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    08 January 2023, Volume 27 Issue 1 Previous Issue    Next Issue
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    Electroacupuncture combined with bone marrow mesenchymal stem cells in the treatment of chemotherapy-induced premature ovarian insufficiency in rats
    Ma Munan, Xie Jun, Sang Yuchao, Huang Lei, Zhang Guodong, Yang Xiaoli, Fu Songtao
    2023, 27 (1):  1-7.  doi: 10.12307/2022.722
    Abstract ( 913 )   PDF (2096KB) ( 238 )   Save
    BACKGROUND: Bone marrow mesenchymal stem cells have good effects on treating premature ovarian insufficiency. However, there are still problems such as low homing efficiency and poor effects.  
    OBJECTIVE: To observe the effect of electroacupuncture combined with bone marrow mesenchymal stem cells in treatment of chemotherapy-induced premature ovarian insufficiency.
    METHODS:  Eight SD rats were randomly selected as the normal group from 32 SD rats, and others were randomly divided into ovarian insufficiency group, stem cell group, and combined treatment group, with 8 rats in each group. Cyclophosphamide solution was intraperitoneally injected to create premature ovarian insufficiency model. After modeling, the normal group was left untreated, and the ovarian insufficiency group was injected with 1 mL normal saline via tail vein. The stem cell group and the combined treatment group were injected with 2×106 bone marrow mesenchymal stem cell suspension 1 mL through the tail vein. Rats in the combined treatment group were treated with electroacupuncture for 30 minutes per day for 7 day. After the treatment, heart blood and ovarian tissue were taken to observe the curative effects.  
    RESULTS AND CONCLUSION: (1) Compared with the ovarian insufficiency group, the levels of serum estradiol in the stem cell group and the combined treatment group were significantly increased, and the levels of follicle stimulating hormone were significantly reduced. (2) Compared with the ovarian insufficiency group, the number of ovarian oocytes in the stem cell group and the combined treatment group increased significantly. (3) Compared with the stem cell group, the homing level of bone marrow mesenchymal stem cells in the combined treatment group increased significantly (P=0.004 3), and the expression level of CXCR4 protein also increased (P=0.036). (4) Compared with the ovarian insufficiency group, the two groups receiving treatment had fewer apoptotic cells, lower Bax protein expression levels, and higher Bcl-2 protein expression levels in ovary. Compared with the stem cell group, the Bax expression level was significantly reduced (P=0.028 4), and the Bcl-2 expression level was significantly increased (P=0.036 4) in the combined treatment group. (5) The results showed electroacupuncture promoted the homing of bone marrow mesenchymal stem cells and enhanced anti-apoptosis effects of bone marrow mesenchymal stem cells.
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    miR-31 promotes the proliferation and migration of bone marrow mesenchymal stem cells
    Zhang Yujuan, Yuan Yitong, Du Ruochen, Tian Feng, Fu Yuan, Wang Chunfang
    2023, 27 (1):  66-71.  doi: 10.12307/2022.984
    Abstract ( 614 )   PDF (1858KB) ( 69 )   Save
    BACKGROUND: Bone marrow mesenchymal stem cells have been widely used in the clinical treatment of neurodegenerative-related diseases, but their efficacy is reduced by low cell survival and migration rates at the site of injury. 
    OBJECTIVE: To investigate whether miR-31 can enhance the migration and proliferation of bone marrow mesenchymal stem cells. 
    METHODS: Bone marrow mesenchymal stem cells from C57BL/6 mice were cultured and identified, and the cells were divided into control, miR-31 agomir, and miR-31 antagomir groups. Bone marrow mesenchymal stem cells at passage 3 were inoculated in six-well plates (1×105/well). When the cells reached 50%-80% fusion, miR-31 agomir and miR-31 antagomir were added to the six-well plates after dilution with serum-free DMEM/F12. After 24 hours of transfection, the proliferation level of cells was analyzed by CCK-8 assay as well as the migration ability of cells was analyzed by Transwell assay. Protein expression of matrix metalloproteinase 2 and CXC chemokine receptor 4 was detected by western blot assay. 
    RESULTS AND CONCLUSION: (1) miR-31 was successfully transfected with bone marrow mesenchymal stem cells without transfection reagents and emitted red fluorescence. (2) After transfection, the proliferation ability of cells in the miR-31 agomir group was enhanced compared with the control group, which increased proportionally with time (P < 0.05). Compared with the control group, miR-31 promoted the migratory ability of bone marrow mesenchymal stem cells in the miR-31 agomir group (P < 0.05) and also upregulated protein expression of matrix metalloproteinase 2 and CXC chemokine receptor 4 (P < 0.05). (3) The results indicated that miR-31 could improve the proliferation ability of bone marrow mesenchymal stem cells and promote the migration of bone marrow mesenchymal stem cells, which provides a basic study for efficient targeting of mesenchymal stem cell migration to the site of injury. 
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    Adipose-derived stem cells overexpressing growth hormone promote proliferation and migration of fibroblasts
    Gao Yixuan, Wang Lingfeng, Ba Te, Li Fang, Cao Shengjun, Li Junliang, Zhou Biao, Chen Qiang
    2023, 27 (1):  8-14.  doi: 10.12307/2022.781
    Abstract ( 761 )   PDF (3087KB) ( 169 )   Save
    BACKGROUND: Growth hormone plays an important physiological role in immune regulation, cell proliferation, and protein synthesis. It has been proven that growth hormone can promote the healing of acute and chronic wounds.
    OBJECTIVE: To construct adipose-derived stem cell lines overexpressing growth hormone, and to investigate the effect of adipose-derived stem cell lines overexpressing growth hormone on proliferation and migration of fibroblasts and its molecular mechanism.  
    METHODS: (1) Adipose-derived stem cells were isolated and identified in vitro. (2) Growth hormone-overexpressing lentivirus was constructed. Adipose-derived stem cells were divided into growth hormone group, empty group, and control group. The above three groups were transfected with growth hormone-overexpressing lentivirus, empty lentivirus, and no infection. (3) The mRNA and protein expression levels of growth hormone and related genes of ERK1/2 pathway in cells and supernatants of each group were detected by RT-qPCR, western blot assay, and ELISA. (4) The effects of growth hormone group and empty group on the migration and proliferation of fibroblasts were detected by the scratch test, Transwell test, and MTS test. The expression of related genes in fibroblasts after co-culture with adipose-derived stem cell lines overexpressing growth hormone was detected by RT-qPCR. (5) After inhibiting adipose-derived stem cell lines overexpressing growth hormone by ERK inhibitor, the expression of above-mentioned genes in fibroblasts was observed after co-culture with ERK inhibitor. 
    RESULTS AND CONCLUSION: (1) Adipose-derived stem cells were isolated and identified and the adipose-derived stem cell lines overexpressing growth hormone were successfully constructed. (2) The mRNA and protein expression levels of growth hormone in the growth hormone group were significantly higher than those in the empty group and control group (P < 0.01), and growth hormone in the supernatant of the growth hormone group was higher. The expression of ERK1/2 and p-ERK1/2 protein was up-regulated in the growth hormone group. (3) Compared with the empty group, the growth hormone group promoted the migration and proliferation of fibroblasts (P < 0.05). (4) After adipose-derived stem cell lines overexpressing growth hormone were co-cultured with fibroblasts, the expression of matrix metalloproteinase-2 genes in fibroblasts was down-regulated; the expression of type I collagen gene was up-regulated, and the expression of type III collagen gene was not significantly changed. (5) After inhibition of ERK protein in adipose-derived stem cell lines overexpressing growth hormone, the mRNA expression differences of these genes disappeared. (6) The results showed that lentivirus transfection was efficient in constructing adipose-derived stem cell lines overexpressing growth hormone, and the cells could secrete growth hormone continuously and promote the proliferation and migration of fibroblasts, which might be related to the up-regulation of the intracellular ERK1/2 signaling pathway.  
