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    08 September 2020, Volume 24 Issue 25 Previous Issue    Next Issue
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    Effect of bone marrow mesenchymal stem cells on microglial activation after optic nerve injury in rats
    Luan Shuangyu, Zeng Liang, Chen Bin, Tian Wei, Yan Nan, Chen Xi, Zhang Shuo, Wang Zhengdong
    2020, 24 (25):  3937-3942.  doi: 10.3969/j.issn.2095-4344.2101
    Abstract ( 431 )   PDF (898KB) ( 64 )   Save

    BACKGROUND: Traumatic optic nerve injury is an important cause of vision loss, and the treatment methods are relatively limited. In order to find a better treatment method, this experiment started from the direction of microglia. Under neuropathological conditions, activation of microglia can maintain the stability of the central nervous system, but excessive activation of microglia can produce a large number of inflammatory factors that progressively aggravate the damage.

    OBJECTIVE: To investigate the activation of microglia after optic nerve injury and the effect of bone marrow mesenchymal stem cells (BMSCs) on the overexpression of microglia.  

    METHODS: There were 18 Sprague-Dawley rats, 8 weeks of age, which were divided into BMSCs transplantation group, model group and sham operation group, with 6 rats in each group. In the model group and BMSCs transplantation group, the rat’s left eye was selected to separate the retina and optic nerve after the optic clamping of the optic nerve. The sham operation group only separated the retina and optic nerve with no clamping. In the BMSCs transplantation group, the left eye vitreous body was injected with quantitative passage 3 BMSCs (1×108 cells, 2 μL) immediately after the injury. While in the model group and sham operation group, the same amount of PBS was injected into the vitreous body. All the rats were sacrificed at 15 days postoperatively. After perfusion and fixation, the retina with optic nerve was taken for hematoxylin-eosin staining and immunohistochemical detection.

    RESULTS AND CONCLUSION: The expression levels of Ox-42 and tumor necrosis factor α were significantly higher in the model group than in the sham operation group (P < 0.05), while the expression of Ox-42 and tumor necrosis factor α in the optic nerve and retina in the BMSCs group was decreased and almost the same to that in the sham operation group. Therefore, excessive activation of microglia is associated with optic nerve injury, and BMSCs can inhibit the excessive activation of microglia and release of inflammatory factors, thus protecting the retina and optic nerve from traumatic injury to some extent. 

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    Cytotoxicity assessment of bone marrow mesenchymal stem cells-cuttlebone composite scaffold  
    Peng Ya, Qin Yu, Yi Hongcheng, Gu Chunsong, Li Lili
    2020, 24 (25):  3943-3946.  doi: 10.3969/j.issn.2095-4344.2102
    Abstract ( 401 )   PDF (565KB) ( 60 )   Save

    BACKGROUND: Repair materials for bone tissue engineering should hold good biocompatibility and degradability. There are various related studies, but the Chinese medicine composite cellular bioscaffolds are little reported.

    OBJECTIVE: To detect the in vitro cytotoxicity of rabbit bone marrow mesenchymal stem cells-cuttlebone bioscaffold based on the Biological Evaluation of Medical Device, and assess its cytotoxicity level in order to provide the theoretical support for its clinical application.

    METHODS: Bone marrow mesenchymal stem cells-cuttlebone bioscaffold extract was prepared according to an ISO standard — material area: extraction medium volume = 3-6 cm2:1 mL. L-929 cell suspension was prepared, and the cells were then cultured with a density of 1×107/L. There were three groups: positive group (DMEM medium containing phenol), experimental group (material extract), and negative group (DMEM culture medium). The absorbance value of L-929 cells was detected by MTT assay after 24, 48 and 72 hours of culture. The relative proliferation rate of cells was then calculated and the toxicity level was valued in each group.

    RESULTS AND CONCLUSION: The absorbance values in the experimental, negative and positive groups were not exactly same at different time points (P=0.000 < 0.01). The absorbance values in the experimental and negative groups were significantly higher than those in the positive group (P < 0.01).The cytotoxicity of bone marrow mesenchymal stem cells-cuttlebone bioscaffold was grade 1. To conclude, the bone marrow mesenchymal stem cells-cuttlebone bioscaffold has no obvious toxic effects, and meets the requirements of biomaterial application.

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    Protective effect of human umbilical cord blood mesenchymal stem cells on the rat’s blood-brain barrier after traumatic brain injury
    Chen Jianglong, Shi Xinyu, Cheng Jun, Ye Yichao, Zhang Zhenwen, Li Xiaohong, Sun Hongtao
    2020, 24 (25):  3947-3952.  doi: 10.3969/j.issn.2095-4344.2109
    Abstract ( 401 )   PDF (864KB) ( 380 )   Save

    BACKGROUND: Human umbilical cord mesenchymal stem cells play a vital role in the repair of the blood-brain barrier after traumatic brain injury.

    OBJECTIVE: To investigate the protective effect of human umbilical cord blood mesenchymal stem cell transplantation on the blood-brain barrier after traumatic brain injury in rats and its possible mechanism.  

    METHODS: Sixty Sprague-Dawley rats were randomly divided into sham operation group, injury control group (model group), cell transplantation group and Sunitinib group, with 15 rats in each group. Traumatic brain injury model was established by improved hydraulic impact method in all the groups except for the sham operation group. Rats in the sham operation group and model group were injected with 1 mL of normal saline, and those in the cell transplantation group were injected with 1 mL of 2×109 /L human umbilical cord blood mesenchymal stem cells. The injection was done via the tail vein at 0.5, 24, and 48 hours after modeling. In the Sunitinib inhibitor group, the rats were given oral PDGFR-β pathway inhibitor, Sunitinib (80 mg/kg), from 1 day before modeling until being executed. Three days after modeling, the water content in brain tissue was measured by dry-wet specific gravity method, the permeability of the blood-brain barrier was measured by Evans blue method, expression of GFAP and vWF was observed by immunofluorescence staining and the expression of blood-brain barrier related proteins and PDGFR-β pathway proteins was detected by western blot method. 

    RESULTS AND CONCLUSION: Compared with the sham operation group, the brain water content of the model group increased significantly (P < 0.05), while that of the cell transplantation group was significantly lower than that of the model group (P < 0.05). The Evans blue content in the model group was significantly higher than that in the sham operation group (P < 0.05), while the Evans blue content in the cell transplantation group was significantly lower than that in the model group (P < 0.05). Compared with the sham operation group, the expression of vWF and GFAP increased significantly in the model group (P < 0.05), while compared with the model group, the expression was significantly reduced in the cell transplantation group (P < 0.05). Western blot showed that ZO-1, Oclaudin-5, and PDGFR-β protein expressions in the model group were significantly lower than those in the sham operation group (P < 0.05), while these expressions were significantly increased in the cell transplantation group as compared with the model group (P < 0.05). To conclude, intravenous injection of human umbilical cord mesenchymal stem cells through the tail ein can reduce the permeability of blood-brain barrier and play a neuroprotective role in rats with traumatic brain injury. Its possible mechanism is related to the promotion of PDGFR-β expression in the injured area.

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    Extracellular matrix improves antioxidant capacity of human umbilical cord stem cells  
    Zhao Yilang, Liu Tao, Yang Huilin, He Fan
    2020, 24 (25):  3953-3958.  doi: 10.3969/j.issn.2095-4344.2086
    Abstract ( 483 )   PDF (794KB) ( 73 )   Save

    BACKGROUND: Extracellular matrix has been shown to improve cell proliferation and reduce intracellular reactive oxygen species levels. However, there is little research on whether extracellular matrix can enhance the antioxidant capacity of umbilical cord stem cells to enhance their application in regenerative medicine and tissue engineering.

