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    08 March 2020, Volume 24 Issue 7 Previous Issue    Next Issue
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    Neuronal differentiation of rat bone marrow mesenchymal stem cells via lentivirus-mediated bone morphogenetic protein 7 transfection
    Zhang Wen, Lei Kun, Gao Lei, Li Kuanxin
    2020, 24 (7):  985-990.  doi: 10.3969/j.issn.2095-4344.1864
    Abstract ( 367 )   PDF (874KB) ( 75 )   Save

    BACKGROUND: Bone marrow mesenchymal stem cells have the potential to differentiate into neuron-like cells, which have been listed as the preferred stem cells for the treatment of spinal cord injury. However, due to their low differentiation efficiency, it is particularly important to find a factor with high induction ability. Based on literature review and our previous studies, it is speculated that bone morphogenetic protein 7 (BMP-7) gene may play a vital role in promoting the differentiation of bone marrow mesenchymal stem cells into neuron-like cells.

    OBJECTIVE: To investigate the differentiation of rat bone marrow mesenchymal stem cells into neurons induced by BMP-7 lentivirus vector transfection.

    METHODS: Bone marrow mesenchymal stem cells of Sprague-Dawley rats were cultured by whole bone marrow adherence method, and then were transfected with LV-GFP when multiplicities of infection were 50, 25, 10, and 1. Green fluorescent protein expression was observed using fluorescence inversion microscope in each group at 3 days after transfection, to confirm the best multiplicity of infection. Passage 3 bone marrow mesenchymal stem cells were divided into blank control group (routine culture), LV-GFP group, and LV-BMP-7-GFP group, followed by transfection at the best multiplicity of infection. After 24, 48, 72, 96, and 120 hours of transfection, MTT assay was used to detect cell survival rate in each group. Immunocytochemical assay was used to detect the expression of nerve cell markers (neurofilament protein 200, synaptophysin-1) after 3 days of transfection.

    RESULTS AND CONCLUSION: (1) After 3 days of LV-GFP transfection, GFP-positive cells were observed under fluorescence microscopy when multiplicities of infection were 10, 25, and 50, whereas no GFP-positive cells were found when the multiplicity of infection was 1. The average fluorescence intensity was the highest when the multiplicity of infection was 10 (P < 0.05), indicating that multiplicity of infection=10 had the best infection effect. (2) Immunocytochemical results showed that the expression of neurofilament-200 and synaptophysin-1 was negative in the blank control group and LV-GFP group, but positive in the LV-BMP-7-GFP group. The cell body and axon in the LV-BMP-7-GFP group were dyed bright brown. In summary, lentivirus-mediated BMP-7 transfection can promote the differentiation of rat bone marrow mesenchymal stem cells into neuron-like cells.

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    Biomechanical analysis of chemical acellular nerve allograft combined with bone marrow mesenchymal stem cell transplantation for repairing sciatic nerve injury
    Wu Zhifeng, Luo Min
    2020, 24 (7):  991-995.  doi: 10.3969/j.issn.2095-4344.2031
    Abstract ( 456 )   PDF (652KB) ( 81 )   Save

    BACKGROUND: It is seldom reported that the effect of chemical acellular nerve allograft combined with bone marrow mesenchymal stem cell transplantation on sciatic nerve injury is evaluated by tensile mechanical properties.

    OBJECTIVE: To determine the effect of chemical acellular nerve allograft combined with bone marrow mesenchymal stem cell transplantation in the treatment of sciatic nerve injury.

    METHODS: Forty-five Sprague-Dawley rats were randomly divided into autologous nerve transplantation group, chemical acellular nerve allograft group, and chemical acellular nerve allograft and bone marrow mesenchymal stem cell transplantation group (n=15 per group). Models of 10-mm sciatic nerve injury were prepared. The injured sciatic nerves were repaired using autologous nerve, chemical acellular nerve allograft and chemical acellular nerve allograft and bone marrow mesenchymal stem cells. At 20 weeks after surgery, electrophysiological measurement and stretching experiments were carried out.

    RESULTS AND CONCLUSION: (1) The wave amplitude and motion conduction velocity were larger in the chemical acellular nerve allograft and bone marrow mesenchymal stem cell transplantation group and autologous nerve transplantation group than in the chemical acellular nerve allograft group (P < 0.05). (2) The tensile elastic limit strain, elastic limit stress, maximum strain and maximum stress were larger in the chemical acellular nerve allograft and bone marrow mesenchymal stem cell transplantation group and autologous nerve transplantation group than in the chemical acellular nerve allograft group (P < 0.05). (3) These results suggest that chemical acellular nerve allograft and bone marrow mesenchymal stem cell transplantation has obvious effect on repairing sciatic nerve injury.

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    Intra-articular injection of optimal concentration of bone marrow mesenchymal stem cells for treating rabbit cartilage defects
    Chen Ganghong, Zeng Chaoming, Chen Ziming, Liao Junxing, Ma Yuanchen, Zheng Qiujian
    2020, 24 (7):  996-1001.  doi: 10.3969/j.issn.2095-4344.2021
    Abstract ( 443 )   PDF (886KB) ( 52 )   Save

    BACKGROUND: Bone marrow mesenchymal stem cells have been extensively applied in animal experiments and clinical studies. The cell concentration, treatment times and results in each study are different, and there is no standard for optimal cell concentration.

    OBJECTIVE: To investigate the optimal concentration of bone mesenchymal stem cells injected into articular cavity in the treatment of rabbit cartilage defects.

    METHODS: Thirty 6-month-old New Zealand white rabbits were selected and randomly divided into control, 1×108, 1×109, 1×1010, and 1×1011/L groups. Cartilage defect models with diameter of 3 mm and depth of 2 mm were established in femoral trochlea in each group. One week after modeling, 1 mL of normal saline was injected into the rabbit’s knee of the control group. The other groups were injected with bone marrow mesenchymal stem cells at corresponding concentrations. After 6 and 12 weeks, gross observation, hematoxylin-eosin staining, Safranin-O-fast green-staining, type I and II collagen staining were performed to assess the cartilage regeneration.

    RESULTS AND CONCLUSION: In the control group, the defect area was obvious with no cartilage regeneration. The 1×108, 1×109, and 1×1010/L groups showed cartilage regeneration. The repairing effect was increased with the cell concentration increasing. The effect of cartilage repair in the 1×1011/L group was similar to that in the 1×1010/L group (P > 0.05). Therefore, 1×1010/L is the optimal concentration for intra-articular injection of bone marrow mesenchymal stem cells for treating cartilage defects, and higher concentration cannot enhance the repairing effect.

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    Knockout of NIPBL gene down-regulates the abilities of proliferation and osteogenic differentiation in mouse bone marrow mesenchymal stem cells
    Lin Ming, Pan Jinyong, Zhang Huirong
    2020, 24 (7):  1002-1008.  doi: 10.3969/j.issn.2095-4344.2029
    Abstract ( 517 )   PDF (1013KB) ( 67 )   Save

    BACKGROUND: Cornelia de Lange syndrome is a genetic disease with multiple developmental defects, of which NIPBL is the main pathogenic gene.