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    Effects of hydrogel loaded with human umbilical cord mesenchymal stem cells on diabetic wound repair in mice
    Liu Siqi, Wu Mingrui, Qiao Lingran, Xie Liying, Chen Siyu, Han Zhibo, Zuo Lin
    2023, 27 (1):  21-27.  doi: 10.12307/2022.714
    Abstract ( 997 )   PDF (3460KB) ( 231 )   Save
    BACKGROUND: There is a lack of effective treatment methods to promote the healing of the skin wounds of diabetic patients. Human umbilical cord mesenchymal stem cells have been proven to have a variety of therapeutic effects on skin regeneration. Injectable hydrogels have good biocompatibility and adjustability, which can improve the effect of stem cell therapy.  
    OBJECTIVE: Taking the hydrogel loaded with human umbilical cord mesenchymal stem cells as a starting point, to observe its curative effect on diabetic skin wounds in mice, and explore the possible mechanism of action.
    METHODS:  (1) A diabetic model of C57BL/6J mouse was constructed by continuous intraperitoneal injection of streptozotocin solution for 5 days, and the success of the model was evaluated by blood glucose values collected from the tail vein. (2) A mouse back skin injury model was established by using a puncher. The hydrogel group was treated with pure hydrogel. The composite hydrogel group was treated with hydrogel loaded with human umbilical cord mesenchymal stem cells. The control group was treated with the same amount of normal saline. The wound healing was observed on the 7th and 14th days of treatment.  
    RESULTS AND CONCLUSION: (1) The skin wound area of mice in the composite hydrogel group and hydrogel group was significantly smaller than that in the control group at 14 days after gum application (P < 0.05). The skin wound area of mice was significantly smaller in the composite hydrogel group than that in the hydrogel group (P < 0.05). (2) Hematoxylin-eosin staining results illustrated that the new granulation tissue in the composite hydrogel group was significantly more than that in the control group and hydrogel group (P < 0.05). (3) Masson’s staining results clarified that the collagen deposition in the composite hydrogel group was significantly increased compared with the control group and hydrogel group (P < 0.05). (4) The results of immunohistochemical CD31 staining confirmed that the number of new microvessels in the skin trauma was significantly higher in the composite hydrogel group than that in the control group and hydrogel group (P < 0.05). (5) The results of immunohistochemical CD45 staining showed that the area of inflammation in the new skin was significantly reduced in the composite hydrogel group compared with the control group and hydrogel group (P < 0.05). (6) The results of immunofluorescence staining and qRT-PCR showed that compared with the control group and hydrogel group, the amount of M2 macrophages and the level of interleukin 10 in the trauma tissue were significantly higher, and the amount of M1 macrophages and the level of interleukin 6 were significantly lower in the composite hydrogel group (P < 0.05). (7) The above results illustrate that the chlorinated chitosan-β-sodium glycerophosphate composite hydrogel loaded with human umbilical cord mesenchymal stem cells can promote the formation of granulation tissue and microvessels on diabetic wounds, reduce inflammatory response, and promote wound repair.
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    Allogeneic hematopoietic stem cell transplantation in the treatment of 24 patients with severe aplastic anemia
    Fu Chunmei, Zhang Pu, Wang Yang, Li Xiaolin, Xue Yan, Fu Jie, Zhang Cixian, Yang Yujuan, Duan Yaya, Feng Kai
    2023, 27 (1):  15-20.  doi: 10.12307/2022.805
    Abstract ( 1059 )   PDF (1157KB) ( 148 )   Save
    BACKGROUND: Severe aplastic anemia has severe illness and high mortality, which requires rapid recovery of hematopoietic function. At present, hematopoietic stem cell transplantation is the first-line treatment, human leucocyte antigen-matched sibling donor hematopoietic stem cell transplantation is the first choice, and haploidentical hematopoietic stem cell transplantation has also achieved good results as an alternative treatment.
    OBJECTIVE: To investigate the efficacy of allogeneic hematopoietic stem cell transplantation (including matched sibling donor hematopoietic stem cell transplantation and haploidentical hematopoietic stem cell transplantation) in the treatment of severe aplastic anemia. 
    METHODS: The clinical data of 24 patients with severe aplastic anemia diagnosed from April 2015 to July 2021 undergoing allogeneic hematopoietic stem cell transplantation in Xuzhou Center Hospital were retrospectively analyzed. Among them, 8 patients received matched sibling donor hematopoietic stem cell transplantation and 16 patients received haploidentical hematopoietic stem cell transplantation. The pretreatment regimen of 24 patients with severe aplastic anemia was fludarabine, cyclophosphamide and anti-lymphocytic globulin. The prevention of graft versus host disease was cyclosporine combined with short-range methotrexate in matched sibling donor hematopoietic stem cell transplantation, and in haploid matched hematopoietic stem cell transplantation on the basis of this addition of mycophenolate mofetil. 
    RESULTS AND CONCLUSION: (1) Among the 24 patients, 2 severe aplastic anemia patients died of severe infection during pretreatment, and the other 22 patients reached hematopoietic reconstitution. The median time of neutrophil implantation was 12.5 (10-18) days, and the median time of platelet implantation was 14.5 (10-26) days. (2) Totally 22 patients with successful implantation developed acute graft versus host disease in 8 patients (36%), grade III/IV acute graft versus host disease in 2 patients, chronic graft versus host disease in 4 patients (18%), and grade III/IV chronic graft versus host disease in 1 patient. (3) Totally 18 patients survived and 6 patients died. The 5-year estimated overall survival rate was 74%. (4) These results indicate that allogeneic hematopoietic stem cell transplantation is an effective treatment for severe aplastic anemia. Human leucocyte antigen-matched sibling donor is the first choice. When human leucocyte antigen-matched sibling donor is not available, related human leucocyte antigen-haplo identical donor will be an alternative method.
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    Expression of autocrine macrophage migration inhibitory factor and its receptors of human embryonic stem cells
    Wei Yanzhao, Zheng Xiaohan, Gao Shijun, Huang Ting, Wei Xufang, Chen Xinxu, Zhao Zhenqiang
    2023, 27 (1):  34-41.  doi: 10.12307/2022.985
    Abstract ( 582 )   PDF (1599KB) ( 211 )   Save
    BACKGROUND: Embryonic stem cells have a great potential in helping to understand cell development, regenerative medicine, tissue engineering, and cell therapy due to their self-renewal and multidirectional differentiation characteristics. To have a deeper understanding and effective use of human embryonic stem cells, it is necessary to explore and discover the potential molecules that affect the proliferation and survival of human embryonic stem cells. Macrophage migration inhibitory factor is expressed in a variety of human cells. At first, it was thought to be mainly involved in inflammation, but it was later found to play an important role in cell proliferation, differentiation, angiogenesis, and tumorigenesis. However, whether human embryonic stem cells express this important factor and their functions in human embryonic stem cells remain unclear.
    OBJECTIVE: To determine whether human embryonic stem cells express macrophage migration inhibitory factor and its related receptors, determine which receptor interacts with macrophage migration inhibitory factor, and initially explore the effect of macrophage migration inhibitory factor on the proliferation and survival of human embryonic stem cells.