    OBJECTIVE: To investigate the effect of extracellular matrix on umbilical cord stem cell proliferation, antioxidant and osteogenic capacity.

    METHODS: The umbilical cord stem cells were divided into four groups. In the polystyrene group, the umbilical cord stem cells were cultured with ordinary polystyrene culture plate without other special treatment. In the extracellular matrix group, the umbilical cord stem cells were cultured with extracellular matrix without other special treatment. In the polystyrene + hydrogen peroxide group, the umbilical cord stem cells were cultured with polystyrene plate and pretreated with 200 μmol/L hydrogen peroxide for 2 hours. In the extracellular matrix + hydrogen peroxide group, umbilical cord stem cells were cultured with extracellular matrix and pretreated with 200 μmol/L hydrogen peroxide for 2 hours. The cells were pretreated with 200 μmol/L hydrogen peroxide for 2 hours. Proliferation capacity of umbilical cord stem cells was detected by CCK-8 assay. The cells were cultured for 72 hours after hydrogen peroxide pretreatment for 2 hours. The antioxidant capacity of umbilical cord stem cells was detected by flow cytometry and qRT-PCR. After 2 hours of hydrogen peroxide pretreatment, the cells were induced to differentiate into osteoblasts for 14 days. The osteogenic capacity of umbilical cord stem cells was detected by alizarin red staining and qRT-PCR.

    RESULTS AND CONCLUSION: The absorbance values of extracellular matrix group and extracellular matrix + hydrogen peroxide group were higher than that of polystyrene group and polystyrene + hydrogen peroxide group, respectively. The levels of reactive oxygen species in the polystyrene + hydrogen peroxide group and the polystyrene group were higher than those in the extracellular matrix group and the extracellular matrix + hydrogen peroxide group, respectively (P < 0.05). The expression levels of antioxidant enzyme-related genes SOD2 and CAT in the extracellular matrix group and extracellular matrix + hydrogen peroxide group were significantly higher than those in the polystyrene group and the polystyrene + hydrogen peroxide group, respectively (P < 0.05). The expression of bone related genes COL-1, RUNX2, OCN, and OSTERIX was highest in the extracellular matrix group, followed by the extracellular matrix + hydrogen peroxide group, and lowest in the polystyrene + hydrogen peroxide group; there was significant difference between the groups (P < 0.05). The results show that extracellular matrix can increase the proliferation capacity, antioxidant capacity and osteogenic differentiation potential of umbilical cord stem cells. It is a method for in vitro amplification and culture of cells with wide application prospects.

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    Canine adipose-derived mesenchymal stem cells and their exosomes in the repair of gentamicin-induced renal tubular epithelial cell injury 
    Lin Jiaying, Chen Shuyi, Chen Shengfeng, Wang Bingyun, Chen Zhisheng, Liu Canying, Bai Yinshan, Ji Huiqin, Xie Shiting
    2020, 24 (25):  3959-3965.  doi: 10.3969/j.issn.2095-4344.2089
    Abstract ( 456 )   PDF (922KB) ( 61 )   Save

    BACKGROUND: Canine kidney injury is characterized by the apoptosis and necrosis of renal tubular epithelial cells. Recent developments in mesenchymal stem cells and their exosomes research have shown great promise for the treatment of kidney injury in humans, rats and mice, but little research has been done on dogs.

    OBJECTIVE: To investigate the effects of canine adipose-derived mesenchymal stem cells and their exosomes on canine renal tubular epithelial cell injury induced by gentamicin in vitro.

    METHODS: Canine renal tubular epithelial cells were treated by 5 mmol/L gentamicin sulfate. Subsequently, canine adipose-derived mesenchymal stem cells and their conditional medium and exosomes were co-cultured with damaged canine renal tubular epithelial cells respectively. After 24 and 48 hours, the cell proliferation activity of each group was measured by cell counting kit-8 method, and the apoptosis rate of each group was detected by flow cytometry. Finally, Q-PCR was used to further reveal the effects of canine adipose-derived mesenchymal stem cell exosomes on PCNA, Bcl-2 and Bax genes in these cells.

    RESULTS AND CONCLUSION: Canine adipose-derived mesenchymal stem cells, their conditioned media, and exosomes could significantly promote proliferation and reduce apoptosis in damaged canine renal tubular epithelial cells (P < 0.05). Among them, canine adipose-derived mesenchymal stem cell exosomes worked best, which could significantly increase the expression of PCNA and Bcl-2 genes in damaged canine renal tubular epithelial cells (P < 0.05). These results suggest that canine adipose-derived mesenchymal stem cells can repair the canine renal tubular epithelial cell damage induced by gentamicin through their exosomes.

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    Transplantation of human umbilical cord blood mesenchymal stem cells in the repair of hematopoietic injury in bone marrow

    Gao Kunli, Xing Hongyun, Bian Tierong, Han Liying
    2020, 24 (25):  3966-3972.  doi: 10.3969/j.issn.2095-4344.2103
    Abstract ( 461 )   PDF (1456KB) ( 166 )   Save

    BACKGROUND: A large number of studies mainly concern the proliferation effect of mesenchymal stem cells on hematopoietic stem cells in vitro and that bone marrow mesenchymal stem cell transplantation can reduce the death of hematopoietic cells caused by irradiation, increase the survival of bone marrow cells and repair hematopoiesis, while few of them investigate the repair of human umbilical cord blood mesenchymal stem cells transplantation on bone marrow hematopoiesis injury.  

    OBJECTIVE: To explore the repair of hematopoietic microenvironment of bone marrow by human umbilical cord blood mesenchymal stem cells.

    METHODS: Male BALB/c mice were randomly divided into three groups. The mice in experimental group and control group were irradiated with total dose of 6-Gy X-ray to establish a mouse model of bone marrow hematopoietic injury. The normal group contained untreated normal mice. In the experimental group, CM-DiL labeled human umbilical cord blood mesenchymal stem cells were injected into the tail vein of each mouse at 5×106 (0.2 mL). The control group and the normal group received normal saline 0.2 mL through the tail vein. The peripheral blood hematology and bone marrow hematopoietic microenvironment repair were observed at 1, 5, 7, 14 and 21 days after cell transplantation.

    RESULTS AND CONCLUSION: Peripheral blood condition: At 1, 5 and 7 days after transplantation, the leucocyte, platelet, erythrocyte count and hemoglobin concentration in the experimental group and control group decreased progressively compared with the normal group. The most obvious decrease occurred on day 7. The trilineage recovered on day 14 after transplantation, basically returned to normal on day 21 after transplantation. Compared with the experimental group, the decrease of the trilineage in the control group was more obvious. The recovery was obvious faster in the experimental group than in the control group on day 14 after transplantation. Bone marrow smears: Bone marrow smears showed that the hematopoietic function was inhibited in the experimental group and the control group at 1, 5, 7, and 14 days after transplantation, especially on day 7. Bone marrow proliferation recovered on day 14 after transplantation. It was better in the experimental group than in the control group. On day 21 after transplantation, the hematopoietic function of bone marrow of mice in the experimental group and the control group recovered, and there was no difference between the experimental group and the control group compared with the normal group. Bone marrow pathological section: Bone marrow pathological sections showed that at 1, 5, 7, and 14 days after transplantation, the hematopoietic function of bone marrow in the experimental group and the control group was inhibited. On day 14 after transplantation, the bone marrow hematopoietic function of the experimental group and the control group began to recover, but the bone marrow proliferation of the experimental group was better than that of the control group. On day 21 after transplantation, there was no difference in the bone marrow proliferation between the experimental and the control groups and the normal group. The results suggested that human umbilical cord blood mesenchymal stem cells can promote the recovery of hematopoietic function of bone marrow. 