    OBJECTIVE: To investigate the effect of NIPBL gene on the proliferation and osteogenic differentiation of bene marrow mesenchymal stem cells. 

    METHODS: The NIPBL+/- mice were constructed by NIPBL-Loxp and Cre mice and used as experimental group, and the wild-type NIPBL+/+ mice served as control group. Mouse bone marrow mesenchymal stem cells were isolated and cultured in the two groups. Cell proliferation was detected using cell counting kit-8 assay when the cells were passed to the third generation. Osteoblastic differentiation was then compared between two groups after osteogenesis induction.

    RESULTS AND CONCLUSION: The proliferation capacity of bone marrow mesenchymal stem cells in the experimental group was lower than that in the control group (P < 0.05). The activity of alkaline phosphatase in the experimental group was significantly lower than that in the control group on the 7th day of osteogenic induction (P < 0.05). The expression levels of osteogenic genes and proteins (Runx2 and OCN) in the experimental group were lower than those in the control group after osteogenic induction (P < 0.05). On the 21st day of osteogenic induction, results from alizarin red staining indicated there were more red calcium nodules in the control group than the experimental group under inverted microscope. These findings suggest that NIPBL gene knockout can reduce the proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells.

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    Effects of strontium-modified titanium surfaces on adhesion, migration and proliferation of bone marrow mesenchymal stem cells and expression of bone formation-related genes
    Liu Chundong, Shen Xiaoqing, Zhang Yanli, Zhang Xiaogen, Wu Buling
    2020, 24 (7):  1009-1015.  doi: 10.3969/j.issn.2095-4344.2022
    Abstract ( 408 )   PDF (912KB) ( 67 )   Save

    BACKGROUND: Strontium promotes bone formation, and reduces bone resorption. Strontium-modified titanium implant surface has been the focus of research in implant osseointegration under osteoporotic conditions.

    OBJECTIVE: To investigate the cell adhesion, stretch, and migration of advanced strontium-modified titanium surfaces using bone marrow mesenchymal stem cells isolated from rats.

    METHODS: Strontium-modified titanium surfaces were produced by sequential treatments with 5 mol/L NaOH, 100 mmol/L strontium acetate, and heated at 600 or 700 °C for 1 hour. After heat treatment, half the samples were soaked in deionized water at 80 °C for 24 hours, then washed and dried. The pure titanium served as control group, and there were five groups. The whole bone marrow adherence method was used to separate bone marrow mesenchymal stem cells from the rats. The modified titanium sheets were placed in 24-well plates and cultured in cell suspension. Cell adhesion and cell proliferation were assessed using cell counting kit-8 assay. After bone marrow mesenchymal stem cells were with the titanium sheet for 24 hours, the actin was stained to observe cell adhesion and stretch. The migration of bone marrow mesenchymal stem cells on different titanium surfaces was investigated using cell scratch test and fluorescence staining. The expression levels of collagen type І, Runx2, osteoprotegerin, RANKL and osteopontin were detected by qRT-PCR.

    RESULTS AND CONCLUSION: Strontium-modified titanium could promote the stretch and migration of bone marrow mesenchymal stem cells. The number of proliferative cells in the Sr700 group was significantly higher than that in the Sr600 group at 5 days (P < 0.01). On day 14, strontium-modified titanium promoted the expression of collagen type І, Runx2, and osteopontin. In summary, strontium-modified titanium can promote adhesion, spreading, migration and proliferation of rat bone marrow mesenchymal stem cells. Moreover, hydration treatment can enhance the osteogenic activity of rat bone marrow mesenchymal stem cells. 

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    Proliferation and apoptosis of chondrocytes co-cultured with TDP43 lentivirus transfected-human umbilical cord mesenchymal stem cells
    Huang Yongming, Huang Qiming, Liu Yanjie, Wang Jun, Cao Zhenwu, Tian Zhenjiang, Chen Bojian, Mai Xiujun, Feng Enhui
    2020, 24 (7):  1016-1022.  doi: 10.3969/j.issn.2095-4344.2027
    Abstract ( 398 )   PDF (765KB) ( 53 )   Save

    BACKGROUND: TDP43 may be a negative regulator of MAPK signaling pathway under hypoxic-ischemic conditions. However, its effect on JNK and p38 MAPK signaling pathways in osteoarthritis remains unclear.

    OBJECTIVE: To investigate the expression of chondrocyte lesion-related gene RACK1 in wild type TDP43 involved in osteoarthritis, and to analyze its stress effect.

    METHODS: Human umbilical cord mesenchymal stem cells were transfected by TDP43 lentivirus, and the ability to differentiate into chondrocytes in vitro was analyzed. Umbilical cord mesenchymal stem cells transfected by TDP43 lentivirus, empty vector and without transfection were co-cultured with chondrocytes for 12 days. The chondrocyte proliferation was detected at 0, 3, 6, 9 and 12 days of co-culture. The chondrocyte apoptosis rate was detected by flow cytometry at 3 days of co-culture. The expression levels of TDP43, RACK1, p38, JNK, AP-1 and cl-xl in chondrocytes were detected by qRT-PCR at 3 days of co-culture.

    RESULTS AND CONCLUSION: (1) After TDP43 lentivirus transfection, human umbilical cord mesenchymal stem cells could differentiate into chondrocytes. (2) The morphology of chondrocytes co-cultured with TDP43 lentivirus transfected-umbilical cord mesenchymal stem cells showed significant change, and the cells became large with abundant branches. Chondrocytes co-cultured with empty vector transfected- or non-transfected umbilical cord mesenchymal stem cells were spindle-shaped in appearance and showed adherent growth with no morphological changes. (3) After co-cultured with TDP43 lentivirus transfected-umbilical cord mesenchymal stem cells, the apoptosis of chondrocytes was promoted, and the cell proliferation was inhibited (P < 0.05). (4) The expression levels of TDP43, RACK1, p38, JNK, AP-1 and Bcl-xl in the chondrocytes co-cultured with TDP43 lentivirus transfected-umbilical cord mesenchymal stem cells were significantly higher than those in the chondrocytes co-cultured with non-transfected- and empty vector-transfected-umbilical cord mesenchymal stem cells. (5) To conclude, high expression of TDP43 in chondrocytes can activate the expression of RACK1, and further regulate chondrocyte proliferation and apoptosis.

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    Baicalein inhibits the biological behavior of hepatocellular carcinoma stem cells by downregulation of Decoy receptor 3 expression

    Cen Yanhui, Xia Meng, Jia Wei, Luo Weisheng, Lin Jiang, Chen Songlin, Chen Wei, Liu Peng, Li Mingxing, Li Jingyun, Li Manli, Ai Dingding, Jiang Yunxia
    2020, 24 (7):  1023-1029.  doi: 10.3969/j.issn.2095-4344.2017
    Abstract ( 502 )   PDF (859KB) ( 44 )   Save

    BACKGROUND: To date, there is no report on the anti-hepatoma mechanism of Chinese herbal medicine targeting hepatocellular carcinoma stem cells; therefore, relevant research is necessary.

