Loading...

Table of Content

    18 June 2019, Volume 23 Issue 17 Previous Issue    Next Issue
    For Selected: Toggle Thumbnails
    Intravenous administration of bone marrow mesenchymal stem cells protects liver function following fatty liver transplantation from donors after cardiac death
    Cai Qiucheng, Fan Hongkai, Xiong Rihui, Jiang Yi
    2019, 23 (17):  2625-2629.  doi: 10.3969/j.issn.2095-4344.1683
    Abstract ( 370 )   PDF (1115KB) ( 94 )   Save

    BACKGROUND: Liver transplantation from donation after cardiac death triggers a significant increase in the incidence of complications after transplantation due to the high incidence of fatty liver, long-term warm ischemia time and low perfusion time. Theoretically, mesenchymal stem cells can promote the regeneration of transplanted organ cells, and reduce ischemia-reperfusion injury as well as various immune damages after organ transplantation, thus protecting the function of transplanted organs.
    OBJECTIVE: To study the effect of bone marrow mesenchymal stem cells on liver function undergoing liver transplantation from donors after cardiac death.
    METHODS: Rat bone marrow mesenchymal stem cells were isolated, cultured and purified by density gradient centrifugation. The donor rats were reared to moderate-severe fatty liver, and induced cardiac death. Recipient rats were randomized into three groups: (1) control group (n=10), fatty donor liver transplantation from donation after cardiac death; (2) negative control group (n=10), fatty donor liver transplantation from donation after cardiac death plus injection of 1 mL normal saline through the portal vein; and (3) experimental group, fatty donor liver transplantation from donation after cardiac death plus injection of 1 mL PBS containing bone marrow mesenchymel stem cells (approximately 1.0×106 cells). The serum transaminase levels were evaluated at 1, 3, and 7 days after liver transplantation. Apoptosis of hepatocytes was detected using TUNEL.
    RESULTS AND CONCLUSION: (1) On the 1st day after transplantation, there was no significant difference in the transaminase level among the three groups. On the 3rd and 7th days after transplantation, the levels of transaminase in the experimental group were significantly lower than those in the control group and negative control group (P < 0.05). (2) The apoptotic index of hepatocytes in the experimental group was significantly lower than that in the control group and the negative control group (P < 0.01); however, there was no significant difference between the control group and the negative control group (P > 0.05). To conclude, bone marrow mesenchymal stem cell transplantation can inhibit the apoptosis in hepatocytes and make liver function recover quickly following fatty liver transplantation from donors after cardiac death.

    Figures and Tables | References | Related Articles | Metrics
    Exosomes derived from human umbilical cord mesenchymal stem cells promote myocardial repair after myocardial infarction under hypoxia
    Zhang Pin, Guo Ying, Gao Yajie, Wang Zhendong, Li Baiyi, Zhang Xiaomin, Niu Yuhu, Liu Zhizhen, Ma Lihui, Niu Bo, Guo Rui
    2019, 23 (17):  2630-2636.  doi: 10.3969/j.issn.2095-4344.1716
    Abstract ( 347 )   PDF (785KB) ( 232 )   Save