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    Osteogenesis of bone marrow mesenchymal stem cells on hydroxyapatite/icariin/poly(lactic-co-glycolic acid) scaffolds

    Wang Dexin, Xu Zhanwu, Pei Guoxian
    2020, 24 (25):  3974-3980.  doi: 10.3969/j.issn.2095-4344.2083
    Abstract ( 391 )   PDF (775KB) ( 74 )   Save

    BACKGROUND: Bone tissue engineering has provided a novel ideal for treating bone defects in clinic. This study is the first to combine traditional Chinese medicine with the nanostructures of tissue-engineered scaffolds in order to explore and construct a new bone tissue substitute material for the treatment of bone defects.

    OBJECTIVE: To investigate the osteogenic activity of icariin (ICA)/hydroxyapatite (HA)/poly(lactic-co-glycolic acid) (PLGA) composite scaffolds.

    METHODS: A HA/PLGA composite scaffold was prepared by physical blending of HA and PLGA, and was then soaked in ICA solution of different concentrations to obtain the HA/ICA/PLGA scaffold. Rabbit bone marrow mesenchymal stem cells were used to evaluate the cell adhesion, proliferation, osteogenesis and cytotoxicity of the composite scaffold. The cell adhesion, proliferation and cytotoxicity were detected by MTT method. The activities of alkaline phosphatase and osteocalcin were detected by ELISA. The expression levels of osteogenic genes and proteins were detected by fluorescence quantitative PCR and western blot assay, respectively.

    RESULTS AND CONCLUSION: Adding appropriate amount of HA into PLGA could improve the mechanical strength of the scaffold, and 10% HA had the best effect with tensile strength of (1.67±0.37) MPa, and compression modulus of (4.17±1.62) MPa, and nanostructure would be formed on the surface of the scaffold. The nanostructure could promote the adhesion of bone marrow mesenchymal stem cells on the surface of the scaffold. ICA did not affect the proliferation of bone marrow mesenchymal stem cells on the composite scaffold. However, the HA/PLGA composite scaffold soaked in 1.00 µmol/L ICA aqueous solution had the optimal osteogenic differentiation function, and the expression levels of alkaline phosphatase, osteocalcin, osteogenic related genes and proteins (Runx-2 and COL I) were increased. The ICA/HA/PLGA scaffold had no cytotoxicity. These results suggest that HA (10%)/ICA (1.00 µmol/L)/PLGA scaffold has good mechanical properties, osteogenesis and biocompatibility, which has the potential to be a favorable scaffold for bone tissue engineering.

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    Co-transplantation of adipose mesenchymal stem cells and endothelial progenitor cells in ulcerative colitis mice  

    Hou Xiaolin, Liang Jun, Yang Cheng, Cui Meihua
    2020, 24 (25):  3981-3987.  doi: 10.3969/j.issn.2095-4344.2110
    Abstract ( 399 )   PDF (890KB) ( 86 )   Save

    BACKGROUND: Mesenchymal stem cell transplantation has been proved to be effective for ulcerative colitis, while the effect of endothelial progenitor cells in ulcerative colitis treatment is still unknown. They are both promising cells for tissue engineering, which can be used for cell transplantation.

    OBJECTIVE: To explore whether co-transplantation of endothelial progenitor cells and adipose mesenchymal stem cells can relieve ulcerative colitis in a mouse model.

    METHODS: C57BL/6J mice were randomly divided into six groups (n=24 per group): co-transplantation group, mesenchymal stem cell transplantation group, endothelial progenitor cell transplantation group, glucocorticoid treatment group, transplantation control group and normal control group. Murine ulcerative colitis model was established in all groups except for the normal control group. At 7 and 10 days after modeling, transplantation groups were respectively injected via tail vein with adipose mesenchymal stem cells and/or endothelial progenitor cells, glucocorticoid or PBS. Mice were sacrificed at 12 days after modeling. Colon length, disease activity index, histological score and the serum level of tumor necrosis factor-α were compared between groups.

    RESULTS AND CONCLUSION: Treatment with glucocorticoid was significantly effective for ulcerative colitis relative to the transplantation control group (P < 0.05). Adipose mesenchymal stem cells were proved to have better effects than glucocorticoids in the murine ulcerative colitis model (P < 0.05). No significant differences were found between endothelial progenitor cell transplantation group and transplantation control group (P > 0.05). Co-transplantation of adipose mesenchymal stem cells and endothelial progenitor cells was better than the other treatments, which significantly improved the shortening of the colon, disease activity index, histological score, and serum level of tumor necrosis factor-α.

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    Lentivirus-mediated P75 neurotrophin receptor silencing combined with nerve growth factor overexpression promotes proliferation of rat bone marrow mesenchymal stem cells 

    Wang Ning, Chen Junyi, Zhu Lunjing, Duan Jiangtao, Wang Ye, Li Zhijun, Bei Chaoyong
    2020, 24 (25):  3988-3993.  doi: 10.3969/j.issn.2095-4344.2099
    Abstract ( 421 )   PDF (819KB) ( 72 )   Save

    BACKGROUND: P75 Neurotrophin receptor (P75NTR) is one of the receptors for nerve growth factor (NGF). P75NTR plays a dual role in promoting proliferation or apoptosis in various cell tissues, and is highly expressed at fracture nonunion sites. However, excessive NGF can shut down P75NTR receptor, thereby saving damaged cells. Therefore, the study regarding co-transfection of silenced P75NTR and NGF overexpression is of great significance for the proliferation of bone marrow mesenchymal stem cells and provides new ideas for clinical treatment of fracture nonunion.

    OBJECTIVE: To observe the effect of lentivirus-mediated silencing of P75NTR combined with NGF overexpression on the proliferation of bone marrow mesenchymal stem cells in Sprague-Dawely rats.

    METHODS: Bone marrow mesenchymal stem cells from Sprague-Dawley rats were cultured to the third generation in vitro and were divided into blank control group, negative control group, silent p75NTR group, NGF overexpression group, and silent p75NTR combined with NGF overexpression group. Lentivirus-mediated silencing of P75NTR and overexpression of NGF were transfected into rat bone marrow mesenchymal stem cells to induce P75NTR silencing and NGF overexpression. Inverted fluorescence microscopy was used to observe changes in cell morphology on day 3 after transfection. Flow cytometry was used to detect transfection efficiency and western blot method was applied to detect the expression of P75NTR and NGF. Finally, the cell proliferation activity was detected by MTT method and cell counting kit-8 method.

    RESULTS AND CONCLUSION: Cell growth and distribution were good after co-transfection of lentivirus. The transfection efficiency of the double-gene lentiviral vector exceeded 70%. Compared with the blank control and negative control groups, the expression of P75NTR protein was significantly down-regulated, and the expression of NGF was profoundly up-regulated in the silent p75NTR combined with NGF overexpression group. Compared with the blank control and negative control groups, cell proliferation was significantly increased in the other three groups (P < 0.05), and the fastest proliferation was observed in the silent p75NTR combined with NGF overexpression group. To conclude, silencing P75NTR combined with NGF overexpression co-transfection can promote the proliferation of bone marrow mesenchymal stem cells from Sprague-Dawley rats.

