasma was detected by ELISA. The expression of CXCR4 on B lymphocyte surface in peripheral blood and kidney was analyzed by flow cytometry. The expression of CXCL12 in the kidney was demonstrated by immunohistochemistry. The pathological changes of the kidney tissue were observed by hematoxylin-eosin staining.  
    RESULTS AND CONCLUSION: (1) Compared with the C57BL/6 group, the expression of CXCL12 in peripheral blood plasma and kidney was increased, and the expression of CXCR4 on B lymphocyte surface in peripheral blood and kidney was also increased in the MRL/lpr group. (2) Compared with PBS group, the expression levels of CXCL12 in peripheral blood plasma and kidney of lupus mice were decreased, and CXCR4 expression levels on the surface of B lymphocytes in peripheral blood and kidney of lupus mice were similarly decreased in the bone marrow mesenchymal stem cell group. (3) Hematoxylin-eosin staining suggested that kidney injury was relieved in lupus mice after infusion of bone marrow mesenchymal stem cells. (4) It is concluded that there is abnormal expression of CXCL12/CXCR4 in the kidney of MRL/lpr lupus mice, and bone marrow mesenchymal stem cell infusion may play a therapeutic role by affecting the expression of CXCL12/CXCR4.
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    Implications of preclinical research on mesenchymal stem cells: relationship between cell function of mesenchymal stem cells and the JAK/STAT signaling pathway
    Zou Wanghui, Qian Nannan, Zhang Meng, Pang Qiming, Yang Yichun, Zhang Tao
    2022, 26 (19):  3048-3055.  doi: 10.12307/2022.385
    Abstract ( 499 )   PDF (2791KB) ( 37 )   Save
    BACKGROUND: Mesenchymal stem cells are a kind of pluripotent stem cells that have powerful functions in promoting tissue repair and immune regulation, and have become an important source of seed cells in the field of regenerative medicine. JAK/STAT signaling pathway, as a signaling pathway shared by many cytokines, can have a wide range of effects on the functions of mesenchymal stem cells themselves and their target cells.
    OBJECTIVE: To briefly describe the research progress of the relationship between JAK/STAT signaling pathway and mesenchymal stem cell function, provide an important reference for understanding the signaling pathway mechanism of mesenchymal stem cell function changes, and provide a theoretical reference for related mesenchymal stem cell preclinical research.
    METHODS: We searched relevant articles published from 2001 to 2021 in Wanfang database, CNKI, and PubMed. The key words were “mesenchymal stem cell, JAK/STAT, cell differentiation, immunomodulation” in Chinese and English. Finally, 48 articles were included for analysis. 
    RESULTS AND CONCLUSION: Mesenchymal stem cells can affect the JAK/STAT signaling pathway of target cells through extracellular secretion, and produce the effect of reversing the imbalanced microenvironment. In addition, the osteogenic differentiation, immunomodulation, adaptive changes, and homing effects of mesenchymal stem cells are all related to the JAK/STAT signaling pathway. (1) In terms of osteogenic differentiation, after cytokines activate JAK/STAT signaling pathway, mesenchymal stem cells can differentiate into osteoblasts. (2) In terms of immune regulation, JAK/STAT signaling pathway regulates mesenchymal stem cells, to express corresponding surface antigens or release cytokines, and promotes the proliferation of specific types of immune cells. (3) In terms of adaptive changes, JAK/STAT signaling pathway regulates mesenchymal stem cells in the in vivo or in vivo culture environment to have a high survival rate. (4) In terms of homing, the JAK/STAT signaling pathway regulates the migration of mesenchymal stem cells along the direction of target cells of chemokines.
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    Regulatory mechanism of exosomes in signal communication network of steroid induced avascular necrosis of the femoral head repair
    Wang Weiwei, Ou Zhixue, Zhang Xiaoyun, Li Shibin, Zhou Yi, Li Tong
    2022, 26 (19):  3056-3064.  doi: 10.12307/2022.386
    Abstract ( 478 )   PDF (1836KB) ( 110 )   Save
    BACKGROUND: The prevalence of steroid induced avascular necrosis of the femoral head is increasing year by year, and exosomes, as a major focus of current research, have highlighted the advantages and value of their applications in osteogenesis, angiogenesis, and bone tissue engineering.
    OBJECTIVE: To summarize the current research progress of exosomes in steroid induced avascular necrosis of the femoral head.