    METHODS: Human embryonic stem cells were cultured. The level of macrophage migration inhibitory factor in the cell culture medium was detected by enzyme-linked immunosorbent assay. The distribution of macrophage migration inhibitory factor in the cell was observed by immunofluorescence confocal microscope. Cell immunofluorescence and western blot assay were utilized to detect the expression of embryonic stem cell related factors. Immunofluorescence confocal microscopy and immunoprecipitation were applied to detect the binding of macrophage migration inhibitory factor and its receptor. Group intervention: Human embryonic stem cells were intervened with ISO-1 (0, 12, 24, 48, 96, 192 μmol/L) for 24 hours to determine the best inhibitory concentration. Different mass concentrations of macrophage migration inhibitory factor (30, 100, 300 μg/L) were incubated with the optimal inhibitory concentration of ISO-1 for 24 hours. CCK-8 assay was used to detect cell proliferation activity. TUNEL staining was used to detect cell apoptosis level. 
    RESULTS AND CONCLUSION: (1) Macrophage migration inhibitory factor was expressed in the cytoplasm, membrane and culture medium of human embryonic stem cells. (2) Human embryonic stem cells expressed macrophage migration inhibitory factor, mainly expressing its receptors CXCR2 and CXCR7. (3) Macrophage migration inhibitory factor mainly bound to the receptor CXCR7. (4) The effect of macrophage migration inhibitory factor inhibitor ISO-1 on cell proliferation and survival: Compared with the blank group, as the ISO-1 concentration increased, the cell gap increased significantly and the cell viability gradually decreased (P < 0.0001). TUNEL assay showed that cell apoptosis rate was significantly increased (P < 0.000 1). (5) After adding different mass concentrations of migration inhibitory factor (30, 100, 300 μg/L), it could weaken ISO-1 (192 μmol/L) induced negative effects on cells; cell viability was significantly increased (P < 0.05); and apoptosis rate was significantly reduced (P < 0.01). (6) The results have shown that human embryonic stem cells express and secrete macrophage migration inhibitory factor, which is an important factor and can be detected in the cytoplasm, cell membrane, and outside the cell. Human embryonic stem cells mainly express the receptors CXCR2 and CXCR7 of macrophage migration inhibitors, instead of the classic receptor CD74. The protein receptor that interacts with macrophage migration inhibitory factor on human embryonic stem cells is CXCR7. No evidence of interaction with CXCR2 has been found, and its role needs further study. In addition, studies have found that macrophage migration inhibitory factors play an important role in maintaining the proliferation and survival of human embryonic stem cells.
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    Effects of conditioned media of different sources on the proliferation of human dental pulp stem cells
    Yang Yan, Wang Jingxian, Zhang Ronghong, Li Chen, Fan Anran, Cui Dongbing, Wu Shumei
    2023, 27 (1):  49-53.  doi: 10.12307/2022.983
    Abstract ( 598 )   PDF (3122KB) ( 144 )   Save
    BACKGROUND: Using conditioned medium and human pulp stem cells, we will initially explore methods to rapidly proliferate human dental pulp stem cells to provide a research basis for future cell treatment and expansion of high-quality seed cells.  
    OBJECTIVE: To preliminarily explore the effect of conditioned medium from different sources on the proliferation of human dental pulp stem cells.   
    METHODS: Human dental pulp stem cells were isolated in vitro and identified by flow cytometry. Fetal bovine serum ultra-high-speed cryogenic centrifugal products, urine ultra-high-speed cryogenic centrifugal products of fracture patients, in vitro culture supernatants of bone marrow-derived dendritic cells, human skin fibroblast cultures and low-glucose DMEM medium were configured into conditioned medium. After co-culture with human pulp stem cell cells, images of cell growth in each group were taken continuously for 72 hours using a cell label-free culture observation device (BioStation-T). The cells were dynamically monitored using a real-time label-free cell analyzer for 150 hours. Differences in normalized cell index values were compared between each group of cells.
    RESULTS AND CONCLUSION: (1) Human dental pulp stem cells are typical of mesenchymal stem cells. Expression of the mesenchymal stem cell surface markers CD90 and CD105 was found, but CD34 and CD45 expression was not observed. (2) Cell label-free culture observation device when dynamically monitoring found that the absorption time in the group was significantly earlier than in other experimental and blank control groups. (3) When detected on a real-time label-free cell analyzer, compared with the blank control group, the normalized cell index values of the fetal bovine serum ultra-high-speed cryogenic centrifugal group, the bone marrow-derived dendritic cell in vitro culture supernatant group, and the human skin fibroblast culture supernatant group were significantly increased (P < 0.001). The normalized cell index value of fracture patients of the urine ultra-high-speed cryogenic centrifugal group was significantly decreased (P < 0.001). (4) The results show that the conditioned medium configured by ultra-high-speed centrifugation, in vitro culture supernatant of bone marrow-derived dendritic cells, and human skin fibroblasts can promote the proliferation of human dental pulp stem cells. Among them, the conditioned medium configured by the fetal bovine serum ultra-high-speed cryogenic centrifugal products also had some protective effects on the cells. 
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    Human periodontal ligament stem cells-derived exosomes interfere with the proliferation and differentiation of MC3T3-E1 cells
    Lan Qian, Gu Yangcong, Xiao Xin, Bi Xueting, Li Na
    2023, 27 (1):  54-58.  doi: 10.12307/2022.998
    Abstract ( 887 )   PDF (1755KB) ( 102 )   Save
    BACKGROUND: Human periodontal ligament stem cells had a strong osteogenic ability, but the effect of human periodontal ligament stem cells-derived exosomes on proliferation and osteogenic differentiation of MC3T3-E1 is not clear. 
    OBJECTIVE: To explore the effect of human periodontal ligament stem cells-derived exosomes on the proliferation and differentiation of MC3T3-E1 cells.
    METHODS: Human periodontal ligament stem cells were isolated and cultured by enzyme digestion. Human periodontal ligament stem cells-derived exosomes were extracted by ultracentrifugation, and identified by transmission electron microscopy, nanoparticle tracking analysis and western blot assay. Effect of different mass concentrations of human periodontal ligament stem cells-derived exosomes on proliferation of MC3T3-E1 cells was detected by CCK-8 assay. The effect of 100 mg/L human periodontal ligament stem cells-derived exosomes on osteogenic mineralization of MC3T3-E1 cells was observed by alizarin red staining. Western blot assay was used to detect the phosphorylation levels of MEK and ERK in MC3T3-E1 cells before and after the intervention of 100 mg/L human periodontal ligament stem cells-derived exosomes.  
    RESULTS AND CONCLUSION: (1) Transmission electron microscopy showed that exosomes were vesicles formed by lipid bilayer. Nanoparticle tracking analysis showed that exosomes were 50-120 nm in diameter and concentrated at 79.86 nm. Western blot assay showed that the exosomes contained expression levels of CD81, CD63 and TSG101. (2) Compared with the control group, human periodontal ligament stem cells-derived exosomes could promote the proliferation of MC3T3-E1 cells in a dose-dependent manner. (3) Compared with the control group, MC3T3-E1 cells were able to form many calcium nodules in the human periodontal ligament stem cell-derived exosome group. Compared with the control group, protein expression of p-MEK and p-ERK increased in MC3T3-E1 cells of the human periodontal ligament stem cell-derived exosome group. (4) It is indicated that human periodontal ligament stem cells-derived exosomes can promote the proliferation and osteogenic differentiation of MC3T3-E1 cells, which may be associated with the activation of MEK/ERK signaling pathway. 