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    Expression of autoimmune regulator during differentiation of mouse embryonic stem cells into thymic epithelial progenitor cells 
    Ma Jingyi, Yang Wenjiang, Li Yuandi, Huang Youjiao, Gao Jie, Li Hong, Hu Rong, Su Min
    2020, 24 (25):  3994-3999.  doi: 10.3969/j.issn.2095-4344.2111
    Abstract ( 377 )   PDF (790KB) ( 55 )   Save

    BACKGROUND: Autoimmune diseases are a class of diseases that cause a strong immune response to the continuous lack of self-tissue-specific antigens in the thymus. Hypothyroidism and unstable expression of tissue-specific antigens in the thymus can limit the therapeutic effect. The thymus is mainly composed of thymic epithelial cells, but the limited number of mature thymic epithelial cells and thymic epithelial progenitor cells in the thymus has greatly limited related research.

    OBJECTIVE: To detect the expression of autoimmune regulator (AIRE) when mouse embryonic stem cells were transformed into thymic epithelial progenitor cells.   

    METHODS: A two-step differentiation method was used to induce the differentiation of mouse embryonic stem cells into endoderm and then into thymic epithelial progenitor cells. The cells were collected at 0, 3, and 13 days of induced differentiation. Immunofluorescence, flow cytometry, western blot and real-time PCR were used to detect the expression of cell-associated genes and proteins.

    RESULTS AND CONCLUSION: Positive expression of OCT4 and SSEA1 was detected by immunofluorescence at 0 day of induction. The double positive expression of SOX17 and FoxA2 was measured by immunofluorescence at 3 days of induction. The positive expression of EpCAM, K5 and K8 were analyzed by flow cytometry at 13 days of induction. During the directional differentiation of mouse embryonic stem cells, real-time PCR indicated that the expression of PAX1PAX9FOXN1 and PLET1 showed an increasing trend. The expression of AIRE gene increased significantly at 0, 3, and 13 days of induction. At the same time, the expression of INS2 gene and GAD67 gene also increased. Western blot assay showed that the expression of AIRE protein gradually decreased at 0, 3, and 13 days of induction; however, insulin protein and GAD67 protein were not detected. Overall findings indicate that mouse embryonic stem cells can successfully differentiate into thymic epithelial progenitor cells with highly expressed AIRE gene, which promotes the expression of INS2 and GAD67 genes, and provides an evaluation basis for cell transplantation in the treatment of autoimmune diseases. 

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    Transplantation of bone marrow mesenchymal stem cells for denervated muscular atrophy  
    Yang Ying, Yan Nan, Tian Wei, Han Cao, Zhang Xiaoyan, Zheng Xin, Liu Shidan, Zhang Shuo, Wang Zhengdong
    2020, 24 (25):  4000-4005.  doi: 10.3969/j.issn.2095-4344.2094
    Abstract ( 466 )   PDF (779KB) ( 77 )   Save

    BACKGROUND: Microscopic surgery or some adjuvant treatments can neither effectively delay nor treat denervated muscle atrophy by repairing damaged nerve cells. Studies have found that bone marrow mesenchymal stem cells have the potential for directional differentiation and repair damaged tissues under certain environmental factors. It is speculated that the cells can play a certain role in repairing denervated atrophic muscles.

    OBJECTIVE: To investigate whether transplantation of bone marrow mesenchymal stem cells can alleviate and retard atrophy of denervated muscles.

    METHODS: Primary bone marrow mesenchymal stem cells were isolated from Sprague-Dawley rats, and passage 3 cells were labeled by BrdU for cell transplantation. Thirty Sprague-Dawley rats were divided into three groups, 10 rats in each group. In the sham operation group, only the main trunk of the sciatic nerve was exposed but not clamped. In the treatment group, the main trunk of the sciatic nerve was clamped and bone marrow mesenchymal stem cell suspension was injected into the gastrocnemius muscle. In the control group, after the sciatic nerve trunk was clamped, the gastrocnemius muscle innervated by the sciatic nerve was injected with DMEM medium of equal volume (without cells and fetal bovine serum). Basso, Beattie and Bresnahan scores were used to evaluate the motor function of the rat’s left hindlimb at 1 and 2 weeks after cell transplantation. Changes in the gastrocnemius muscle fibers were observed by hematoxylin-eosin staining and BrdU immunohistochemical staining at 14 days after cell transplantation.

    RESULTS AND CONCLUSION: The passage 3 bone marrow mesenchymal stem cells were positive for BrdU. The labeled cells could survive in and repair the denervated muscle tissue in the treatment group. Compared with the model group, the denervated muscle fibers of the treatment group recovered from mutual fusion and re-arranged regularly. To conclude, transplantation of bone marrow mesenchymal stem cells can alleviate and retard atrophy of denervated muscles.

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    Changes in the proliferation and angiogenesis of human dental pulp stem cells after treated with prostaglandin E1 combined with basic fibroblast growth factor  

    Xiang Haidong, Cheng Dongmei, Guo Han, Gao Qi
    2020, 24 (25):  4006-4011.  doi: 10.3969/j.issn.2095-4344.2095
    Abstract ( 378 )   PDF (855KB) ( 59 )   Save

    BACKGROUND: Prostaglandin E1 and basic fibroblast growth factor can promote the proliferation of human dental pulp stem cells, but the effects of their combinations on the proliferation of human dental pulp stem cells and angiogenesis are unknown.

    OBJECTIVE: To investigate the effects of prostaglandin E1 combined with basic fibroblast growth factor on the proliferation and angiogenesis of human dental pulp stem cells.

    METHODS: (1) Human dental pulp stem cells were isolated and cultured in vitro. After detection and identification of surface markers, prostaglandin E1 and basic fibroblast growth factor at concentrations of 5, 10, 20, 50 and 100 μg/L were used to treat human dental pulp stem cells in vitro. The untreated cells served as control group. The cell proliferation was detected by cell counting kit-8 assay, and the optimum drug concentration and time of drug action were screened. (2) The in vitro cultured human dental pulp stem cells were divided into four groups: blank control group, prostaglandin E1 group, basic fibroblast growth factor group and combination group. The cell proliferation was detected by cell counting kit-8 assay. Human dental pulp stem cell conditioned medium was extracted. The levels of vascular endothelial growth factor and endostatin in the culture medium were detected by ELISA. The in vitro tubular formation ability of human umbilical vein endothelial cells after culture in conditioned medium was tested by tubule formation experiment.

    RESULTS AND CONCLUSION: The optimum concentration of prostaglandin E1 and basic fibroblast growth factor was 20 μg/L, and the optimum time of action was 2 days. Compared with the blank control group, the relative proliferation rate, level of vascular endothelial growth factor and the angiogenesis ability of human umbilical vein endothelial cell in vitro in the prostaglandin E1, basic fibroblast growth factor and combination groups were significantly increased (P < 0.05), while the level of endostatin was significantly decreased (P < 0.05). All above index levels in the combination group were significantly superior to those in the prostaglandin E1 and basic fibroblast growth factor groups

    (P < 0.05). In summary, prostaglandin E1 combined with basic fibroblast growth factor can promote the proliferation of human dental pulp stem cells and enhance the tubular formation ability of human umbilical vein endothelial cells in vitro

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    In vitro culture of human corneal epithelial stem cells using modified explant culture
    Xu Zhongzhong, Yu Xiaofei, Wang Liya
    2020, 24 (25):  4012-4017.  doi: 10.3969/j.issn.2095-4344.2097
    Abstract ( 353 )   PDF (659KB) ( 93 )   Save

    BACKGROUND: Corneal epithelial stem cells, also known as limbal stem cells, are distributed in the basal layer of limbal epithelium. It is extremely difficult to deal with limbal stem cell deficiency or dysfunction that is caused by severe thermal burn, chemical burn, and chronic inflammation of ocular surface. At present, in vitro culture of corneal epithelial stem cells using tissue engineering technology followed by clinical transplantation is a new and effective therapeutic direction.