    BACKGROUND: Studies have shown that exosomes are an important mechanism of stem cell therapy for myocardial infarction. Hypoxic preconditioning affects the quantity and content of exosomes from human umbilical cord mesenchymal stem cells.
    OBJECTIVE: To compare the effects of exosomes derived from human umbilical cord mesenchymal stem cells pretreated with hypoxia and cultured with normoxia on myocardial repair after myocardial infarction in rats, and to explore the possible mechanisms.
    METHODS: (1) Human umbilical cord mesenchymal stem cells isolated from healthy newborn umbilical cord were cultured for fourth generations and identified. Passage 4 human umbilical cord mesenchymal stem cells with fusion degree of 50%-60% were pretreated for 48 hours in combination with serum-free medium and oxygen gradient culture (hypoxia and normoxia). Exosomes were then extracted from two sets of cell culture supernatants by ultracentrifugation. (2) Fifty Sprague-Dawley female rats provided by the Experimental Animal Center of Shanxi Medical University in China were enrolled, 40 of which were used to make animal models of myocardial infarction and the remaining 10 rats were subjected to sham operation. After successful modeling, 30 model rats were randomly assigned into model group, hypoxic exosomes group, normoxic exosomes group (n=10/group). One week after myocardial infarction, the heart was opened again, and the same volume of exosomes or PBS was injected at four points around the infarct area (the whitening area), 25 μL per point, 100 μL for each rat. One week after transplantation, echocardiography was performed to measure cardiac function. After completion of echocardiography, heart samples were taken and pathological sections were prepared for hematoxylin-eosin staining and Masson staining. Western blot assay was used to detect the expression of apoptosis-related proteins Cleaved-caspase 3 and Bcl-2.
    RESULTS AND CONCLUSION: (1) One week after exosomes transplantation, the ejection fraction and fractional shortening rate of the left ventricle in hypoxic exosomes and normoxic exosomes groups significantly increased (P < 0.01), while left ventricular end-diastolic diameter and left ventricular end-systolic diameter significantly decreased (P < 0.01). The above indexes improved most significantly in the hypoxic exosomes group (P < 0.01). (2) Hematoxylin-eosin staining results showed that the cells were in alignment in the sham-operated group. Most serious lesions were found in the model group. The hypoxic exosomes group had less lesions than the normoxic exosomes group. (3) Masson staining results showed that the compared with the model group, the collagen volume fraction was decreased significantly in the two exosomes groups, especially in the hypoxic exosomes group (P < 0.01). (4) Western blot results showed that compared with the model group, the expression of Cleaved-caspase-3 decreased while the expression of Bcl-2 increased in the hypoxic and normoxic exosomes groups, and the variation in the protein expression was more obvious in the hypoxic exosomes group than the normoxic exosomes group (P < 0.01). To conclude, these findings reveal that exosomes derived from human umbilical cord mesenchymal stem cells under hypoxia can improve myocardial repair in Sprague-Dawley rats with myocardial infarction.

    Figures and Tables | References | Related Articles | Metrics
    Characteristics of bone marrow mesenchymal stem cells in a rat model of retinoic acid-induced osteoporosis
    Long Yanming, Xie Mengsheng, Xue Wenli, Huang Jiajie, Li Xiaojie
    2019, 23 (17):  2637-2643.  doi: 10.3969/j.issn.2095-4344.1703
    Abstract ( 228 )   PDF (909KB) ( 103 )   Save

    BACKGROUND: Retinoic acid has been directly used to intervene with bone marrow mesenchymal stem cells in vitro; however, there is still a lack of research on in vitro characteristics of bone marrow mesenchymal stem cells in an osteoporosis rat model induced by retinoic acid.
    OBJECTIVE: To establish the osteoporosis rat model induced by retinoic acid and to observe the characteristics of bone marrow mesenchymal stem cells from the rat model in vitro
    METHODS: Sprague-Dawley rats were randomly divided into two groups. The experimental group was treated with retinoic acid, 70 mg/kg per day for 2 weeks, in order to quickly establish osteoporosis models, while the control group was given an equal volume of normal saline. Bone marrow mesenchymal stem cells were cultured using the whole bone marrow culture method in vitro and their characteristics (cell morphology, growth curve and surface antigens) were observed. After osteogenic induction, the in vitro mineralization capacity and alkaline phosphatase secretion capacity of the cells were measured. After adipogenic induction, the adipogenic ability of cells was detected.
    RESULTS AND CONCLUSION: (1) Morphology of bone marrow mesenchymal stem cells was basically the same in the two groups. The proliferation capacity of the cells in the experimental group was higher than that in the control group at 9 days after culture. (2) After osteogenic induction, the alkaline phosphatase activity in the experimental group was lower than that in the control group (P < 0.05), which was consistent with the results of alizarin red staining and alkaline phosphatase staining. (3) After adipogenic induction, larger number of lipid droplets and higher absorbance value for oil red O could be observed in the experimental group than the control group (P < 0.05). To conclude, bone marrow mesenchymal stem cells from the osteoporosis rat model induced by retinoic acid have lower osteogenic capacity but higher adipogenic capacity than the normal cells.