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    Establishment and identification of a protocol for highly efficient differentiation of hepatocytes from human pluripotent stem cells
    Huang Wenjun, Zhou Yafei, Wang Jie, Li Huan, Zhang Yanmin, Zhou Rui
    2023, 27 (1):  28-33.  doi: 10.12307/2022.964
    Abstract ( 607 )   PDF (2158KB) ( 89 )   Save
    BACKGROUND: Similar to the human embryonic stem cells, human induced pluripotent stem cells possess the ability to differentiate into three germ layers and self-renewal capacity. It is of great clinical significance to generate functional hepatocytes from human induced pluripotent stem cells.
    OBJECTIVE: To establish a protocol for the directed differentiation into hepatocytes from human induced pluripotent stem cells. 
    METHODS: Human induced pluripotent stem cells were characterized by a microscope and immunofluorescence. Pluripotent stem cells were differentiated into definitive endoderm, hepatic endoderm, hepatoblasts, and finally functional hepatocytes via sequential modulation of the signaling pathways using recombinant transcription factors. That was, activin A, fibroblast growth factor 4/bone morphogenetic protein 4, hepatocyte growth factor, and tumor suppressor M were added sequentially on days 0, 5, 10, and 15. The morphological features and molecular markers at different stages were dynamically observed by microscopy, real-time quantitative PCR, and ELISA. 
    RESULTS AND CONCLUSION: (1) The human induced pluripotent stem cells exhibited the typical morphology of pluripotent stem cells and expressed high-levels of the induced pluripotent stem cells-specific markers, SSEA4, SOX2, and OCT4. (2) The human induced pluripotent stem cells were successfully induced sequentially into definitive endoderm cells, hepatoblasts, and hepatocytes. (3) Real-time quantitative PCR showed that with the progression of hepatocyte differentiation, the expression of induced pluripotent stem cells marker (OCT4) was decreased. The expression levels of definitive endoderm (GCS and CXCR4) and hepatic endoderm (HNF4α and HNF1β) markers were increased and then decreased. The expression of hepatocyte markers (CYP34A and ALB) was gradually increased. (4) ELISA results further showed that the hepatocytes after 15 days of induction began to secrete liver-specific proteins (albumin and urea), and their secretory function further increased with the prolongation of time. (5) We conclude that a protocol for differentiation of hepatocytes from human induced pluripotent stem cells was successfully established, which provides an unlimited source of hepatocytes for liver regeneration. 
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    Regulation of peroxisome proliferator-activated receptor gamma coactivator 1 beta on stemness expression in breast cancer stem cells
    Zhao Jufen, Ma Rong, Cao Jia, Yu Chuanyang, Tao Xiang, Wang Jia, Wang Libin
    2023, 27 (1):  59-65.  doi: 10.12307/2023.218
    Abstract ( 620 )   PDF (5723KB) ( 165 )   Save
    BACKGROUND: Previous studies have shown that peroxisome proliferator-activated receptor gamma coactivator 1 beta (PGC-1β) affected the proliferation, migration and apoptosis of breast cancer cells through PI3K/AKT/mTOR signaling pathway. However, whether PGC-1β can affect the stemness of breast cancer stem cells through PI3K/AKT/mTOR signaling pathway and its influencing mechanism has not been elucidated.
    OBJECTIVE: To investigate the effect and regulatory mechanism of PGC-1β on stemness of breast cancer stem cells.
    METHODS:  MCF-7 cells were transfected with PGC-1β empty vector, PGC-1β overexpression vector (Lv-PGC-1β) and interference vector (Sh-PGC-1β), respectively. The transfection effect was observed under fluorescence microscope. The relative expression of PGC-1β mRNA and protein after lentivirus transfection was verified by qRT-PCR and western blot assay. The cells of non-transfection group, PGC-1β empty vector group, PGC-1β overexpression vector group and PGC-1β interference vector group were cultured with stemness medium to foster breast cancer stem cells. The formation process of the spheres was observed and recorded under the microscope. Western blot assay was used to verify the relative expression of stemness proteins (ABCG2, ALDH1 and OCT-4), epithelial-mesenchymal transition proteins (E-cadherin, N-cadherin, Vimentin, Slug and ZEB1) and PI3K/AKT/mTOR pathway related proteins.
    RESULTS AND CONCLUSION: (1) MCF-7 adherent cells were cultured in stemness medium to form dense sphere stem cells with good refractive index and high intermediate density. (2) The expression of stemness protein in breast cancer stem cells was significantly higher than that in adherent cells (P < 0.01). (3) Compared with the non-transfection and PGC-1β empty vector groups, the formation time of breast cancer stem cells was shorter, and the number and diameter of spheres were increased in the PGC-1β overexpression vector group (P < 0.01); however, the number of spheroids and the diameter of spheroids decreased in the PGC-1β interference vector group (P < 0.01). (4) The expression of stemness-related proteins in PGC-1β overexpression group was higher than that in non-transfection group and PGC-1β empty vector group (P < 0.01). Epithelial-mesenchymal transition protein E-Cadherin expression was lower in the PGC-1β overexpression vector group than that in the non-transfection group and PGC-1β empty vector group (P < 0.01). The expression levels of N-Cadherin, Vimentin, Slug and ZEB1 were higher in the PGC-1β overexpression vector group than those in the non-transfection group and the PGC-1β empty vector group (P < 0.01). The expression levels of PI3K/AKT/mTOR-related proteins and their phosphorylation-related proteins were higher in the PGC-1β overexpression vector group than those in the non-transfection group and PGC-1β empty vector group (P < 0.01). The results of the PGC-1β interference vector group were opposite to that of the PGC-1β overexpression vector group. (5) These results suggest that PGC-1β can promote the expression of stemness genes and proteins in breast cancer stem cells by activating the PI3K/AKT/mTOR signaling pathway and affecting epithelial-mesenchymal transition.
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    Bone marrow mesenchymal stem cell transplantation can improve bone metabolism in osteoporotic rats
    Feng Hao, Zhang Bin, Wang Jianping
    2023, 27 (1):  72-75.  doi: 10.12307/2022.989
    Abstract ( 413 )   PDF (1396KB) ( 115 )   Save
    BACKGROUND: Studies have confirmed that bone marrow mesenchymal stem cells can increase the level of osteoprotegerin and promote bone metabolism.  
    OBJECTIVE: To analyze the effects of bone marrow mesenchymal stem cells on bone metabolism in osteoporotic rats.
    METHODS:  Totally 42 healthy SD rats used in the experiment were divided into sham operation group, osteoporosis group, and transplantation group (n=14 per group). Rat osteoporosis model was prepared by ovariectomized method in the osteoporosis and transplantation groups. After successful model establishment, bone marrow mesenchymal stem cells were transplanted through the tail vein. At 28 days after transplantation, the serum levels of osteoprotegerin, alkaline phosphatase, tartrate resistant acid phosphatase, osteocalcin, and insulin-like growth factor 1 were detected by ELISA. Western blot assay was used to detect FoxO1 expression in the bone tissues of rats in each group. The AG-IX biomechanics machine was utilized to detect the maximum and breaking loads of the femur. Hematoxylin-eosin staining was used to observe the bone morphology of rats.  