    OBJECTIVE: To explore the feasibility of serum-free culture of human corneal epithelial stem cells in vitro using modified explant culture method.

    METHODS: The remaining donor corneal tissues after keratoplasty (less than 8 mm in diameter) were obtained from Henan Eye Bank, and the outer and middle limbus were dissected under surgical microscope. Two culture methods were used to culture human corneal epithelial stem cells. In the conventional explant culture group, the limbal tissues were adhered to the dish with the epithelium being upward, then Keratinocyte-serum free medium (K-SFM) was added into dishes, followed by incubation at 37 °C in a 5% CO2 incubator. In the modified explant culture group, limbal tissues were dissected to immerse in the K-SFM culture medium and incubated at 37 °C in the 5% CO2 incubator for 12 hours. The limbal tissues were then adhered to the dish with the epithelium being downward. The day whenever the cells from the limbal tissues adhered to the dish was marked as the 1st day of culture, and changes in cell morphology and growth were recorded by phase contrast microscopy every day. Immunofluorescent staining was used to detect the expression of K3 and p63 in primary cells on the 5th, 10th and 14th day of the modified explant culture.

    RESULTS AND CONCLUSION: The mean early stage of growth in the modified explant culture group was shorter than that of the conventional explant culture group (P < 0.05), and the mean growth rate of the modified explant culture group was higher than that of the conventional explant culture group (P < 0.05). In the modified explant culture group, cells had a good growth state, and many cells with small size gathered together on the 10th day of culture. On the 14th day, cell clones were formed, and the cells in the clone showed uniform morphology. On the 5th day, K3 highly expressed, while p63 lowly expressed in primary cells. On the 10th day, both of K3 and p63 had an increased expression. On the 14th day, there was no significant increase in the K3 expression, but the expression of p63 increased significantly. In the in vitro serum-free culture condition, the modified explant culture could significantly promote the growth of corneal epithelial stem cells, and expand corneal epithelial stem cells in vitro, which could provide sufficient seed cells for enriching corneal epithelial stem cells and constructing human limbal multilayered epithelial sheets.

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    Intravenous transplantation of olfactory ensheathing cells at different time points for repairing spinal cord injury  

    Chen Yao, Zhang Lijian, Lan Yuanxiang, Wu Yiyang, Xia Hechun
    2020, 24 (25):  4018-4022.  doi: 10.3969/j.issn.2095-4344.2075
    Abstract ( 330 )   PDF (798KB) ( 59 )   Save

    BACKGROUND: Olfactory ensheathing cells promote axonal regeneration, provide nutritional support for the injured host cells and regulate inflammation reaction, which possess potential for spinal cord injury repair.

    OBJECTIVE: To explore the optimal time window for intravenous transplantation of olfactory ensheathing cells in the treatment of spinal cord injury.


    METHODS: Thirty male SPF level rats were used to establish the rat models of spinal cord injury by spinal cord hemisection. Rat models were then randomly divided into five groups: 1-, 3-, 7- and 10-day olfactory ensheathing cell transplantation and PBS groups. Olfactory ensheathing cells were labeled with fluorescent quantum dots. PBS was injected into the rats in the PBS group after spinal cord injury. The injured spinal cord was removed at 1 day after injection. A small animal imager was used to measure the fluorescence transferred to the lesion at different time points. The number of cells transferred to the lesion was measured based on the intensity of fluorescence. The Anti-p75 NGF Receptor antibody was used for immunohistochemistry detection of the injured spinal cord. The study was approved by the Ethics Committee of Animal Laboratory of Ningxia Medical University, No. 2017-073.

    RESULTS AND CONCLUSION: Fluorescent quantum dots could label olfactory ensheathing cells. Results of fluorescence assay and immunohistochemistry indicated that transplanted olfactory ensheathing cells were transferred to the lesion at 1, 3, 7 and 10 days. Most cells were transferred to the lesion at 7 days. Therefore, these results indicate that olfactory ensheathing cells transplanted at different time points after spinal cord injury can be transferred to the lesion, with a number peak at 7 days that is the best time window for cell transplantation.

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    In vitro construction of human amniotic mesenchymal stem cell sheet and its osteogenic differentiation  

    Zou Gang, You Qi, Shen Mengjie, Zhang Jun, Tang Jingfeng, Jin Ying, Liu Yi
    2020, 24 (25):  4023-4027.  doi: 10.3969/j.issn.2095-4344.2104
    Abstract ( 442 )   PDF (703KB) ( 55 )   Save

    BACKGROUND: Human amniotic mesenchymal stem cells (hAMSCs) are a kind of adult stem cells that can be extracted from discarded placenta. Compared with other mesenchymal stem cells, hAMSCs have many advantages such as noninvasive isolation, low immunogenicity and short growth cycle, and thus hAMSCs are an important source of tissue engineering seed cells. Currently, hAMSCs have been applied in the clinical treatment of diabetes.

    OBJECTIVE: To explore a simple method to fabricate hAMSC sheets and to study their potential to differentiate into osteocytes.  

    METHODS: Passage 3 hAMSCs were seeded into culture plates at a high density, and the sheet-forming medium was added to fabricate hAMSC sheet. The structural characteristics of hAMSC sheets were evaluated by histological staining and scanning electron microscopy. The sheet-forming induction medium was added to the passage 3 hAMSCs for 7 continuous days, and then replaced by the osteogenic induction medium for 14 days to construct osteogenic-induced hAMSC sheets. The potential for osteogenic differentiation of hAMSC sheets was assessed by alizarin red staining, immunohistochemical staining, alkaline phosphatase activity, RT-PCR, and western blot assay.

    RESULTS AND CONCLUSION: Hematoxylin-eosin staining results indicated that hAMSC sheets had a multi-layered structure with the cells stacked layer-by-layer and evenly distributed. Under the scanning electron microscope, the hAMSC sheets had a multi-layered structure, and a large amount of extracellular matrices that enveloped the fusiform cells were produced. After 14 days of osteogenic induction, orange-red precipitation was observed by alizarin red staining. Immunohistochemical staining results showed a large amount of type II collagen. Compared with non-induced hAMSC sheet, alkaline phosphatase activity was significantly increased in the osteogenic induced sheet (P < 0.01). The expression levels of type I collagen, osteocalcin, and Runt-related transcript factor 2 mRNA and protein were significantly higher in the osteogenic-induced hAMSC sheet group than the non-induced hAMSC sheet group (P < 0.05). Our findings indicate that this is a simple and economic method to construct the hAMSC sheets in the normal culture medium. Moreover, hAMSC sheets have a good osteogenic differentiation potential that has been confirmed in vitro.  

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    Baicalin protects intestinal mucosal barrier and intervenes acute graft-versus-host disease by regulating autophagy 

    Zhong Ping, Cui Xing
    2020, 24 (25):  4028-4032.  doi: 10.3969/j.issn.2095-4344.2087
    Abstract ( 515 )   PDF (652KB) ( 88 )   Save

    BACKGROUND: Acute graft-versus-host disease is one of the important complications of early death after hematopoietic stem cell transplantation. How to intervene in the course of graft-versus-host disease is a hot topic.