    METHODS: CNKI, Wanfang, VIP, Chinese Biomedical Literature Database, PubMed, Embase, Medline, and Web of Science were retrieved for relevant articles. Search terms were “exosomes, steroid induced avascular necrosis of the femoral head, mesenchymal stem cells, blood vessel, fat metabolism, tissue engineering, osteoblast, osteoclasts, synovial cells, chondrocytes, bone cells, platelet-rich plasma” in Chinese and English. The time was set from 2000 to 2021. Totally, 63 articles were screened according to the inclusion and exclusion criteria.
    RESULTS AND CONCLUSION: (1) Exosomes are used as transport vehicles to closely link the signal communication network formed between mesenchymal stem cells, endothelial cells, osteoblasts, osteoclasts, synovial cells, chondrocytes and osteocytes, and regulate osteogenesis and angiogenesis, which plays an important role in the repair of hormonal osteonecrosis of the femoral head. (2) It mainly regulates the proliferation, apoptosis, and differentiation of other cells in the signal communication network through Wnt/β-catenin and PI3K/AKT signal pathways, thereby improving the imbalance of the communication network caused by hormones. (3) This article preliminarily explained the role of exosomes in steroid induced avascular necrosis of the femoral head. However, because the current correlation studies mostly focus on the metabolic abnormalities of a single cell, the specific situation of the coupling mechanism has not been systematically clarified. (4) In addition, due to current technical limitations, the absolute safety of exosomes to organisms has not been scientifically verified. The extraction, identification, and storage of exosomes have high requirements on technology and equipment, and they can carry and continuously release exosomes. The research and development mechanism of biophilic materials is not yet mature, which limits the clinical promotion of exosomal therapy to a certain extent. (5) Based on the existing related mechanisms and bio-credit results, the research on the coupling mechanism of exosomes in steroid induced avascular necrosis of the femoral head bone tissue repair should be carried out; extraction, identification, and preservation techniques of exosomes should be improved to reduce certain experimental errors, so as to avoid some contradictory experimental conclusions and further analyze the relevant components in different sources of exosomes, which can provide a certain prerequisite and basis for clinical applications. (6) Based on the existing relevant experimental basis, in the future, it is necessary to continue to study the mechanism of the related target cells in the exchange network of exosomes combined with repair and the corresponding bone tissue biomaterials.
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    Important role of exosomes-mediated hypoxia-related signaling pathways in the occurrence and progression of diseases
    Gu Xia, Wang Pingyi, Zhao Wanhua, Lin Yushi, Li Yimei, Li Wenhua
    2022, 26 (19):  3065-3070.  doi: 10.12307/2022.387
    Abstract ( 488 )   PDF (1469KB) ( 32 )   Save
    BACKGROUND: At present, exosomes have made remarkable progress as new biomarkers for disease diagnosis in hypoxia-related diseases and tumor diseases, and have become potential players in the prevention and treatment of hypoxia-related diseases.
    OBJECTIVE: To explore the mechanism of exosomes interference with hypoxia-related signaling pathways to change the occurrence and development of hypoxia-related diseases at the molecular level, so as to provide a basis for the research and treatment of hypoxia-related diseases.
    METHODS: Using the search terms of “hypoxia, exosomes, signal pathway” in Chinese and English, articles published from January 2016 to May 2021 were retrieved from PubMed, Medline, CNKI, and Wanfang databases. Finally, 56 articles were included for analysis. 
    RESULTS AND CONCLUSION: (1) In hypoxic environment, exosomes are closely related to some hypoxia-related signaling pathways. Exosomes-mediated hypoxia signaling pathways may be involved in altering the pathogenesis of hypoxia-related diseases and tumor. (2) Through hypoxia inducible factor, phosphatidylinositol 3-kinase/serine/threonine kinase, nuclear factor κB, transforming growth factor β and other hypoxia-related signaling pathways, exosomes released by donor cells, carrying their information and accepted by recipient cells, mediate important physiological and pathological processes,  such as immune response, cell proliferation, migration, angiogenesis, and tumor invasion in diseases. (3) In hypoxia-related inflammatory diseases, exosomes can induce the activation of the above-mentioned hypoxia signaling pathways to reduce inflammatory damage. (4) However, in tumor diseases, exosomes mediate the activation of above hypoxia-related signaling pathways, which accelerate the angiogenesis of tumor sites and promote the invasion and metastasis of tumor cells, resulting in the progression of tumor. This effect may be associated with the cell origin of exosomes. Further exploration is needed to understand its specific regulatory mechanism.