    RESULTS AND CONCLUSION: (1) The expression levels of osteoprotegerin, alkaline phosphatase, and insulin-like growth factor 1 were lower in the osteoporosis group than those in the sham operation group (P < 0.05). Tartrate resistant acid phosphatase and osteocalcin expression levels were higher in the osteoporosis group than those in the sham operation group (P < 0.05). Expression levels of osteoprotegerin, alkaline phosphatase, and insulin-like growth factor 1 were higher in the transplantation group than those in the osteoporosis group (P < 0.05). Tartrate resistant acid phosphatase and osteocalcin expression levels were lower in the transplantation group than those in the osteoporosis group (P < 0.05). (2) The maximum and breaking loads were lower in the osteoporosis group than those in the sham operation group (P < 0.05). The maximum and breaking loads were higher in the transplantation group than those in the osteoporosis group (P < 0.05). (3) The trabeculae became thicker, arranged orderly, and local space was even in the transplantation group, which was significantly improved compared with the osteoporosis group. (4) The expression level of FoxO1 protein in bone marrow tissue of rats was lower in the osteoporosis group than that in the sham operation group (P < 0.05). The expression level of FoxO1 protein in bone marrow tissue of rats was higher in the transplantation group than that in the osteoporosis group (P < 0.05). (5) It is concluded that bone marrow mesenchymal stem cell transplantation can improve bone metabolism in osteoporotic rats. Its therapeutic mechanism is related to promoting the expression of osteoprotegerin, alkaline phosphatase, and FoxO1.
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    Complications and death causes of peripheral blood stem cell transplantation in the treatment of thalassemia major
    Huang Chuwen, Jiang Hua, Li Minqing
    2023, 27 (1):  42-48.  doi: 10.12307/2022.982
    Abstract ( 712 )   PDF (1191KB) ( 121 )   Save
    BACKGROUND: Allogeneic hematopoietic stem cell transplantation is the only effective method to cure thalassemia major. However, the risk factors influencing the prognosis of transplantation remain unclear. 
    OBJECTIVE: To analyze the distribution of common complications and cause of death after allogeneic hematopoietic stem cell transplantation in children with thalassemia major, and to explore the prognostic factors so as to provide references for improving the survival rate of patients.  
    METHODS: This retrospective cohort study included 257 patients with β-thalassemia major who underwent allogeneic hematopoietic stem cell transplantation at Department of Hematology and Oncology, Guangzhou Women and Children Medical Center between September 2013 and September 2019. There were 172 males and 85 females, with a median age of 6 years at the time of transplantation. The basic clinical data before transplantation and complications after transplantation were compared between the surviving group and dead group using single factor. The overall survival rate was analyzed by the Kaplan-Meier method, and the overall survival rate was compared by the Log-rank test. Multivariate Cox regression was used to analyze factors affecting survival. 
    RESULTS AND CONCLUSION: The median follow-up time was 29 months, and no cases were lost to follow-up. (1) Univariate analysis results showed that there were significant differences in the risk classification between surviving patients and dead patients (P=0.033). Patients with higher risk class had an increased risk of death after transplantation. Multivariate analysis showed that risk classification and severe pneumonia were independent risk factors for overall survival after thalassemia major hematopoietic stem cell transplantation (P < 0.05). (2) Among 20 dead patients, there were 13 patients with severe pneumonia and respiratory failure, 2 patients with grade IV intestinal graft-versus-host disease, 1 patient with intracranial hemorrhage due to thrombocytopenia, 1 patient with thrombocytopenia with acute pulmonary hemorrhage, 1 patient with sepsis with shock, and 1 patient with myasthenia gravis. (3) Totally 17 cases died within 1 year after transplantation, while the rest 3 patients died of severe pneumonia more than 1 year after transplantation. (4) The incidence of bronchiolitis obliterans was significantly higher in patients who died after transplantation than in those who survived (P < 0.000 1). (5) It is concluded that the important factors that affect survival rate in thalassemia major patients after hematopoietic stem cell transplantation are infection and severe graft-versus-host disease. The risk of death increased in patients with bronchiolitis obliterans after transplantation.  
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    Application and progress of small extracellular vesicles in periodontal and pulp regeneration
    Liu Runyuan, Dong Ming, Han Wenqing, Dong Juhong, Niu Weidong
    2023, 27 (1):  83-90.  doi: 10.12307/2022.972
    Abstract ( 832 )   PDF (1871KB) ( 339 )   Save
    BACKGROUND: Small extracellular vesicles are important components of paracrine pathways. In recent years, the application of small extracellular vesicles in oral tissue regeneration attracted wide attention.  
    OBJECTIVE: To review the role and application of small extracellular vesicles in periodontal and pulp tissue regeneration. 
    METHODS: PubMed, Web of Science, CNKI and Wanfang databases were searched for relevant articles published in the past ten years. The retrieval MeSH Terms or key words were “small extracellular vesicles, exosomes, pulp stem cells, periodontal regeneration, bone regeneration, pulp regeneration, regenerative endodontics, revascularization” in Chinese and English, respectively. After removal of poorly related, outdated, and duplicate studies by reading the title and abstract, 71 articles were finally included in result analysis.
    RESULTS AND CONCLUSION: (1) Small extracellular vesicles were secreted by many kinds of cells, participated in intercellular communication and mediated immune response. Small extracellular vesicles have a great application potential in tissue regeneration. (2) Small extracellular vesicles play an important role in periodontal tissue repair and regeneration. Small extracellular vesicles can regulate periodontal inflammation and promote periodontal ligament and surrounding bone tissue regeneration. (3) Small extracellular vesicles improve dental stem cells to regenerate functional pulp-dentin complexes.
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    Neural differentiation and neural biomarker expression of dental pulp stem cells
    Xi Hualei, Xue Bing, Xu Wanqiu, Xu Xiaohang, Yao Lihong, Wang Xiumei
    2023, 27 (1):  91-98.  doi: 10.12307/2022.977
    Abstract ( 777 )   PDF (1477KB) ( 223 )   Save
    BACKGROUND: Dental pulp stem cells have a potential therapeutic value for nervous system diseases due to their wide source, low immunogenicity and excellent ability to differentiate into nervous system cells.  
    OBJECTIVE: To summarize the neurogenic markers of dental pulp stem cells, and provide a research basis for their application in the treatment of clinical nervous system diseases by reviewing the previous studies on the differentiation of dental pulp stem cells into cells of the nervous system.
    METHODS:  Using “dental pulp stem cells, neuro-differentiation, nerve cell markers, nerve” as the Chinese search terms and “dental pulp stem cells, neuro-differentiation, nerve biomarker, nerve” as the English search terms, the computer was used to retrieve articles published on CNKI, Wanfang Data and PubMed databases. According to the inclusion criteria, 85 articles were finally selected for review.  
    RESULTS AND CONCLUSION: (1) Several commonly used neural markers expressed during the differentiation of dental pulp stem cells into neural cells mainly include: nestin, SRY-related HMGbox-containing transcription factor-2, β III tubulin, glial fibrillary acidic protein, microtubule-associated protein 2, S100B, neuron specific enolase, and neuron specific nuclear protein. This article summarizes the characteristics of the above markers, the period of expression and the application of dental pulp stem cells to neural differentiation. (2) Current research shows that to judge whether the differentiation of dental pulp stem cells into neural cells is successful, it is necessary to combine the morphological characteristics and the function of differentiated cells for comprehensive judgment. At the same time, it is difficult to use a single marker to specifically identify a single cell lineage. Therefore, it is necessary to analyze more markers applied to the analysis of one cell type. (3) From the aspects of growth factors, signal pathways, and biological brackets, the method of differentiation of pulp stem cells to neuronal cells is introduced to provide theoretical reference in inducing dental pulp stem cells to neural differentiation.