    OBJECTIVE: To explore the mechanism of baicalin regulating autophagy in the treatment of acute intestinal graft-versus-host disease.

    METHODS: Within 4 hours after 60Co irradiation in CB6F1 mice, mononuclear cell suspension (bone marrow + spleen) of Balb/c mice was immediately infused into the tail vein to establish haploid hematopoietic stem cell transplantation model. On the day after the establishment of the model, the rats in the model group were intragastrically given normal saline and the rats in the treatment group were intragastrically given baicalin at a dose of 30 mg/(kg·d) for 14 days. After treatment, clinical evaluation of acute graft-versus-host disease was conducted in mice. Pathological grade of acute graft-versus-host disease of small intestinal mucosa was analyzed. Autophagic vesicles in small intestinal mucosa were observed by transmission electron microscopy. Levels of reactive oxygen species in intestinal epithelial cells were detected by flow cytometry. The expression levels of autophagy related proteins LC3-II, LC3-I and Beclin1 were detected by western blot assay.

    RESULTS AND CONCLUSION: The scores of acute graft-versus-host disease and intestinal mucosa pathology grade in the treatment group were significantly better than those in the model group. Under transmission electron microscope, there were autophagic vesicles in the model group, but the mitochondrial structure was seriously damaged. In the treatment group, there were more autophagic vesicles and the mitochondrial structure was relatively intact. The level of reactive oxygen species in small intestinal epithelial cells in the treatment group was lower than that in the model group (P < 0.01). The expression level of LC3II/I and Beclin1 in the treatment group was significantly higher than that in the model group (P < 0.01). The results showed that baicalin could reduce the level of reactive oxygen species, increase the autophagy level of intestinal mucosal cells, protect intestinal mucosal barrier, and reduce the incidence rate of acute graft-versus-host disease after transplantation.

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    Expression of immune-related genes in peripheral blood leukocytes of postmenopausal osteoporosis patients  

    Chen Tianning, Yang Tieyi, Shao Jin, Kong Dece, Liu Shuyi, Zhou Wenchao, Zhang Yan
    2020, 24 (25):  4033-4038.  doi: 10.3969/j.issn.2095-4344.2090
    Abstract ( 376 )   Save

    BACKGROUND: Bones are currently considered as an immune organ. A variety of immune cells that originate from the bone marrow can interact with the cells of the skeletal system to jointly regulate bone metabolism. Explorations on the pathogenesis of postmenopausal osteoporosis as well as treatment-related molecular targets and signal pathways can help prevention and treatment of the disease.

    OBJECTIVE: To investigate the expression profiles of immune-related genes in peripheral blood leukocytes of postmenopausal osteoporosis patients using RNA-Seq technology.

    METHODS: Forty female patients who had experienced menopause for 0 to 20 years and were hospitalized due to fractures were enrolled. They were divided into normal bone mass group (T > -1) and osteoporosis group (T < -2.5) by scanning with Lunar Prodigy dual-energy X-ray bone densitometer. Then, the total RNA of leukocytes in the peripheral blood samples from five patients of each group was extracted. Differentially expressed genes between two groups were detected by RNA-Seq technology followed by GO enrichment analysis. The immune-related genes were screened and analyzed by KEGG signal pathway. Peripheral blood samples from 20 patients of each group were collected and the results of KEGG PATHWAY bioinformatics analysis were verified by real-time PCR. The implementation of the study plan complied with the relevant ethical requirements of the Pudong New Area Gongli Hospital, Shanghai (approval No. 20170301).

    RESULTS AND CONCLUSION: Compared with the normal bone mass group, 187 genes were significantly changed in the osteoporosis group (fold change > 2), and 131 genes were up-regulated and 56 genes were down-regulated. We identified in total 29 differentially expressed immune-related genes including 25 up-regulated and 4 down-regulated ones. There was significant difference in expression between the osteoporosis and normal bone mass groups for genes, including KIR3DL1, KIR3DL2, KIR2DL4, KLRD1 and HSPA6 (P < 0.05). These differentially expressed genes are potentially important for the natural killer cell-mediated cytotoxicity by the KEGG pathway analysis. KIR3DL1, KIR3DL2, KIR2DL4, KLRD1 and HSPA6 may be closely related to the natural killer cell-mediated cytotoxicity during the occurrence of postmenopausal osteoporosis.

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    Stem cell expansion and hepatic differentiation: measurement of related indicators and detection methods 

    Yang Jiayi, Zhang Guanghao, Zhang Cheng, Li Ke, Huo Xiaolin, Wu Changzhe
    2020, 24 (25):  4039-4045.  doi: 10.3969/j.issn.2095-4344.2082
    Abstract ( 321 )   PDF (767KB) ( 109 )   Save

    BACKGROUND: Stem cells have wide application prospects in tissue engineering, regenerative medicine, cell therapy and drug research. In recent years, the applied research, such as bioartificial liver, requires large-scale and high-quality stem cells by expansion, and final obtains hepatocytes (hepatocyte-like cells) by directional differentiation. Through this way, how to efficiently obtain the differentiated cells, with excellent consistency, powerful function and uniform expression of markers, are the key problems to be solved.

    OBJECTIVE: To review the detection indicators and detection methods related to the process of stem cell expansion and hepatic differentiation, summarize the indicators and methods that have been applied to online detection, discuss the limitations of some indicators and methods applied to online detection, and prospect the indicators and detection technologies expected to be applied to online detection in the future.

    METHODS: PubMed, Web of Science, Elsevier and CNKI databases were retrieved for the articles concerning stem cell expansion and hepatic differentiation published from 1990 to 2019. The literature related to stem cell expansion and hepatic differentiation was collected. The keywords were “stem cells; expansion; hepatic differentiation; monitoring; real-time online” in English and Chinese, respectively. A total of 93 articles were searched, and finally 53 eligible articles were selected and reviewed.

    RESULTS AND CONCLUSION: There are many detection indicators and detection methods for stem cell expansion and hepatic differentiation. Among them, the detection indicators of the expansion process are mainly related to the maintenance of pluripotency, metabolic activity, survival rate, and cancer transformation trend of stem cells. The process of hepatic differentiation varies with cell types, in which, the pluripotent stem cells and the mesodermal lineage adult pluripotent stem cells should differentiate into the endoderm-oriented cells and then the mature hepatocytes (hepatocyte-like cells), while the endodermal lineage adult pluripotent stem cells mainly composed of hepatic stem/progenitor cells can directly differentiate into mature hepatocytes (hepatocyte-like cells). The specific markers, survival rate and metabolic activity of cells in different stages of differentiation are the focus of detection. At present, although the detection methods based on large-scale biochemical detection and analysis equipment have high reliability, they face the problems of poor real-time performance, high cost and difficulties in integration and miniaturization. Future concerns are focused on the screening of key detection indicators, quantification of detection criteria and realization of automatic online detection during stem cell expansion and hepatic differentiation.