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    Application of mesenchymal stem cells and exosomes in liver regeneration
    Bai Jiameng, Liu Guangwei, Xie Lu, Mao Yaoyao, He Huichang, Wang Chunjing
    2022, 26 (19):  3071-3077.  doi: 10.12307/2022.388
    Abstract ( 594 )   PDF (1155KB) ( 36 )   Save
    BACKGROUND: Many studies have shown that mesenchymal stem cells have broad application prospects in the field of regenerative medicine. In addition to mesenchymal stem cells themselves, exosomes derived from mesenchymal stem cells have also become the focus of researchers’ attention, which brings new ideas for the treatment of diseases.
    OBJECTIVE: To review the application, challenge and prospect of mesenchymal stem cells and their exosomes in the field of liver regeneration, and to further understand their therapeutic mechanism.
    METHODS: With the search terms of “mesenchymal stem cells, MSCs, exosomes, liver, regenerate”, relevant articles published in PubMed database, Wanfang database and CNKI database were searched. Through screening and sorting, the articles unrelated to the research content, repetitive studies and early published articles were excluded. Finally, 85 articles were reserved for review. 
    RESULTS AND CONCLUSION: Mesenchymal stem cells and their exosomes can play a protective role in the liver and delay the progress of the disease. The specific mechanisms include reducing hepatocyte apoptosis, regulating autophagy, improving inflammatory response, improving oxidative stress, inhibiting fibrosis, and promoting angiogenesis, which can be used as a new direction for the treatment of liver injury related diseases.
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    Effect and mechanism of mesenchymal stem cell-related long non-coding RNA on cell proliferation and apoptosis
    Qiu Hanke, Zhang Fei, Peng Wuxun
    2022, 26 (19):  3078-3083.  doi: 10.12307/2022.389
    Abstract ( 433 )   PDF (1088KB) ( 95 )   Save
    BACKGROUND: Mesenchymal stem cells have been widely used in the field of medical regeneration, and how to improve their therapeutic effect is the current research focus. Long-chain non-coding RNA is involved in the occurrence and development of many diseases. Some studies have shown that mesenchymal stem cell-related long-chain non-coding RNA is involved in the regulation of cell proliferation and apoptosis, but its specific role and mechanism are not completely clear. Understanding its role and mechanism may provide new strategies to improve the application effect of mesenchymal stem cells.
    OBJECTIVE: To review the role and mechanism of mesenchymal stem cell-related long-chain non-coding RNA in cell proliferation and apoptosis.
    METHODS: CNKI and PubMed were retrieved using “mesenchymal stem cells, long non-coding RNA, proliferation, apoptosis” as Chinese and English search words. After excluding outdated and repetitive views, the retrieved articles were sorted out, and 74 articles were selected for review. 
    RESULTS AND CONCLUSION: (1) Long non-coding RNA is involved in regulating the proliferation and apoptosis of mesenchymal stem cells. (2) Long non-coding RNA associated with mesenchymal stem cells can regulate the proliferation and apoptosis of host cells. (3) The main mechanisms of long non-coding RNA are as follows: competitive endogenous RNA as micro-RNA, directly affecting key transcription factors, and enhancing related signal pathways. (4) The long non-coding RNA associated with mesenchymal stem cells may be a new strategy to improve the application effect of mesenchymal stem cells.
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    Effect of mesenchymal stem cells on negative regulation of immune response of myeloid-derived suppressor cells
    Min Keting, Zhang Yiguo, Yang Hao, Lü Xin
    2022, 26 (19):  3084-3089.  doi: 10.12307/2022.390
    Abstract ( 571 )   PDF (1108KB) ( 78 )   Save
    BACKGROUND: Myeloid-derived suppressor cells are a heterogeneous group of cells derived from bone marrow, which can inhibit the function of T cells and exert immunosuppressive effect. Mesenchymal stem cells are pluripotent stem cells, which can inhibit innate and adaptive immune responses. Myeloid-derived suppressor cells and mesenchymal stem cells have many similarities in immunosuppressive function, which can be related to each other in tumor, inflammation and transplantation.
    OBJECTIVE: To summarize the mechanisms of action based on myeloid-derived suppressor cells and the effect of mesenchymal stem cells on the negative regulatory effect of immune response in myeloid-derived suppressor cells.
    METHODS: A computer search of the Web of Science Core Collection database was conducted with key words of “myeloid-derived suppressor cells”, “mesenchymal stem cells”, “stem cells”. Finally, 49 papers were included for review. 