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    Extracellular vesicles in chronic periodontitis
    Liu Zhuoran, Jiang Ming, Li Yourui
    2023, 27 (1):  99-104.  doi: 10.12307/2022.976
    Abstract ( 659 )   PDF (1262KB) ( 238 )   Save
    BACKGROUND: Extracellular vesicles can control the inflammatory response by participating in immunomodulation of intercellular signaling, while also repairing periodontal tissue and promoting periodontal tissue regeneration. The application of this technology to the preventive diagnosis and tissue regeneration of chronic periodontitis is expected to become a method of cell-free tissue regeneration. 
    OBJECTIVE: To review the synthesis and secretion of extracellular vesicles, biological function, relationship with chronic periodontitis, and recent advances in the diagnosis, prevention and treatment of chronic periodontitis. 
    METHODS: The first author applied the computer to search for relevant studies involving extracellular vesicles in the prevention and treatment of chronic periodontitis in databases such as PubMed, Web of Science and CNKI. The search keywords were “extracellular vesicle, exosome, periodontal disease, immunomodulatory, outermembrane vesicles, bone regeneration” in Chinese and English. The retrieval time was from April 2014 to October 2021. 
    RESULTS AND CONCLUSION: Extracellular vesicles are balloon-like bodies that can be produced by almost all cells, which are widely present in various body fluids, and are rich in proteins, lipids and genetic material on the surface, which affect the biological behavior of target cells by mediating information transfer between cells. On the one hand, the inflammatory response of chronic periodontitis is inseparable from the mediation of extracellular vesicles secreted by bacteria, which can be used as a biomarker to diagnose and evaluate chronic periodontitis; on the other hand, the new chronic periodontitis vaccine made by extracellular vesicles has initially been effective, and the extracellular vesicles containing information molecules can also participate in regulating the immune response and promoting the repair and regeneration of periodontal tissue. Therefore, in the field of tissue damage repair and regeneration of chronic periodontitis, extracellular vesicles are a new and potential cell-free therapy, but their extraction, purification and safety are still challenges to be overcome before clinical translation.  
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    Application of concentrated growth factor and epidermal growth factor in the field of oral and maxillofacial soft and hard tissue injury repair
    Liu Yunling, He Ruya, Nie Minhai, Li Tengyan, Liu Xuqian
    2023, 27 (1):  105-113.  doi: 10.12307/2022.720
    Abstract ( 631 )   PDF (1515KB) ( 295 )   Save
    BACKGROUND: Oral and maxillofacial region is a sensitive part of beauty in appearance, and its damage often involves both soft and hard tissues. Concentrated growth factor and recombinant human epidermal growth factor can promote the repair and regeneration of local soft and hard tissue injury, which has become a new research hotspot in recent years.  
    OBJECTIVE: To review the research progress and application of concentrated growth factor and recombinant human epidermal growth factor in the repair of soft and hard tissue injury in oral and maxillofacial region, and discuss the limitations of current research and the possibility of their combined application in the future.
    METHODS: The English search terms were “CGF, concentrated growth factor, rhEGF, recombinant human epidermal growth factor, tissue regeneration” and the Chinese search terms were “concentrated growth factor, epidermal growth factor, tissue engineering, tissue regeneration, oral and maxillofacial region”. Relevant articles about concentrated growth factor and recombinant human epidermal growth factor were searched in CNKI and PubMed databases. The retrieval time was from 2011 to 2021. Finally, 63 articles were selected.  
    RESULTS AND CONCLUSION: (1) In this paper, the biological characteristics and sources of concentrated growth factor and recombinant human epidermal growth factor were briefly introduced. The research progress and clinical application status of concentrated growth factor and recombinant human epidermal growth factor in promoting the proliferation and differentiation of stem cells related to the regeneration of soft and hard tissues in oral and maxillofacial regions were emphatically summarized. The limitations of current research and possible application directions in the future were discussed. (2) Concentrated growth factor contains a variety of growth factors and CD34+ cells, which can promote the growth, proliferation, migration and differentiation of a variety of tissue cells, especially stem cells, and play an important role in tissue injury repair. (3) Concentrated growth factor is widely used in implant surgery, autologous tooth transplantation, jaw cyst resection, gingival surgery, debridement and suture, which can relieve pain, reduce inflammation, and improve postoperative bone regeneration effect and aesthetic effect. (4) Recombinant human epidermal growth factor has a great development space in soft tissue and nerve regeneration. It has been proven that recombinant human epidermal growth factor can promote a variety of stem cells to differentiate into neuron-like cells, and also induce adipocytes to differentiate into epidermal cells. Most clinical studies suggest that recombinant human epidermal growth factor can promote healing of oral ulcers and reduce scar formation. (5) “Concentrated growth factor + recombinant human epidermal growth factor” combined with adipose-derived stem cells and other stem cells that can be easily obtained have the possibility of directional formation of oral and maxillofacial soft and hard tissue. In the future, it may fill the deep oral and maxillofacial tissue defects caused by trauma, tumor resection, and promote the repair and regeneration of damaged nerves. (6) Trying to use “concentrated growth factor + recombinant human epidermal growth factor” for refractory oral ulcers, periodontal surgery, dental implants, oral and maxillofacial trauma surgery is also a new way to improve oral and maxillofacial function and appearance. Collagen sponge and chitosan membrane may be used as carriers of “concentrated growth factor + recombinant human epidermal growth factor” to facilitate shaping and prolong the action time of the composite.
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    Cellular microenvironment in nerve repair after spinal cord injury
    Zhu Zhenghuan, Zou Hongjun, Song Zhiwen, Liu Jinbo
    2023, 27 (1):  114-120.  doi: 10.12307/2022.971
    Abstract ( 814 )   PDF (7253KB) ( 79 )   Save
    BACKGROUND: Previous studies have shown that a single change in the expression of a gene or the state of a cell in the area of spinal cord injury has no significant effect on functional recovery after spinal cord injury. An increasing number of evidence shows that the regulation of cellular microenvironment after spinal cord injury is a key factor hindering the recovery of neurological function.
    OBJECTIVE: To review the biological characteristics of cellular microenvironment before and after spinal cord injury, including the effect and mechanism of mutual regulation among different kinds of cells and extracellular components on nerve repair after spinal cord injury.
    METHODS: The first author retrieved the databases including PubMed and Web of Science for articles published from January 2000 to December 2021 using the key words of “spinal cord injury, glial cell, neuron, immune cell, neural stem cell, extracellular matrix, cytokine, extracellular vesicle, regeneration”. Finally, 64 articles were selected for analysis. 
    RESULTS AND CONCLUSION: (1) After spinal cord injury, among the cellular components of the cellular microenvironment, the interaction among glial cells, which account for the highest proportion, and the interaction with neurons are particularly critical. (2) Among the extracellular components after spinal cord injury, the hydrogels with good biocompatibility used to imitate natural extracellular matrix can effectively simulate and reconstruct the cellular microenvironment in the injured area and promote axonal elongation. (3) Among the extracellular regulatory factors after spinal cord injury, pro-inflammatory factors such as tumor necrosis factor-α and interleukin-1β aggravate the inflammatory storm of cellular microenvironment. Using receptor inhibitors or blocking related pathways to down-regulate the expression of adverse extracellular regulatory factors is an effective therapeutic method in the cellular microenvironment. At the same time, there are also studies on increasing the expression of anti-inflammatory factors such as interleukin-10 in the microenvironment of the spinal cord and on inhibiting the development of inflammation in the injured area. (4) Recently, extracellular vesicles have also played an important role in the cellular microenvironment as carriers of information. (5) This article reveals multiple sets of mutual regulatory relationships between cellular components and extracellular components in the cellular microenvironment after spinal cord injury, emphasizing that the neuroreparative effects of various components in the cellular microenvironment are not isolated. 