    OBJECTIVE: To observe the effect of baicalein on the expression of Decoy receptor 3 in hepatocellular carcinoma stem cells as well as the biological behavior of hepatocellular carcinoma stem cells after down-regulation of Decoy receptor 3.

    METHODS: Hepatocellular carcinoma stem cells were obtained from hepatocellular carcinoma cell lines (purchased from the Cell Bank, Chinese Academy of Sciences, Shanghai, China), cultured and passaged. The cells were cultured in the low-glucose DMEM containing nothing (control group), 200 (high-dose group), 100 (middle-dose group) or 50 μmol/L (low-dose group) baicalein. After treatment with baicalein, RT-PCR and western blot were used to detect the expression of decoy receptor 3 at mRNA and protein levels. Cell counting kit-8, flow cytometry, and Transwell assay were used to detect the proliferation, cell cycle distribution, apoptosis and migration of hepatocellular carcinoma stem cells.

    RESULTS AND CONCLUSION: Compared with the control group, high-dose baicalein could significantly down-regulated the expression of decoy receptor 3 mRNA and protein in hepatocellular carcinoma stem cells. High-dose baicalein was then confirmed to be the best concentration of action. Compared with the control group, in the high-dose baicalein group, the proliferation ability of hepatocellular carcinoma stem cells decreased significantly, the percentage of S-phase and G2-phase cells increased, while the percentage of G1-phase cells decreased (P < 0.05). Compared with the control group, in the high-dose baicalein group, the apoptotic rate of hepatocellular carcinoma stem cells increased significantly, while the migration ability decreased markedly. To conclude, high-dose baicalein can inhibit a series of biological behaviors of hepatocellular carcinoma stem cells by down-regulating the expression of Decoy receptor 3, which provides an experimental basis for clinical treatment of hepatocellular carcinoma with Decoy receptor 3 as the target and hepatocellular carcinoma stem cells as the object.  

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    Promoting effect of osteopractic total flavone combined with nano-bone materials on proliferation and differentiation of MC3T3-E1 cells 
    Li Jinyu, Yu Xing, Jiang Junjie, Xu Lin, Zhao Xueqian, Sun Qi, Zheng Chenying, Bai Chunxiao, Liu Chuyin, Jia Yusong
    2020, 24 (7):  1030-1036.  doi: 10.3969/j.issn.2095-4344.2034
    Abstract ( 426 )   PDF (1088KB) ( 147 )   Save

    BACKGROUND: Preliminary study has found that osteopractic total flavone can promote osteogenic differentiation of MC3T3-E1 cells on the surface of nano-bone material, but the underlying mechanism needs to be studied in depth.

    OBJECTIVE: To investigate the actin mechanism of osteopractic total flavone combined with nano-bone material on MC3T3-E1 cells.

    METHODS: MC3T3-E1 cells were co-cultured with nano-bone material, and 100 mg/L and 250 mg/L osteopractic total flavone were treated as drug intervention, including 10 μg/L transforming growth factor-β as positive control. The samples were divided into eight groups: (1) Normal group; (2) DKK1 group: Wnt pathway inhibitor DKK1 (0.1 mg/L) blocks Wnt/β-catenin signaling pathway; (3) DKK1+transforming growth factor-β group; (4) DKK1+100 mg/L osteopractic total flavone group; (5) DKK1+250 mg/L osteopractic total flavone group; (6) DKK1+ nano-hydroxyapatite/collagen+transforming growth factor-β group; (7) DKK1+nano-hydroxyapatite/collagen+100 mg/L osteopractic total flavone group; (8) DKK1+nano-hydroxyapatite/collagen+250 mg/L osteopractic total flavone group. Cells in each group were harvested after 24 and 48 hours of intervention. Immunofluorescence labeling was used to observe the binding of Wnt and LRP in osteoblasts in the Wnt/β-catenin pathway. The expression of β-catenin, LRP 5, GSK-3β, Cyclin D1, and RUNX2 was detected by real-time polymerase chain reaction and western blot assay.

    RESULTS AND CONCLUSION: (1) Confocal laser scanning microscope showed that obvious brown and yellow staining was shown in the DKK1+transforming growth factor-β group, DKK1+250 mg/L osteopractic total flavone group, DKK1+nano-hydroxyapatite/ collagen+transforming growth factor-β group, and DKK1+nano-hydroxyapatite/collagen+250 mg/L osteopractic total flavone group, indicating that Wnt and LRP combined better than other groups. (2) Real-time polymerase chain reaction and western blot assay results showed that osteopractic total flavone could promote the expression of β-catenin, LRP5 and RUNX2, and downregulated GSK3β expression. These findings confirm that osteopractic total flavone can promote the differentiation and proliferation of osteoblasts by activating the Wnt/β-catenin signaling pathway. Gene activation induced by osteopractic total flavone was dose-dependent.

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    Transplantation of bone marrow mesenchymal stem cells overexpressing glial cell line derived neurotrophic factor gene for spinal cord injury
    Huang Cheng, Liu Yuanbing, Dai Yongping, Wang Liangliang, Cui Yihua, Yang Jiandong
    2020, 24 (7):  1037-1045.  doi: 10.3969/j.issn.2095-4344.2035
    Abstract ( 381 )   PDF (1128KB) ( 127 )   Save

    BACKGROUND: Glial cell line derived neurotrophic factor (GDNF) plays an important role in inducing differentiation of bone marrow mesenchymal stem cells (BMSCs) in vitro and promoting neurological function recovery in rats with spinal cord injury.

    OBJECTIVE: To observe potential molecular mechanisms of differentiation of BMSCs overexpressing GDNF gene and promoting neurological function recovery after spinal cord injury in rats.

    METHODS: (1) BMSCs transfected with recombinant target gene adenovirus were divided into Ad-GDNF-GFP transfection group, Ad-GFP transfection group and non-transfection group. Microtubule-associated protein 2 and neuron-specific enolase expression levels were detected by immunofluorescence in each group. Western blot assay was used to detect the expression of GDNF, Wnt3a and Wnt7a protein in each group. (2) The rat spinal cord injury model was prepared by modified Allen method. The 45 Sprague-Dawley rat models were randomly divided into three groups. GDNF-BMSCs, BMSCs and PBS were transplanted into the site of spinal cord injury. The motor function recovery of rats was evaluated 4 weeks after operation. The morphological changes of spinal cord were observed by hematoxylin-eosin staining. The local neuron-specific enolase, Synapsin I and glial fibrillary acidic protein were analyzed with immunohistochemistry. The expression levels of Bcl-2 and tumor necrosis factor-α protein were detected by western blot assay.