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    Endothelial progenitor cells promote vasculogenesis and osteogenesis in the repair of bone defects   

    Feng Yuan, Han Zhiqi, Zhou Nuo
    2020, 24 (25):  4046-4053.  doi: 10.3969/j.issn.2095-4344.2092
    Abstract ( 475 )   PDF (813KB) ( 255 )   Save

    BACKGROUND: Fracture is a common orthopedic disease in clinic. Although most fractures can heal by primary bone healing through surgical treatments, such as rigid internal fixation, malunion is liable to occur in some circumstances, eventually leading to bone defects. Neovascularization at the bone defect site plays a vital role in bone healing. Based on the pro-angiogenic ability of endothelial progenitor cells (EPCs), its capacity for bone regeneration and repair has gradually become the focus of attention.

    OBJECTIVE: To review the use of EPCs transplantation to promote vasculogenesis and osteogenesis in bone defects.

    METHODS: With the key words of “endothelial progenitor cells (EPCs), angiogenesis, vasculogenesis, therapy/treatment, bone defect” in Chinese and English, we performed a computer-based search in CNKI, WanFang and PubMed databases for relevant articles published from 1986 to 2019. Finally, 58 eligible articles were included in result analysis. During the literature retrieval, we followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses.

    RESULTS AND CONCLUSION: Bone defects can promote the activation and homing of EPCs. EPCs can promote vasculogenesis and further trigger bone regeneration. There are still some problems to be solved before the application of EPCs in the treatment of bone defects. More experiments need to be carried out to investigate the exact mechanism of EPCs in vasculogenesis. More clinical trials are warranted, providing data support for future clinical applications and giving better treatment to patients disabled by bone defects.

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    Effect of mechanical stimulation on dental pulp stem cells 

    Li Junqing, Wu Jiayuan
    2020, 24 (25):  4054-4059.  doi: 10.3969/j.issn.2095-4344.2098
    Abstract ( 370 )   Save

    BACKGROUND: Mechanical stimulation plays a necessary regulatory role in developing and repairing many organs and tissues in the human body. Except for biochemical factors, mechanical factors are considered as key regulatory factors that affect the behavior and function of dental pulp stem cells.



    OBJECTIVE: To review the role and effect of cellular mechanical stimulation on the biological behavior of dental pulp stem cells.

    METHODS: PubMed, Embase, Medline and CNKI databases were searched for relevant literatures using the keywords of “human dental pulp stem cells (hDPSCs), mechanical strain, mechanical stretch, mechanical tension, shear stress, cell proliferation, osteogenesis differentiation” in English and Chinese, respectively. Fifty-six articles were finally eligible for review, which were closely related to the proliferation and differentiation of dental pulp stem cells under cellular mechanical stimulation.

    RESULTS AND CONCLUSION: Cellular mechanical stimulation is an important biological factor affecting cell proliferation, differentiation, apoptosis and protein expression. Dental pulp stem cells are mesenchymal stem cells derived from the dental pulp tissue, and their biological behaviors are also affected by cellular mechanical stimulation. Cellular mechanical stimulation is involved in the proliferation, odontogenesis/osteogenesis of dental pulp stem cells. When the dentin is subjected to fluid flow forces, mechanoreceptors are activated to regulate and maintain the integrity of tooth structure. Signal pathways that mediate the biological behavior of dental pulp stem cells include MAPK, Wnt, Akt, BMP-7, and Nrf2/HO-1, which are involved in promoting and inhibiting the proliferation and odontogenesis/osteogenesis of dental pulp stem cells to varying degrees.

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    Insights into immunoregulatory properties of dental-derived mesenchymal stem cells in oral diseases 

    Wang Zhen, Li Xiaolan, Liu Jianguo
    2020, 24 (25):  4060-4067.  doi: 10.3969/j.issn.2095-4344.2100
    Abstract ( 391 )   Save

    BACKGROUND: Mesenchymal stem cells have strong immunoregulatory capabilities. The immunoregulatory characteristics of dental-derived mesenchymal stem cells are closely related to the occurrence and development of oral diseases. However, the specific mechanism of this immunomodulatory effect on the disease is unknown. Therefore, the application of the immunomodulatory properties of dental derived mesenchymal stem cells may play an important role in the treatment and prevention of oral diseases in the future.

    OBJECTIVE: To review the role of the Immunomodulatory properties of dental-derived mesenchymal stem cells in oral diseases from the three following aspects: the mutual regulation mechanism of mesenchymal stem cells derived from different oral tissues and activated immune cells, and the effects of various cytokines and oral pathogens on the immunoregulatory capacity of dental-derived mesenchymal stem cells.

    METHODS: CNKI and PubMed databases were retrieved for relevant literature published from January 2000 to June 2019. The search terms were “tooth-derived mesenchymal stem cells, immunomodulatory properties, immune cells, oral diseases, Porphyromonas gingivalis, periodontitis, dental plaque, dental caries, toll-like receptors” in Chinese and English, respectively. A total of 221 articles were obtained, 64 of which met the standards for result analysis.

    RESULTS AND CONCLUSION: In the past 20 years since the dental-derived mesenchymal stem cells were isolated, researchers have conducted a large number of in vitro experiments on the interaction between several oral tissue-derived mesenchymal stem cells and activated immune cells. The mechanism of action between them has been preliminarily discussed. Different inflammatory mediators and cytokines can differentially activate various immunomodulatory proteins in mesenchymal stem cells, and thus activate their immunomodulatory activities. Therefore, exploration on specific stimuli that activate mesenchymal stem cells and oral pathogenic bacteria to activate dental-derived mesenchymal stem cells may improve the application efficiency of dental-derived mesenchymal stem cells at different stages of the tissue healing process. It will make a breakthrough in the way that the disease is treated.

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    Mesenchymal stem cell-derived exosomes in the treatment of orthopedic diseases: roles and prospects  

    Li Jia, Wang Zhihui, Wu Di, Zhao Yang
    2020, 24 (25):  4068-4072.  doi: 10.3969/j.issn.2095-4344.2074
    Abstract ( 431 )   PDF (634KB) ( 148 )   Save

    BACKGROUND: Mesenchymal stem cell-derived exosomes have many biological functions similar to mesenchymal stem cells. In recent years, a large number of studies have confirmed that stem cell-derived exosomes can play an important role in the repair of injuries such as myocardium, liver, skin and so on, which are expected to become a new method of disease diagnosis and treatment. However, its application in orthopedics is little reported, which deserves further study and exploration.

    OBJECTIVE: To review the latest research results and new advances in the use of mesenchymal stem cell-derived exosomes in bone and soft tissue injury repair.

    METHODS: CNKI and PubMed databases were retrieved with the keywords of “mesenchymal stem cells,


    Exosomes, bone cartilage, arthritis, intervertebral disc, tendon, nerve” in Chinese and English, respectively. Initially, 388 articles were retrieved, and 50 eligible articles were finally included.

    RESULTS AND CONCLUSION: The mesenchymal stem cell-derived exosomes can promote the formation of chondrocytes and osteoblasts under certain conditions, and it can also retard the progression of osteoarthritis. The mesenchymal stem cell-derived exosomes can improve intervertebral disc degeneration through antioxidant and anti-inflammatory effects. The mesenchymal stem cell-derived exosome is a potential biomaterial for promoting fracture healing through a variety of pathways.

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    Role and application of exosomes-mediated miRNAs in the treatment of glioma 

    Zeng Zhaomu, Wen Xichao, Zhang Yuhao, Geng Lianting, Shen Yang, Zheng Kebin
    2020, 24 (25):  4073-4080.  doi: 10.3969/j.issn.2095-4344.2088
    Abstract ( 363 )   PDF (840KB) ( 85 )   Save

    BACKGROUND: Exosomes have become more and more popular in the field of tumor research in recent years. They can carry a large number of bioactive molecules directly to the receptor cells and participate in the


    information exchange between cells. As the highest content and most kinds of non-coding RNA in exosomes, miRNAs play an important role in the proliferation, invasion, drug resistance and immunity of glioma. In addition, miRNAs have potential application value in the auxiliary diagnosis, treatment orientation and prognosis evaluation of glioma.