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    Effect of inflammatory reaction mediated by microglia polarization in spinal cord injury
    Shi Xu, Li Ruiyu, Zhang Bing, Chen Qi, Zuo Hua
    2023, 27 (1):  121-129.  doi: 10.12307/2022.731
    Abstract ( 731 )   PDF (1589KB) ( 381 )   Save
    BACKGROUND: Microglia polarization participates in and plays a key role in the inflammatory response after spinal cord injury. Related studies have shown that effectively inducing the polarization of microglia from M1 pro-inflammatory phenotype to M2 anti-inflammatory phenotype can reduce the inflammatory response after spinal cord injury and promote tissue repair and regeneration and the recovery of nerve function.  
    OBJECTIVE: To review the inflammatory response after spinal cord injury, function and polarization of microglia and the effect of microglia polarization on spinal cord injury and its potential regulation strategies.
    METHODS:  Databases of PubMed, Web of Science, and CNKI were searched for the articles with the keywords of “microglia, polarization, spinal cord injury, inflammation” in English and Chinese respectively. Finally, a total of 80 articles were included according to the inclusion and exclusion criteria.  
    RESULTS AND CONCLUSION: (1) Stable and persistent inflammatory response mediated by microglia is very important for the prognosis of spinal cord injury. (2) Under physiological conditions, microglia are in the resting phenotype of M0. After spinal cord injury, microglia are activated and then polarized into M1 pro-inflammatory phenotype, resulting in decreased tissue repair ability and persistent neuroinflammation. (3) During inflammation, regulating the polarization of microglia to M2 phenotype or at least tilting to M2 is beneficial to inhibit oxidative stress, regulate synaptic remodeling, and promote axonal regeneration and angiogenesis. It is an effective control strategy. (4) At present, the main strategies to regulate the phenotypic transition of microglia between M1 and M2 are mesenchymal stem cells, exosomes, clinical drugs, natural products, miRNAs and target molecules. It provides a new idea for the repair of nerve tissue after spinal cord injury. In the future, it is necessary to further study the detailed mechanism of microglia to regulate polarization during spinal cord injury.
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    Progress of non-coding RNAs in stem cell abnormality of idiopathic pulmonary fibrosis
    Huang Bin, Zheng Jinxu, Zhang Jun
    2023, 27 (1):  130-137.  doi: 10.12307/2022.719
    Abstract ( 761 )   PDF (1472KB) ( 181 )   Save
    BACKGROUND: With the development of high-throughput technology, non-coding RNAs have gradually attracted attention and are widely involved in the course of various respiratory diseases. The progression of idiopathic pulmonary fibrosis is accompanied by stem cell abnormality and recent studies have shown that non-coding RNAs are associated with stem cell abnormality, thus affecting the progression of pulmonary fibrosis. Gene therapy that targets non-coding RNAs hints at the possibility of blocking the fibrosis process.  
    OBJECTIVE: To summarize the research progress of non-coding RNAs in stem cell dysfunction and treatment of idiopathic pulmonary fibrosis.
    METHODS:  English search terms included “IPF, stem cells, miRNA, lncRNA, circRNA, treatment” and Chinese search terms contained “idiopathic pulmonary fibrosis, stem cells, miRNA, lncRNA, circRNA, treatment”. Databases including PubMed, Wiley InterScience, CNKI, and Wanfang were used for retrieval, covering articles in the past decade. Screening was performed based on the inclusion and exclusion criteria. Finally, 82 articles were included for analysis.  
    RESULTS AND CONCLUSION: (1) The recent studies on the correlation between non-coding RNAs and the mechanisms of stem cell abnormality in idiopathic pulmonary fibrosis were summarized, revealing that miRNAs, lncRNAs, and circRNAs jointly regulate the abnormal activation and differentiation of stem cells, and miRNAs are often the central link of the mechanisms of lncRNAs and circRNAs. (2) Existing trials have confirmed the safety of transplantation therapy to a certain extent, but in terms of efficacy, the diffusion function of patients has only been slightly improved, but the degree of fibrosis has not been significantly alleviated. Most importantly, the trials were non-randomized and lack of placebo controls, so more placebo-controlled randomized trials are needed. (3) The most important advantage of non-coding RNA-targeted gene therapy is that it has the characteristics of multi-gene regulation, which can intervene stem cell abnormalities from the upstream pathways. Based on the breakthroughs made in vivo and in vitro research, non-coding RNAs have been confirmed to be related to the targets of several drugs for idiopathic pulmonary fibrosis. (4) However, the disadvantages of gene therapy include that it still can only produce short-term effects, and it also faces problems such as effective dose, drug stability, and delivery in the human body. These problems need to be further resolved by future research. (5) In conclusion, although non-coding RNA-targeted therapy is difficult, it can be regarded as a novel way to improve the abnormality of stem cells in idiopathic pulmonary fibrosis, and combining this therapy with stem cell transplantation may achieve better efficacy.
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    Effect of urine-derived stem cells and their exosomes on kidney diseases
    Guo Yujun, Lu Wenjun, Yang Shulong, Li Zhaozhu
    2023, 27 (1):  138-144.  doi: 10.12307/2022.956
    Abstract ( 1135 )   PDF (1938KB) ( 151 )   Save
    BACKGROUND: Urine-derived stem cells, newly found mesenchymal stem cells in urine, have the abilities of self-renewal and multi-differentiation. Because urine-derived stem cells originate from urinary system, and kidneys are the most possible origin, whose diseases are close to where urine-derived stem cells intrinsically reside, urine-derived stem cells and their exosomes may have special effects on kidney diseases compared with other types of mesenchymal stem cells. 
    OBJECTIVE: To review bio-characteristic of urine-derived stem cells and their exosomes and their applications in kidney diseases so as to provide new ideas for the treatment of clinical kidney diseases.
    METHODS: PubMed database was searched using the English key words of “urine-derived stem cell*, urine-derived stromal cell*, urine-derived mesenchymal stem cell*, urine-derived mesenchymal stromal cell*, urine-derived progenitor cell*, kidney diseases, acute kidney injury, diabetic nephropathies, kidney failure, chronic, tissue engineering, organoids”. CNKI database was searched using the Chinese key words of “urine-derived stem cells, acute kidney injury, chronic kidney disease, diabetic nephropathy, tissue engineering, organoids”. The publication date was set from January 2000 to October 2021. Thirty-one articles were involved in the review after manually screening according to the inclusion and exclusion criteria.  
    RESULTS AND CONCLUSION: (1) Urine-derived stem cells are characterized by features that mesenchymal stem cells commonly present. Additionally, urine-derived stem cells serve as an efficacious interference and seed-cells in the treatment of kidney diseases. (2) Urine-derived stem cells and their exosomes have the ability of ameliorating functional and histological injury, inhibiting inflammation, cell apoptosis and oxidative stress of kidneys in animals and cell models of acute kidney injury. In chronic kidney diseases and diabetic nephropathy, urine-derived stem cells and their exosomes can delay deterioration of renal function and histopathology manifestation, inhibit infiltration of inflammatory cells and fibrosis of the tissue and protect podocytes. Furthermore, urine-derived stem cells and exosomes serve as a promising interference in the field of kidney tissue engineering and regenerative medicine. (3) Although these researches are in primary stage, substantial potentials of urine-derived stem cells and their exosomes are sighted, and they are expected to become an efficient stem cell-based therapy for kidney diseases in the future.