    RESULTS AND CONCLUSION: (1) BMSCs overexpressing GDNF gene could differentiate into neuron-like cells and express neuron-specific enolase and microtubule-associated protein 2 in vitro in the Ad-GDNF-GFP transfection group. The expression of Wnt3a and Wnt7a protein was significantly higher in the Ad-GDNF-GFP transfection group than in the Ad-GFP transfection group and non-transfection group. (2) The Basso, Beattie and Bresnahan score in GDNF-BMSCs group was significantly increased and the stenosis area was significantly reduced at 4 weeks after transplantation. The expression of glial fibrillary acidic protein and tumor necrosis factor-α in GDNF-BMSCs group was significantly lower than that in BMSCs and PBS transplantation groups, but the expression levels of neuron-specific enolase, Synapsin I and Bcl-2 were significantly higher than those in the BMSCs and PBS transplantation groups. (3) Wnt signaling pathway participates in the procession of differentiating into mature neurons derived from BMSCs overexpressing GDNF gene. After transplantation, the effects of BMSCs transplantation on spinal cord injury were improved by decreasing local inflammatory reaction, apoptosis and glial scar formation and promoting axonal regeneration.

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    Elabela promotes differentiation of Wharton’s jelly-derived mesenchymal stem cells into cardiomyocyte-like cells 
    Qin Xinyu, Zhang Yan, Zhang Ningkun, Gao Lianru, Cheng Tao, Wang Ze, Tong Shanshan, Chen Yu
    2020, 24 (7):  1046-1051.  doi: 10.3969/j.issn.2095-4344.2030
    Abstract ( 418 )   PDF (1021KB) ( 125 )   Save

    BACKGROUND: Elabela is a new type of endogenous receptor of APJ discovered in recent years. It is widely distributed in the adult cardiovascular system and has a certain influence on cardiovascular diseases. However, the effect of Elabela on the differentiation of stem cells into cardiomyocytes and the expression of APJ in cardiomyocyte differentiation has not been studied yet.

    OBJECTIVE: To investigate the effect of Elabela on the differentiation of Wharton’s jelly-derived mesenchymal stem cells into cardiomyocytes.

    METHODS: The frozen mesenchymal stem cells were resuscitated. 5-Azacytidine was used to induce Wharton’s jelly-derived mesenchymal stem cells to differentiate into cardiomyocytes when the cell confluence reached 80%-90%. After 24 hours, the medium was replaced by low-glucose medium containing Elabela and 10% fetal bovine serum in the experimental group, and by low-glucose medium containing 10% fetal bovine serum in the control group. At 7, 14, 21, and 28 days after induction, cell morphology was observed. The total RNA and total protein of each group were collected. The myocardial specific markers Nkx2.5, cTnT and Connexin 43 mRNA and protein expression levels were detected by real-time fluorescent quantitative PCR and western blot assay. The expression of APJ in the induced cardiomyocytes was detected by real-time fluorescent quantitative PCR and flow cytometry.

    RESULTS AND CONCLUSION: (1) The expression levels of myocardial specific markers Nkx2.5, cTnT and Connexin 43 mRNA and protein were higher in the experimental group than in the control group in all stages of differentiation, and the expression of APJ was also higher in the experimental group than in the control group. (2) In summary, Elabela plays a certain promoting role in the differentiation of Wharton’s jelly-derived mesenchymal stem cells into oriented cardiomyocytes. Elabela, as another agonist of APJ, can promote the expression of APJ during the induced cell differentiation. 

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    Zuogui Pill has protective effect against oxidative stress injury in osteoblasts
    Qiao Jiutao, Guan Dehong, Wang Dongyan, Liu Aiyun
    2020, 24 (7):  1052-1056.  doi: 10.3969/j.issn.2095-4344.1854
    Abstract ( 496 )   PDF (692KB) ( 161 )   Save

    BACKGROUND: Recent studies have found that oxidative stress plays an important role in osteoporosis. Osteoporosis is closely related to aging, estrogen deficiency, nuclear factor E2 related factor 2, heme oxygenase 1 and reactive oxygen species production.

    OBJECTIVE: To explore the protective mechanism of Zuogui Pill on oxidative stress injury of osteoblasts. 

    METHODS: The study protocol was approved by the Ethics Committee of the Second Affiliated Hospital of Harbin Medical University. Osteoblasts were isolated and cultured from the skull of neonatal Sprague-Dawley rats, and were divided into three groups: control group, model group and Zuogui Pill group. The oxidative stress injury model of osteoblasts was established with 300 μmol/L H2O2 in the model and Zuogui Pill groups. Osteoblasts in the Zuogui Pill group were cultured with Zuogui Pill containing serum, and the control group did not undertake any treatment. Levels of malondialdehyde and superoxide dismutase in osteoblasts were determined. The expression of nuclear factor E2 related factor 2 and heme oxygenase 1 protein in osteoblasts was detected by western blot.

    RESULTS AND CONCLUSION: Compared with the control group, the content of malondialdehyde increased significantly, and the level of superoxide dismutase decreased significantly in the model group. Compared with the model group, the content of malondialdehyde decreased significantly and the level of superoxide dismutase increased significantly in the Zuogui Pill group. Western blot results showed that nuclear factor E2 related factor 2 and heme oxygenase 1 expression in osteoblasts of the model group increased significantly compared with the control group, and the expression of nuclear factor E2 related factor 2 and heme oxygenase 1 in osteoblasts of Zuogui Pill group was significantly higher than that of the model group. To conclude, Zuogui Pill can protect osteoblasts from oxidative stress injury.

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    Regulation of limbal stem cells via Wnt signaling in the treatment of limbal stem cell deficiency
    Han Bo, Yang Zhe, Li Jing, Zhang Mingchang
    2020, 24 (7):  1057-1062.  doi: 10.3969/j.issn.2095-4344.2028
    Abstract ( 423 )   PDF (727KB) ( 71 )   Save

    BACKGROUND: Wnt signaling pathway plays an important role in the regulation of stem cells, but its regulatory effect on limbal stem cells is not well defined.

    OBJECTIVE: To investigate the regulation of limbal stem cells via Wnt signaling pathway and its function in the treatment of limbal stem cell deficiency.

    METHODS: Rat limbal segments were digested with Dispase and trypsin/EDTA and then single limbal stem cells were seeded in 3D-Matrigel. In experimental group LiCl (500 μmol/L) was added to the culture system. Control group received no LiCl. The expression levels of p63α, CK12, CEBPδ and Ki67 in limbal stem cells were detected by qRT-PCR on the 7th day of culture. The expression level of β-catenin in limbal stem cells was detected by immunofluorescence staining. The rat model of limbal stem cell deficiency was made by alkali burn method. Rats in treatment group were treated with Wnt-activated limbal stem cells by subconjunctival injection. Rats in control group were treated with PBS. Rats were checked by slit lamp every day. On the 4th day after treatment, the immunofluorescence staining and hematoxylin-eosin staining were applied to evaluate the repair of limbus.