    OBJECTIVE: To describe the mechanism of exosome miRNAs sorting, the regulatory role in gliomas and its clinical application, to provide literature and theoretical basis for further exploring the relationship between exosome miRNAs and gliomas, and to exert positive significance in the diagnosis and treatment of gliomas.

    METHODS: The first author searched CNKI, WanFang database, PubMed database and EI database. The key words were “glioma, exosomes, miRNAs, sorting mechanism, biomarkers” in Chinese and English. Totally 118 literatures were retrieved. According to the inclusion and exclusion criteria, and literature supplement, totally 52 literatures were selected for summary and induction, mainly regarding the sorting mechanism of exosome miRNAs, the regulatory role in glioma and clinical application.

    RESULTS AND CONCLUSION: At present, the effective treatment of gliomas cannot meet the clinical needs even though a variety of high-intensity combined treatment schemes are adopted in this study. In this case, it is an important supplement for the clinical treatment of gliomas to propose the application of exosomes-mediated miRNAs in gene therapy of gliomas. Exosomes-mediated miRNAs cannot only play a regulatory role in the occurrence and development of glioma, invasion and metastasis, radiochemotherapy resistance, and immune regulation, but also play a potential role as a biomarker in the grading diagnosis, prognosis evaluation, treatment and other aspects of glioma. This will provide a solid theoretical basis for us to further explore the relationship between exosome miRNAs and glioma, and also has a positive clinical significance in the innovative diagnosis and treatment of glioma.

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    Research progress in mesenchymal stem cells for treating spinal cord injury

    Shi Xu, Liu Jingsong, Wan Ran, Wang Yansong
    2020, 24 (25):  4081-4087.  doi: 10.3969/j.issn.2095-4344.2084
    Abstract ( 433 )   PDF (695KB) ( 409 )   Save

    BACKGROUND: Spinal cord injury is one of the diseases with highest disability. Due to the limited regeneration ability of spinal axons, it is difficult to recover and often leads to severe neurological sequelae. Treatment for spinal cord injury has become a hotspot. With the continuous development of biological and molecular biology



    research, mesenchymal stem cells have been found to possess big potential for treating spinal cord injury, and bring hope for the repair of spinal cord injury.

    OBJECTIVE: To review the treatment efficacy, property, application, limitations and prospects of mesenchymal stem cells in the treatment of spinal cord injury.

    METHODS: Databases of PubMed, Web of Science, WanFang and CNKI were searched for the articles concerning mesenchymal stem cells in the treatment of spinal cord injury. The keywords were “spinal cord injury, mesenchymal stem cell” in English and Chinese, respectively. Finally, 85 articles eligible for the inclusion and exclusion criteria were included for result analysis.

    RESULTS AND CONCLUSION: Mesenchymal stem cells repair spinal cord injury through a variety of mechanisms. For example, after in vivo transplantation, mesenchymal stem cells differentiate into neurons to replace damaged neurons. They secrete various nutrients through paracrine to regulate the microenvironment of spinal cord injury. Meanwhile, mesenchymal stem cells produce various extracellular matrixes, and provide support for axon regeneration, thus promoting neuronal axon regeneration. Although basic experiments have shown that mesenchymal stem cells exert satisfactory role in the treatment of spinal cord injury, the clinical outcome of mesenchymal stem cells is unsatisfactory. It is necessary to further explore the mechanism of action of mesenchymal stem cells in spinal cord injury. 

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    Application of stem cells, tissue engineering scaffolds and neurotrophic factors in the treatment of spinal cord injury  

    Ji Hangyu, Gu Jun, Xie Linghan, Wu Xiaotao
    2020, 24 (25):  4088-4093.  doi: 10.3969/j.issn.2095-4344.2085
    Abstract ( 393 )   PDF (674KB) ( 178 )   Save

    BACKGROUND: Stem cells have multi-directional differentiation potential. Tissue engineering scaffolds can provide support for them. Neurotrophic factors can promote the differentiation of stem cells. The combination of the three therapies to promote the functional recovery of spinal cord injury is one of the current research hotspots.

    OBJECTIVE: To review the research progress of stem cells, tissue engineering scaffolds, neurotrophic factors and their combined transplantation in the treatment of spinal cord injury in recent years.

    METHODS: The authors searched PubMed, ScienceDirect, Medline, and CNKI for original articles from January 2000 to October 2019. The key words were “spinal cord injury, mesenchymal stem cells, issue engineering, neurotrophic factor” in English and Chinese, respectively. Totally 712 studies were retrieved. After strict screening, 79 studies that met the requirements were classified and reviewed.



    RESULTS AND CONCLUSION: Stem cell transplantation alone cannot reconstruct the complex structure and stability of the spinal cord. Biological materials or neurotrophic factors alone cannot replace the loss of neurons during spinal cord injury. Therefore, combined transplantation is the research direction of spinal cord injury treatment. However, due to the differences in the location of spinal cord injury, the tissue of injury and the nutritional requirements of its repair, the characteristics of various stem cells, tissue engineering scaffolds and neurotrophic factors are different. How to optimize the combination of the three is still a huge challenge. 

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    Feasibility of stem cell therapy for renal ischemia/reperfusion injury: a systematic review based on animal experiments  

    Shang Zhizhong, Jiang Yanbiao, Yao Lan, Wang Anan, Wang Hongxia, Tian Yuanxin, Liu Dengrui, Ma Bin
    2020, 24 (25):  4094-4100.  doi: 10.3969/j.issn.2095-4344.2078
    Abstract ( 423 )   PDF (673KB) ( 92 )   Save

    BACKGROUND: With the in-depth investigation of stem cells and better understanding of kidney ischemia/reperfusion injury, stem cell therapy for renal ischemia/reperfusion injury in animal experiments have been developed extensively, and have achieved certain advance. Therefore, it is necessary to conduct a systematic evaluation to explore the specific efficacy of stem cell therapy for renal ischemia/reperfusion injury.

    OBJECTIVE: To systematically evaluate the effects of stem cells on the function and structure of the kidney and the immune function of the body and the feasibility of transformation into clinical practice based on the animal experiments.

    METHODS: Databases of PubMed, Web of Science, Embase, CNKI, VIP and WanFang were searched by computer, and the search time was limited before May 2019. The literature was screened independently by two researchers, and the data were extracted. SYRCLE animal experiment bias risk assessment tool was used to evaluate the methodological quality of the study, and the evidence quality was evaluated using CERQual tool.

    RESULTS AND CONCLUSION: Finally, 17 animal experiments were included, but there was great clinical heterogeneity among the studies. Therefore, we performed a qualitative description. Compared with the placebo group, the renal function (serum creatinine and blood urea nitrogen level), immune status and renal tissue injury in the stem cell therapy group were improved. But the evidence quality of the six outcome indexes was “low”, and there was a certain risk of bias in the study. The exact efficacy of stem cells and the need for further clinical research cannot be determined due to the problems in experimental design and quality of evidence. Therefore, prior to the inception of clinical trial, high-quality pre-clinical study is necessary to further evaluate the effect of stem cells on renal ischemia/reperfusion injury and the feasibility of clinical transformation to reduce the risk of clinical transformation.

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