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    Biological effects of magnetic field on osteogenesis of mesenchymal stem cells
    Zhang Jinglan, Zhang Binjing, Chen Yifei, Zhang Chenyue, Hu Zhiai, Hu Haikun
    2023, 27 (1):  145-151.  doi: 10.12307/2022.967
    Abstract ( 885 )   PDF (1313KB) ( 152 )   Save
    BACKGROUND: Mesenchymal stem cells, with self-replication and multidirectional differentiation potential, attracted much attention in the field of bone tissue regeneration. As a non-invasive physical stimulation factor, the magnetic field can effectively regulate the biological behaviors of mesenchymal stem cells such as adhesion, proliferation, osteogenic differentiation and mineralization, which means that it has a broad application prospect in bone tissue regeneration medicine. The effect of the magnetic field depends on parameters such as magnetic field strength, frequency and exposure time. Due to the window effect, the appropriate parameter range of magnetic field promoting bone regeneration remains to be clarified.
    OBJECTIVE: To review the effects of different magnetic fields and different magnetic parameters on osteogenic differentiation of mesenchymal stem cells as well as the possible mechanisms, and to summarize the appropriate parameters for promoting proliferation and osteogenic differentiation.
    METHODS: Databases of CNKI and PubMed were searched for relevant articles published from January 2010 to September 2021 using the keywords including “magnetic field, static magnetic field, pulsed electromagnetic field, mesenchymal stem cells, proliferation, osteogenic differentiation, bone regeneration, bone repair” in Chinese and English. A few classic early articles were also included. By reading the titles and abstracts, a preliminary screening was conducted. Repetitive studies, low-quality or irrelevant articles were excluded. Finally, a total of 56 articles were retained and analyzed for this review.
    RESULTS AND CONCLUSION: (1) Moderate static magnetic field, low frequency or low intensity pulsed electromagnetic field, have positive effects on the proliferation and osteogenic differentiation of mesenchymal stem cells. High-frequency pulsed electromagnetic field produces obvious inhibitory effect. (2) The magnetic field modulation effect was positively correlated with the total exposure time, but its effect did not increase with the time of single intermittent exposure. (3) Factors outside the magnetic field, such as stem cell type, differentiation stage, and cell density, also have complex effects on the biological effects of the magnetic field, which should be paid attention to in clinic. (4) Magnetic fields have effects on cellular targets such as plasma membrane, cytoskeleton and ion channel. The possible mechanisms mainly include magnetomechanical interaction, electrodynamic interaction and free radical effect.
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    Potential of mesenchymal stem cell preconditioning strategies in the treatment of severe burn injury
    Lou Hanxiao, Liu Wenjun, Liu Jun, Wang Xin, Zhang Gaofei, Wang Di, Li Jiamei
    2023, 27 (1):  152-159.  doi: 10.12307/2022.965
    Abstract ( 786 )   PDF (1335KB) ( 213 )   Save
    BACKGROUND: Mesenchymal stem cells are ideal candidates in regenerative medicine, and their clinical application is currently limited by reduced cell viability and poor paracrine capacity caused by changes in the transplanted microenvironment. The preconditioning strategy is believed to maximize the survival rate and biological role of mesenchymal stem cells in the transplanted microenvironment, providing new ideas and potential for the treatment of severe burn injuries. 
    OBJECTIVE: To review the potential of mesenchymal stem cell preconditioning strategies in the treatment of severe burn injuries.
    METHODS: With “mesenchymal stem cells, MSCs, preconditioning, pretreatment, burn injury, severe burn injury, burn pathophysiology” as the search terms in Chinese and English, the original articles and reviews collected from January 2000 to January 2022 in CNKI database and PubMed database were searched, and screened and analyzed. Finally, 81 articles were selected for review after excluding researches that were not related to this publication, inconsistent, outdated and repetitive, and those with low credibility and poor logical rigor. 
    RESULTS AND CONCLUSION: (1) The traditional treatment methods after severe burn injury are fluid resuscitation, airway management, infection prevention and control, organ support, early eschar decompression and eschar autograft and allograft transplantation. Clinical treatment still faces great challenges. (2) Mesenchymal stem cells have become a hot spot for treatment because of their low immunogenicity, easy access, and strong tissue repair ability. (3) Once mesenchymal stem cells are applied to burn wounds, they will face the oxidative stress environment caused by ischemia/hypoxia and increased production of reactive oxygen species, resulting in decreased cell survival rate and biological activity. (4) Strategies such as cytokine preconditioning, hypoxia preconditioning, gene modification and drug preconditioning can play a role in treating wound infection, reducing excessive inflammation, relieving hypermetabolic state, regulating immune system, promoting wound healing, and inhibiting therapeutic potential of hypertrophic scars. (5) The application of pretreatment strategies in the clinical treatment of severe burn injuries is limited due to the small number of patients with severe burns and insufficient clinical data to support them. (6) The efficacy and safety of preconditioning strategies in the treatment of severe burn injuries need to be determined through a large number of preclinical studies and clinical cases.
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    Safety and efficacy of mesenchymal stem cells in the treatment of ischemic stroke: a meta-analysis
    Hu Fei, Wang Jie
    2023, 27 (1):  76-82.  doi: 10.12307/2022.981
    Abstract ( 845 )   PDF (1417KB) ( 121 )   Save
    OBJECTIVE: To systematically evaluate the safety and efficacy of mesenchymal stem cells in the treatment of ischemic stroke, and to provide relevant evidence-based medicine evidence. 
    METHODS: Clinical controlled trials of mesenchymal stem cells in the treatment of stroke were searched from Chinese databases (CNKI, Wanfang, and VIP) and English databases (PubMed, The Cochrane Library, and Embase) for articles published until September 30, 2021. The United States National Institutes of Health Stroke Scale score, Barthel index, Fugl-Myer movement assessment score, functional independence measure score, and Modified Rankin Scale score were used as outcome measures. Literature screening, data extraction and research quality assessment were conducted independently by two researchers. The qualities of randomized controlled trials were assessed using Cochrane bias risk assessment tool. Stata 15.0 was used for meta-analysis, sensitivity analysis and forest plot making. 
    RESULTS: A total of 1 127 patients with ischemic stroke were included from 20 randomized controlled trials. The overall quality of the literature was high. Meta-analysis results showed that the scores of National Institutes of Health Stroke Scale, Fugl-Myer movement assessment and functional independence measure score in the mesenchymal stem cell group were better than those in the control group after 3 months of treatment [WMD=-2.12(95%CI:-2.66 to -1.58, Z=7.70, P < 0.001), WMD=14.34(95%CI:12.99-15.68, Z=20.90, P < 0.001), WMD=20.94(95%CI:9.28-22.59, Z=5.88, P < 0.001)]. Barthel index and Modified Rankin Scale score were similar between the two groups [WMD=6.98(95%CI:-2.89-16.85, Z=1.39, P=0.166), WMD=-0.04(95%CI:-0.16 to 0.24, Z=0.44, P=0.663)]. Except for Modified Rankin Scale score, the scores of National Institutes of Health Stroke Scale, Barthel index, Fugl-Myer movement assessment and functional independence measure score were significantly improved at all other time points. 
    CONCLUSION: Mesenchymal stem cell transplantation can improve the neurological deficit, motor function and daily living ability of patients with ischemic stroke.
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