    RESULTS AND CONCLUSION: (1) The limbal stem cells aggregated in 3D-Matrigel. β-Catenin was negative in the control group. β-Catenin was found in the cytoplasm and nucleus of the limbal stem cells in the experimental group. (2) qRT-PCR results showed there was no significant difference in the levels of p63α, CK12 or CEBPδ between control and experimental groups (P > 0.05). The Ki67 level in the experimental group was significantly higher than that in the control group (P < 0.05). (3) The rat models of limbal stem cell deficiency were established. The degree of corneal opacity in the treatment group was significantly lower than that in the control group (P < 0.05). Hematoxylin-eosin staining results observed that the corneal epithelial cells in the treatment group were neatly arranged, the cell size was uniform, and repair was good. Immunofluorescence staining showed that β-catenin was found in the cytoplasm and nucleus of most corneal epithelial cells in the treatment group. While β-catenin was only weakly positive in the control group, and was invisible in the cytoplasm or nucleus. (4) These results indicate that activation of Wnt signaling pathway in limbal stem cells enhances their proliferation and keeps them in an undifferentiated self-renewal state. Wnt-activated limbal stem cells can promote the regeneration of corneal epithelium and reduce the degree of corneal opacity in the treatment of limbal stem cell deficiency. The regulation of limbal stem cells via Wnt signaling pathway is expected to provide new ideas for the treatment of limbal stem cell deficiency.

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    Immunomodulatory characteristics of human umbilical cord mesenchymal stem cells in vitro
    Liu Mengting, Rao Wei, Han Bing, Xiao Cuihong, Wu Dongcheng
    2020, 24 (7):  1063-1068.  doi: 10.3969/j.issn.2095-4344.1862
    Abstract ( 441 )   PDF (825KB) ( 71 )   Save

    BACKGROUND: Human umbilical cord mesenchymal stem cells (hUC-MSCs) have been drawing a great attention due to their potential therapeutic effect in a variety of diseases, including immune-mediated diseases. Further characterization of the immunomodulatory properties and action pathways of hUC-MSCs is necessary to ensure their safety and effectiveness in clinical application.

    OBJECTIVE: To investigate the immunomodulatory properties of hUC-MSCs.

    METHODS: hUC-MSCs were directly co-cultured with CFSE-labeled peripheral blood mononuclear cells (PBMCs) at the ratio of 1:5, 1:10, and 1:20, or indirectly co-cultured with CFSE-labeled PBMCs at the ratio of 1:5 via the Transwell co-culture system. Phytohemagglutinin- stimulated PBMC proliferation and the percentages of Th1, Th17 and Treg subgroups in the CD4+ T cells were determined by flow cytometry. The levels of tumor necrosis factor α and interferon γ were determined by ELISA.

    RESULTS AND CONCLUSION: After direct co-culture, hUC-MSCs significantly inhibited the phytohemagglutinin-stimulated PBMCs proliferation in a dose-dependent manner, whereas the inhibitory effect disappeared in the Transwell co-culture system. A significant decrease of Th1, Th17 cells and an increase of Treg cells were detected in the PBMCs co-cultured with hUC-MSCs compared to the PBMCs cultured alone. Furthermore, hUC-MSCs co-culture significantly reduced tumor necrosis factor α and interferon γ levels in the PBMCs. These findings indicate that cell-to-cell contact is essential for hUC-MSCs to inhibit the proliferation, differentiation and inflammatory factor secretion of immune cells.

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    Transplantation of human stem cells from the apical papilla for treating dextran sulfate sodium-induced experimental colitis 
    Li Jia, Tang Ying, Zhu Qi, Zhang Yanping, Zhou Peigang, Gu Yongchun
    2020, 24 (7):  1069-1075.  doi: 10.3969/j.issn.2095-4344.2010
    Abstract ( 422 )   PDF (1238KB) ( 67 )   Save

    BACKGROUND: Stem cells from the apical papilla (SCAP) play important roles in the formation and development of dental roots. However, the immune-modulating capacity of SCAP has not been fully elucidated.

    OBJECTIVE: To test the therapeutic effects of transplantation of SCAP on dextran sulfate sodium-induced experimental colitis.

    METHODS: Twenty-four C57/BL6 mice were equally divided into four groups (normal control, positive control, SCAP treatment group, and FasL-knockdown SCAP group), and latter three groups of mice were induced to acute experimental colitis by 3% dextran sulfate sodium in drinking water. At day 3 after modeling, model mice were treated with PBS, human SCAP (2×106 cells), and FasL-knockdown SCAP via intraperitoneal injection, respectively. Inflammation was evaluated by measuring body mass and length of the colon, detecting levels of interleukin 1β, interleukin 6 and tumor necrosis factor α, as well as histological analyses at day 10 after modeling. Levels of Tregs in mesenteric lymph nodes in mice were detected using flow cytometric analysis.

    RESULTS AND CONCLUSION: SCAP transplantation could ameliorate the inflammation in dextran sulfate sodium-induced colitis mice, and body mass loss and symptoms were significantly improved. Pathological score and the levels of three inflammatory cytokines in the colon tissue decreased significantly. Flow cytometric analysis revealed an increased level of Tregs in mesenteric lymph nodes. Knocking down of FasL gene in SCAP abrogated the therapeutic effects of SCAP in ameliorating dextran sulphate sodium-induced colitis. Therefore, Fas-FasL pathway played an important role in the underlying mechanism of the immune-modulating capacity of SCAP.   

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    Electrical stimulation combined with neurotrophin 3 promotes proliferation and differentiation of endogenous neural stem cells after spinal cord injury in rats
    Zhang Peigen, Heng Xiaolai, Xie Di, Wang Jin, Ma Jinglin, Kang Xuewen
    2020, 24 (7):  1076-1082.  doi: 10.3969/j.issn.2095-4344.2019
    Abstract ( 361 )   PDF (982KB) ( 136 )   Save

    BACKGROUND: Due to limited access to exogenous neural stem cells, immune rejection and ethical problems, how to activate endogenous neural stem cells and promote their growth, proliferation and differentiation has become an issue of concern.

    OBJECTIVE: To investigate the effects of electrical stimulation combined with neurotrophin 3 on the proliferation and differentiation of endogenous neural stem cells into neurons after spinal cord injury in rats.

    METHODS: Ninety-six rats were randomly divided into sham operation (spinal cord exposed only), spinal cord injury, electrical stimulation, and electrical stimulation+neurotrophin groups, 24 rats in each group. A rat model of spinal cord injury was established by modified Allen method in the latter three groups. After the model was established, the rats in the four groups were given corresponding treatments. At 7, 14, 21, and 28 days after modeling, the motor function of hind limbs was evaluated by Basso-Beattie-Bresnahan score. The latency of motor evoked potential was examined by electrophysiology. At 28 days after modeling, samples of the spinal cord were taken for hematoxylin-eosin staining to observe the pathological changes and for immunohistochemical staining to observe the the proliferation and differentiation of endogenous neural stem cells. The study was approved by the Ethics Committee of the Second Hospital of Lanzhou University.