    RESULTS AND CONCLUSION: Myeloid-derived suppressor cells play an important immunosuppressive role in vivo by secreting arginase-1, inducible nitric oxide synthase, and indoleamine 2,3-dioxygenase. Myeloid-derived suppressor cells and mesenchymal stem cells interact through different mechanisms in the treatment of autoimmune diseases, organ transplantation, inflammatory infections, tumors and other diseases, causing tumor cells to evade immune surveillance and promoting further tumor progression. In non-tumor diseases, myeloid-derived suppressor cells play a certain benign regulatory role, weakening the body’s own immune response and improving clinical symptoms.
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    Mechanism of mesenchymal stem cell transplantation in the treatment of osteoporosis
    Tang Zhihong, Duan Hao, Zhong Zongyu, Wang Weizhou, Chen Yongcheng, Li Xiaozhuang, Wang Yanghao, Liu Zhui, He Fei
    2022, 26 (19):  3090-3094.  doi: 10.12307/2022.391
    Abstract ( 655 )   PDF (1055KB) ( 59 )   Save
    BACKGROUND: For the treatment of osteopenia, cell therapy is a hot spot in current research. How to select seed cells and understand its treatment mechanism will help promote the clinical application of mesenchymal stem cells.  
    OBJECTIVE: To summarize the research progress of mesenchymal stem cells in the treatment of osteoporosis in recent 10 years.
    METHODS:  With “osteoporosis, mesenchymal stem cells” as Chinese and English keywords, CNKI, Wanfang database and PubMed database were searched respectively. The search time was set from January 2010 to January 2021, and 158 related articles were initially found. After reading and analyzing, 63 articles were selected for summary.  
    RESULTS AND CONCLUSION: Mesenchymal stem cells from different sources can produce therapeutic effects on different types of osteoporosis. However, its therapeutic effect is affected by homing efficiency, and its therapeutic mechanism involves many aspects, such as osteogenesis and angiogenesis. This makes mesenchymal stem cells have great advantages over traditional drugs in the treatment of osteoporosis. However, the adverse effects of teratogenicity and tumorigenesis and the ethical issues involved are still the main factors hindering its clinical application.
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    Prospects and clinical transformation value on the application of dental follicle stem cells in the regeneration and repair of teeth and periodontal tissue
    Meng Shengzi, Liu Rong, Luo Yaxin, Bi Haoran, Chen Xiaoxu, Yang Kun
    2022, 26 (19):  3095-3099.  doi: 10.12307/2022.392
    Abstract ( 1047 )   PDF (1178KB) ( 45 )   Save
    BACKGROUND: As a kind of dental mesenchymal stem cells, dental follicle stem cells have considerable application prospect and clinical transformation value in stem cell therapy and tissue engineering because of their excellent characteristics.
    OBJECTIVE: To review the basic characteristics of dental follicle stem cells and their latest progress in the field of regeneration and repair of tooth and periodontal complex tissue structure.
    METHODS: The key words were “dental follicle stem cell, regeneration, tooth, bone, periodontal tissue, tissue engineering, review” in Chinese and English. PubMed, Sciencedirect, Medline, CBM, CNKI, and other databases were retrieved in articles published from 2010 to 2021. Finally, 61 articles were included for analysis and discussion. 
    RESULTS AND CONCLUSION: As dental mesenchymal stem cells, dental follicle stem cells have great application value in the field of oral regenerative medicine, and they have the characteristics of rich sources, multi-directional differentiation, and low immunogenicity. At present, dental follicle stem cells are actively used in the regeneration of periodontal tissue, tissue engineering biological root reconstruction and alveolar bone repair. Their therapeutic potential in other tissue injuries and immune system diseases has been continuously explored in recent years. However, before more in-depth clinical application, how to better regulate the functional mechanism of transplanted dental follicle stem cells and control the immune system response, in order to further optimize the construction methods of teeth and periodontal tissue, is worthy of in-depth research and discussion.
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    Assessment of in vitro 3D large-scale hepatocyte proliferation culture system and automated and intelligent bioreactor systems
    Li Ke, Zhang Guanghao, Zhang Cheng, Yang Jiayi, Wu Changzhe, Huo Xiaolin
    2022, 26 (19):  3100-3107.  doi: 10.12307/2022.393
    Abstract ( 690 )   PDF (1286KB) ( 156 )   Save
    BACKGROUND: How to obtain sufficient quantity and quality of hepatocytes in vitro is the core problem to be solved urgently in the clinical application of bioartificial liver.