    RESULTS AND CONCLUSION: (1) Compared with the sham operation group, the Basso-Beattie-Bresnahan score in the spinal cord injury group was significantly decreased (P < 0.01), and a large number of inflammatory cells infiltrated into the spinal cord tissues with multiple cavities. Compared with the spinal cord injury group, the hind limb function in the electrical stimulation and electrical stimulation+neurotrophin groups began to recover gradually. Basso-Beattie-Bresnahan score in the electrical stimulation+neurotrophin group was significantly higher than that in the electrical stimulation group (P < 0.05). The above pathological changes were significantly improved. (2) No latency of motor evoked potentials in both hind limbs was detected in the spinal cord injury group at 7, 14 days and in the electrical stimulation group at 7 days, respectively. At 21 and 28 days, the latency of motor evoked potential was shorter in the electrical stimulation and electrical stimulation+neurotrophin groups than in the spinal cord injury group (P < 0.05); and the latency of motor evoked potential in the electrical stimulation+neurotrophin group was shorter than that in the electrical stimulation group (P < 0.05). (3) The number of BrdU and Nestin positive cells and the expression of microtubule-associated protein 2 were ranked as follows: electrical stimulation+neurotrophin group > electrical stimulation group > spinal cord injury group. The expression level of glial fibrillary acidic protein was highest in the spinal cord injury group, followed by electrical stimulation group, and lowest in the electrical stimulation+neurotrophin group. These results show that after electrical stimulation plus neurotrophin 3 intervention, endogenous neural stem cells can proliferate and differentiate into neurons. Pathological damage is significantly alleviated and motor function of hind limbs is significantly improved.

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    Fibroblast growth factor receptor 3 regulation and mechanism in callus formation
    Xu Shaoce, Wang Shiyao, Zhou Jianwei, Pan Yixin, Wang Yuliang
    2020, 24 (7):  1083-1088.  doi: 10.3969/j.issn.2095-4344.1873
    Abstract ( 452 )   PDF (1002KB) ( 141 )   Save

    BACKGROUND: In clinical treatment, patients with traumatic nerve injury and fractures show accelerated fracture healing and excessive osteophyte growth, and even heterotopic ossification in the muscle, all of which seriously affect the therapeutic efficacy on such fractures. The specific causes and mechanisms for the acceleration of fracture healing after denervation are currently unclear.

    OBJECTIVE: To investigate the role and expression of fibroblast growth factor receptors 3 (FGFR3) inhibitor in the process of fracture healing.

    METHODS: The study protocol was approved by the Animal Ethics Committee of Second Hospital of Lanzhou University. Sixty female Sprague-Dawley rats were used to make a transverse humeral fracture model of sciatic nerve injury. They were randomly divided into two groups, experimental group and control group. The experimental group received intraperitoneal injection of FGFR3 blocker; the control group received an equal dose of normal saline. The X-ray films were taken at 4, 7, 10, 14 and 21 days after surgery, and tibia specimens for six animals were subsequently taken at each time point, followed by histological observations using hematoxylin-eosin staining and Masson’s trichrome staining. Osteocyte density and trabecular bone density of the rat tibia were calculated; and the fiber rate of the tibia was determined.

    RESULTS AND CONCLUSION: There were no significant differences in the X-ray findings of the tibia between the two groups. The experimental group had better bone repair than the control group, shown by hematoxylin-eosin staining and Masson’s trichrome staining. Osteocyte density, trabecular bone density, and fiber rate of the rat tibia were significantly higher in the experimental group than the control group at 7-14 days after treatment. Inhibition of FGFR3 can accelerate fracture healing and promote the shaping of callus in the case of peripheral nerve denervation. FGFR3 is most active at 7-14 days after fracture.

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    Mechanism underlying mechanical stress regulating fibroblasts-derived exosomes at the osteotomized end following hallux valgus correction

    Xie Fei, Li Yanle, Lin Xinxiao, Hu Haiwei, Sang Zhicheng, Sun Yongsheng, Jiang Kewei, Cheng Ying, Wen Guannan, Wen Jianmin, Sun Weidong
    2020, 24 (7):  1089-1093.  doi: 10.3969/j.issn.2095-4344.1847
    Abstract ( 378 )   PDF (749KB) ( 85 )   Save

    BACKGROUND: Bandage internal fixation (defined as the interphalangeal insertion of “8”-shaped bandage for elastic external fixation) produces a suitable mechanical environment for bone healing after minimally invasive treatment of hallux valgus. Stress stimulation is essential for bone healing after osteotomy, but the mechanism is still unclear.

    OBJECTIVE: To study the regulatory mechanism of mechanical stress on fibroblasts-derived exosomes.

    METHODS: The medial bone tissue of the first metatarsal bone obtained in the surgery for hallux valgus was taken as a specimen. The fibroblasts were passaged in vitro via direct tissue adherent culture. The loading system provided a cell strain simulating external fixation using “8”-shaped bandage for the pressure-loading culture of hallux valgus fibroblasts, and then exosomes were extracted. Size distribution, morphology and markers of exosomes were detected by electron microscopy, nanoparticle tracking analysis and western blot assay. The study protocol was approved by the Ethics Committee of Wangjing Hospital of China Academy of Chinese Medical Sciences with approval No. 2013-03-21 on March 21, 2013.

    RESULTS AND CONCLUSION: Static stretching (15%) could promote the secretion of exosomes from fibroblasts. The expression of CD9 and CD81 was detected in the fibroblasts-derived exosomes of the control group and the experimental group. Range of exosome particle size distribution was consistent in the two groups of exosomes, and 15% static stretching increased the concentration of exosomes. This indicates that 15% static stretching helps fibroblasts secrete growth factors, which in turn contribute to osteoblast osteogenesis.

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    Involvement of GDNF/PI3K/AKT pathway in promoting facial nerve regeneration using electroacupuncture in a rabbit model of facial nerve crush injury
    Fei Jing, Zheng Hongdi, Yu Liya, Li Leiji
    2020, 24 (7):  1094-1100.  doi: 10.3969/j.issn.2095-4344.1848
    Abstract ( 401 )   PDF (904KB) ( 81 )   Save

    BACKGROUND: The mechanism of electroacupuncture on multi-acupoints in the treatment of peripheral facial paralysis is still unknown. Glial cell-derived neurotrophic factor (GDNF) is currently the most effective factor in promoting the survival of motoneurons in vitro, and the PI3K/AKT pathway plays an important role in protecting damaged motoneurons. There is yet no research on GDNF/PI3K/AKT pathway involved in electroacupuncture promoting facial nerve regeneration in rabbits.

    OBJECTIVE: To observe the effect of electroacupuncture on regeneration after peripheral facial nerve crush injury, and to explore the protective mechanism of electroacupuncture on facial motoneurons through the GDNF/PI3K/AKT signaling pathway.

    METHODS: Sixty-six adult healthy New Zealand white rabbits provided by the Animal Experimental Center of Southwest Medical University were randomly divided into a normal group and a model group. The facial nerves on the right side in the model group were subjected to a crush injury. Then the animal models were randomly divided into a model control group and an electroacupuncture group. Animals in the model control group recovered naturally, while those in the electroacupuncture group underwent electroacupuncture at Yifeng, Jiache, Sibai, Dicang, Yangbai, and Quanliao acupoints daily for 30 minutes. The improvement of facial paralysis symptoms in experimental animals were observed and scored. Tissue samples were directly taken form the normal group, and pons tissues with facial neurons were taken in the model group at 1, 4, 7, 14, and 28 days postoperatively. The morphologies of facial motoneurons and Nissl bodies were observed by hematoxylin-eosin staining and Nissl staining, respectively. Immunohistochemical techniques and western blot assay were used to detect the protein expression of GDNF, PI3K, AKT, and p-AKT in the facial motoneurons. The study protocol was approved by the Animal Ethics Committee of Southwest Medical University with approval No. 20170120001.

    RESULTS AND CONCLUSION: The symptoms of facial paralysis were that the animal’s mouth was drooped at the affected side, with lodging tentacles and the movement being weakened, and the eyelids that could not be lifted, which recovered faster and more completely in the electroacupuncture group than the model control group. The morphological changes of facial neurons and changes of Nissl bodies in the electroacupuncture group were lighter than those in the model control group. At each time point postoperatively, the stronger GDNF immune response could be seen in the electroacupuncture group, and the number of GDNF-positive cells was higher than that of the model control group except 1 day postoperatively (P < 0.001). The expressions of GDNF, PI3K, p-AKT proteins in the facial motoneurons were significantly increased in the electroacupuncture group compared with the model control group (P < 0.05; P < 0.01; P < 0.001). To conclude, electroacupuncture can effectively treat the peripheral facial paralysis caused by the crushed injury of facial nerve and promote the recovery of facial neurons. The up-regulation of GDNF expression in the facial motoneurons and the activation of PI3K/AKT signaling pathway may be the underlying protective mechanism of electroacupuncture.

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    Three-dimensional hanging-drop culture of mesenchymal stem cells in the treatment of tissue injury 
    Deng Junhao, Li Miao, Zhang Licheng, Tang Peifu
    2020, 24 (7):  1101-1106.  doi: 10.3969/j.issn.2095-4344.1849
    Abstract ( 475 )   PDF (693KB) ( 67 )   Save

    BACKGROUND: In recent years, mesenchymal stem cells (MSCs) have been widely used in varieties of tissue repairs due to its easy accessibility, exceptional ability to proliferate, remarkable potential to multi-differentiate, and considerable effects on immunoregulation. However, cell pluripotency and secretory function are often severely impaired when the cells are cultured using the traditional two-dimensional method. Nevertheless, three-dimensionally cultured mesenchymal stem cells cannot only derive the advantages of mesenchymal stem cells per se, but maintain and potentiate cell capacity of proliferation, differentiation and secretion, which therefore enhance the ability to repair various tissue injuries.

    OBJECTIVE: To review the recent studies of three-dimensional cultured mesenchymal stem cells in the treatment of multiple tissue injuries via various aspects including its biological characteristics, underlying mechanisms of tissue repair, culture methods as well as the application in various diseases, in order to elucidate the possibility of its future application and provide theoretical support for the clinical application of three-dimensional mesenchymal stem cells in the future.

    METHODS: We retrieved the main databases including PubMed, CNKI, and WanFang for relevant literature published in recent 10 years. The keywords were “mesenchymal stem cells, three-dimensional culture, hanging-drop culture, tissue repair” both in Chinese and English. The type of the article was not limited. Finally, 51 articles were included for result analysis.

    RESULTS AND CONCLUSION: It has been widely demonstrated that compared with the two-dimensional cultured cells, three-dimensional cultured mesenchymal stem cells show stronger effects on cell proliferation, differentiation, paracrine secretion, and immunoregulation. With the rapid development of three-dimensional sphenoid culture system and stem cell transplantation, three-dimensional cultured mesenchymal stem cells will show its great potential in the treatment of multiple tissue injuries.

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    Research progress in osteogenic differentiation of adipose-derived stem cells induced by bioscaffold materials
    Zhang Shengmin, Liu Chao
    2020, 24 (7):  1107-1116.  doi: 10.3969/j.issn.2095-4344.2026
    Abstract ( 519 )   PDF (1009KB) ( 196 )   Save

    BACKGROUND: Adipose-derived stem cells are easy to access and have strong proliferative capacity, which are considered as ideal seed cells for bone defect repair. The bone tissue engineering research progress reveals that bioscaffold material modification can directly regulate the osteogenic differentiation of stem cells.

    OBJECTIVE: To review various biological scaffold materials that can regulate the osteogenic differentiation of adipose-derived stem cells.

    METHODS: The first author searched the articles in CNKI, WanFang, VIP, PubMed, Embase and Web of Science databases published from January 2016 to May 2019. The search terms were “adipose derived stem cells, scaffold, osteogenic, metal, Ti” in Chinese and English, respectively. Finally 62 eligible articles were selected.

    RESULTS AND CONCLUSION: Scaffold materials for bone tissue engineering are classified into inorganic materials (hydroxyapatite, tricalcium phosphate, bioglass, titanium, and magnesium), natural polymer materials (collagen, silk fibroin, and chitosan) and synthetic polymer materials (polycaprolactone, polylactic acid, polyglycolic acid and poly(lactic-co-glycolic acid)). The studies on materials that interact with cells to guide their biological response and bone differentiation are increasing. But how to create a safe, rational, and close to the micro-environment of cell growth in vivo is a challenge. Modification of bioscaffold materials can directly regulate osteogenic differentiation of stem cells. Moreover, vascularization and post-implantation infections are issues of concern.

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    Application and prospect of bone marrow mesenchymal stem cells in the treatment of early femoral head necrosis  

    Wang Tiantian, Wang Jianzhong
    2020, 24 (7):  1117-1122.  doi: 10.3969/j.issn.2095-4344.1863
    Abstract ( 421 )   PDF (676KB) ( 223 )   Save

    BACKGROUND: Femoral head necrosis is a common progressive disabling disease in orthopedics, and it is difficult to reverse disease progression. Eventually, the loss of hip function seriously impact patient’s quality of life.

    OBJECTIVE: To review the research progress of bone marrow mesenchymal stem cells in the treatment of femoral head necrosis.

    METHODS: The PubMed, CNKI and WanFang databases were searched for relevant articles with the keywords of “bone marrow mesenchymal stem cells, femoral head necrosis” in English and Chinese, respectively. The search time was from January 2001 to April 2019. Articles that were not related to the purpose of the research and repetitive articles were excluded, and 42 articles that met the criteria were finally included for review.

    RESULTS AND CONCLUSION: Bone marrow mesenchymal stem cells potentially repair the femoral head, not only providing precursor cells, but also secreting cytokines and growth factors and initiating cell healing in the femoral head. A large number of experimental and clinical studies have proved that bone marrow mesenchymal stem cells are available for the treatment of early femoral head necrosis.

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    Tissue repair using mesenchymal stem cells via mitochondrial transfer 
    Wang Zhangling, Yu Limei, Zhao Chunhua
    2020, 24 (7):  1123-1129.  doi: 10.3969/j.issn.2095-4344.2018
    Abstract ( 477 )   PDF (695KB) ( 121 )   Save

    BACKGROUND: Mesenchymal stem cells have been used in the treatment of various diseases due to their advantages, and mitochondrial transfer is an important mechanism of mesenchymal stem cell therapy.