    OBJECTIVE: To summarize the main research contents of the in vitro 3D large-scale expansion culture system of hepatocytes, summarize the current main sources of seed cells, 3D culture methods, bioreactor system, and the progress and limitations of real-time online monitoring of key indicators of the culture process, and prospects for the further development of automated and intelligent bioreactor systems.
    METHODS: The first author searched the Web of Science core database, ScienceDirect, EI, PubMed, and CNKI databases. The English and Chinese search terms were “hepatocyte, 3D culture, proliferate, bioreactor system, monitor and control”. The literature search time range was from January 2005 to March 2021. The types of articles included original research works, reviews and meta-analysis. Totally, 93 papers were selected for analysis. 
    RESULTS AND CONCLUSION: (1) Researches on liver seed cell sources, 3D culture methods, bioreactor system construction, and real-time online monitoring methods for key biochemical indicators have all made progress, laying a solid foundation for the further construction of a large-scale in vitro 3D hepatocyte culture system. (2) Human hepatocarcinoma cell lines, immortalized hepatocytes, stem cell differentiation and other hepatocytes can be cultured and proliferated in vitro and express liver function. Among them, hepatocyte-like cells obtained from stem cell differentiation and direct reprogramming have cells similar to mature liver cells morphology, function, and gene expression profile will have greater application prospects in the future. (3) 3D suspension culture has excellent performance in terms of culture density and mass transfer efficiency, and has the advantages of easy amplification, convenient inoculation, and convenient access. It is the main development direction of in vitro 3D culture of hepatocytes. (4) Although the existing bioreactor system can realize in vitro culture and expansion of hepatocytes, it has a low degree of automation and lacks a real-time online detection method for key biochemical indicators. In addition, the current degree of mutual integration of these several aspects of research also restricts the progress of the in vitro 3D large-scale culture system of hepatocytes. (5) The future research is to combine the growth characteristics of liver seed cells from different sources, select suitable culture methods, and establish a real-time online monitoring method for key parameters during the culture process, so as to construct a highly automated and intelligent bioreactor system to achieve in vitro scale of liver cells large-scale preparation.
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    Function of oligodendrocytes and demyelinating disease
    Song Shengjiao, Li Juan, Wu Wencheng, Xiao Yun, Liao Baoying, Li Xing
    2022, 26 (19):  3108-3116.  doi: 10.12307/2022.394
    Abstract ( 881 )   PDF (1349KB) ( 206 )   Save
    BACKGROUND: Demyelination diseases are a disease that presents loss of myelin, and relative light damage to neuronal cell body and axon. Under normal physiological conditions, the body will spontaneously carry out remyelination after demyelination. However, under pathological conditions, this process can be inhibited by many factors, resulting in incompletion or failure of myelin sheath regeneration, making demyelination development, and the diseases can continue to aggravate.
    OBJECTIVE: To emphasize the critical role of oligodendrocytes in the process of remyelination, how to develop drugs and cell-based demyelinating disease drugs from the perspective of oligodendrocytes so as to provide a new approach for drug development of demyelinating diseases.
    METHODS: Databases of PubMed, GeenMedical, and CNKI were searched for the articles regarding oligodendrocytes and demyelinating diseases or involving oligodendrocyte precursor cells, oligodendrocyte-related functions, and remyelination published from the inception to May 1, 2021. The key words were “oligodendrocyte, demyelinating diseases” in English and Chinese. Totally 142 articles were included. 
    RESULTS AND CONCLUSION: (1) The role of oligodendrocytes in demyelinating diseases is essential for remyelination. In inflammatory microenvironments, the function of oligodendrocytes can be impaired and damage axonal conduction. Therefore, maintaining the function of oligodendrocytes in the central nervous system is crucial to treat demyelinating diseases. (2) At present, new treatment strategies for demyelinating diseases are endless, mainly to prevent inflammation. For example, bioinformatics technology is used to screen available small molecule compounds. Alternatively, some drugs approved by Food and Drug Administration are developed to screen subjects. Or drugs have been developed that target internal and external signals at different stages of myelin regeneration. Furthermore, there are also cell therapies for transplantation of central nervous system stem cells with the ability to differentiate into oligodendrocytes to the affected area. The current research has its various treatment entry points, and the development of low-cost, low side effects, high drug efficacy, and high-efficiency treatment strategies also face arduous challenges.
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