    OBJECTIVE: To review the role of mesenchymal stem cells via mitochondrial transfer in various tissue injuries.

    METHODS: The key words were “stem cells, mitochondrial transfer, cell communication, rescue and repair, tissue injury” in English and Chinese, respectively. PubMed, CNKI and WanFang databases were retrieved for the articles published from 2008 to 2019. The articles concerning the mitochondrial transfer function and mechanism of mesenchymal stem cells and the treatment of tissue injury were collected. After removal of the repetitive and irrelevant articles, 64 eligible articles were further analyzed.

    RESULTS AND CONCLUSION: Mesenchymal stem cells have been used in stroke, myocardial infarction, and acute renal failure. Mitochondrial transfer has been widely recognized as a new mechanism of stem cell therapy and has been considered as a potential therapy for tissue injuries. Mitochondrial transfer has been found to be mediated by different modes, including tunnel tube formation, gap junctions, microvesicles, cell fusion and transfer of isolated mitochondria. However, specific mechanisms of mitochondrial transfer in tissue injury have not been fully elucidated and its specific role in tissue repair also needs further investigation.

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    Non-coding RNAs in human dental pulp stem cells: regulations and mechanisms
    Ren Chunmei, Liu Yufang, Xu Nuo, Shao Miaomiao, He Jianya, Li Xiaojie
    2020, 24 (7):  1130-1137.  doi: 10.3969/j.issn.2095-4344.2011
    Abstract ( 373 )   PDF (812KB) ( 149 )   Save

    BACKGROUND: Human dental pulp stem cells are important oral mesenchymal stem cells with strong proliferation and multidirectional differentiation functions. In-depth studies on the Human Genome Project make people gradually realize that functional non-coding RNAs play an extraordinary role in regulating gene expression.

    OBJECTIVE: To discuss the function and application of non-coding RNAs in human dental pulp stem cells.

    METHODS: Using “ncRNAs, human dental pulp stem cells, regenerative medicine” as keywords in English and Chinese, the first author searched PubMed, Medline, CNKI, and WanFang for relevant articles published from 2005 to 2019. Literatures unrelated to the purpose of the study and repetitive literatures were excluded, and 71 articles that meet the criteria were included for review.

    RESULTS AND CONCLUSION: It is now generally believed that non-coding RNAs can be used as a signal of specific cell state, providing prognostic value and even providing treatment options for patients. With the continuous development of regenerative medicine applications, human dental pulp stem cells are arousing increasing attentions. Exploration on the relationship between non-coding RNAs and human dental pulp stem cells provides a new approach for the clinical application of human dental pulp stem cells.

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    Pathogenesis of inflammatory bowel disease and mesenchymal stem cell therapy: therapeutic application and existing problems
    Huang Wenwen, Li Shuo, Hou Zongliu, Wang Wenju
    2020, 24 (7):  1138-1143.  doi: 10.3969/j.issn.2095-4344.1846
    Abstract ( 406 )   PDF (701KB) ( 276 )   Save

    BACKGROUND: In recent years, the incidence of inflammatory bowel disease is yearly increasing, and there are no effective treatment plans. Mesenchymal stem cells have achieved good outcomes in the treatment of immune-related diseases such as systemic lupus erythematosus, myocardial infarction and graft-versus-host disease. Numerous studies have shown that mesenchymal stem cells have their unique advantages in the treatment of inflammatory bowel disease. Therefore, increasing concern has been placed on the treatment of inflammatory bowel disease by mesenchymal stem cells.

    OBJECTIVE: To summarize the existing research on the treatment of inflammatory bowel disease by mesenchymal stem cells, and to discuss its application and safety.

    METHODS: “Mesenchymal stem cells, inflammatory bowel disease, pathogenesis, treatment” were used as keywords to search CNKI, WanFang and PubMed databases for relevant literatures in the past 20 years both in Chinese and English. Finally, 62 papers were selected for review.

    RESULTS AND CONCLUSION: Mesenchymal stem cells have the abilities of self-renewal, tissue migration and pluripotency, as well as strong immunomodulatory effects. They not only show satisfying therapeutic effects in systemic lupus erythematosus, myocardial infarction, graft-versus-host disease and other immune-related diseases, but also have promising prospects in inflammatory bowel disease. However, little is reported in clinical studies, and there are still many problems, such as safety, encountered in the treatment of inflammatory bowel disease with mesenchymal stem cells.

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    A bibliometric analysis on articles, authors and high-impact institutions in the field of pluripotent stem cells based on data from Scopus  

    He Lin, Bai Jinwei, Su Wei
    2020, 24 (7):  1144-1148.  doi: 10.3969/j.issn.2095-4344.2013
    Abstract ( 346 )   PDF (709KB) ( 47 )   Save

    BACKGROUND: Pluripotent stem cells have brought a new light for treating many diseases, and countries are increasing their investment and attention in this field.

    OBJECTIVE: To provide reference for Chinese institutions or authors engaged in pluripotent stem cells, so as to promote the quality and international competitiveness in this research field.

    METHODS: A retrospective retrieval was performed using the keywords “pluripotent stem cell” OR “pluripotential stem cell” OR “multipotent stem cell” OR “multipotential stem cell” for the articles concerning pluripotent stem cells published from 2014 to 2018 in the Scopus database published by Elsevier. The retrieved articles were analyzed by using SciVaL and Microsoft Excel 2007. It revealed the scholars and institutions of the articles, high-impact papers and research status in China.

    RESULTS AND CONCLUSION: (1) From 2014 to 2018, the Scopus database contains a total of 18 508 articles addressing pluripotent stem cells. Its Field-Weighted Impact Factor is 1.43, its medical discipline output is 6 398, and its Field-Weighted Citation Impact is 1.38. 27.7% of the articles are highly cited, 48.4% of the articles are published in highly influential journals, and 27% of the articles are completed by international cooperation. (2) The institution with the largest number of publications is 805 articles at Harvard University, with a total of 1 732 authors and a total of 21 654 citations. The Chinese Academy of Sciences ranks fourth in terms of volume, publishing 394 articles and 1 139 authors, with a total of 5 313 citations. (3) The most published individual was Professor JOSEPH from Stanford University, 117 articles, total cited 2 878 times, H-index 74. (4) Of the 5 papers cited greater than 500 times, 2 are reviews and 3 original researches. Six Japanese institutions are in the top 10 in Asia, followed by three in China and one in India. The author of the most published articles in China is Professor Pei Duanqing, who has published 45 articles with a total of 864 citations. (5) In summary, in 2014-2018, Harvard University in the United States takes the lead, with evident output and influence. The United States and Japan each account for 3 of the top 10 scholars and Germany holds two, while Chinese influential scholars or institutions in the field have yet to work. Comprehensive analysis of high-impact research institutions, research authors, and research articles provides forward-looking thinking for scientific research in the field of pluripotent stem cells.

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