    Figures and Tables | References | Related Articles | Metrics
    Osteogenic and angiogenic ability of bone marrow mesenchymal stem cells synergistically over-expressing hypoxia-inducible factor-1α and bone morphogenetic protein-6 genes under hypoxia
    Liao Hongxing, Zhang Zhihui, Liu Zhanliang, Huang Jian, Shen Yeguang, Huang Yingmei, Zhong Zhixiong
    2019, 23 (17):  2644-2650.  doi: 10.3969/j.issn.2095-4344.1701
    Abstract ( 341 )   PDF (914KB) ( 112 )   Save

    BACKGROUND: Hypoxia-inducible factor-1α (HIF-1α) is currently considered to be one of the most important regulators of oxygen homeostasis in the body. Bone morphogenetic protein-6 (BMP-6) is one of the most osteogenic bone morphogenetic proteins. In this study we attempted to construct bone marrow mesenchymal stem cell (BMSC) lines co-expressing HIF-1α and BMP-6 to explore the tolerance and functional benefit of the cells under hypoxic conditions.
    OBJECTIVE: To investigate the proangiogenic and osteogenic ability of BMSCs synergistically over-expressing HIF-1α and BMP-6 under hypoxic environment in vitro.
    METHODS: BMSCs were isolated, cultured and identified from Sprague-Dawley rats. BMSCs co-overexpressing HIF-1α and BMP-6 were constructed by adeno-associated viral vector. aav-HIF-1α-BMP-6-BMSCs were cultured under normoxia (21% O2) and hypoxia (2% O2), and non-transfected BMSCs under normoxia were used as a control group. mRNA levels of HIF-1α, VEGF, BMP-6, GLUT-1, SIRT-1, OCN, RUNX2, AKP were detected by RT-qPCR. After co-culture of BMSCs and human umbilical vein endothelial cells, the in vitro tube formation ability was observed. After osteogenic induction, alkaline phosphatase staining and alizarin red staining were used to identify the osteogenic effect of the cells.
    RESULTS AND CONCLUSION: (1) Flow cytometry results showed that BMSCs at passage 4 highly expressed CD29, CD90 and CD44, but lowly expressed CD45, CD11 and CD34. (2) The expression levels of VEGF, GLUT-1, SIRT-1, OCN, RUNX2, and AKP mRNA in the hypoxia group were significantly higher than those in the normoxia group (P < 0.01). (3) In vitro tube formation assay results showed that the number of tubules formed in the hypoxia group was significantly higher than that in the normoxia group (P < 0.01). (4) More calcium nodules and round mineralized nodules appeared in the hypoxia group than in the normoxia group. These findings suggest that BMSCs co-expressing HIF-1α and BMP-6 can promote the osteogenic and angiogenic ability under hypoxia in vitro.

    Figures and Tables | References | Related Articles | Metrics
    Isolation and identification of exosomes from human adipose-derived mesenchymal stem cells
    Wang Jing, Cai Xia, Wang Zhiguo, Xu Quanchen, Li Kun, Hua Cheng
    2019, 23 (17):  2651-2658.  doi: 10.3969/j.issn.2095-4344.1715
    Abstract ( 442 )   PDF (617KB) ( 187 )   Save

    BACKGROUND: Adipose-derived mesenchymal stem cells as one of the important seed cells can be extracted in large quantities by simple methods. However, clinical application of the cells is limited by rigorous storage conditions and inconvenient transportation. Exosomes can be secreted by adipose-derived mesenchymal stem cells, whose structure is stable and difficult to decompose, providing new possibilities for clinical application of adipose-derived mesenchymal stem cells.
    OBJECTIVE: To isolate and identify human adipose-derived mesenchymal stem cells and induce multidirectional differentiation of the cells as well as to isolate and identify the exosomes from adipose-derived mesenchymal stem cells.
    METHODS: Adipose-derived mesenchymal stem cells were isolated from superficial abdominal subcutaneous adipose tissue of normal adult women after liposuction. The cells were purified by cell adherence method. The cells were digested and passaged by trypsin. The third generation cells were identified by flow cytometry, followed by adipocyte induction and identification as well as osteoblast induction and identification. Adipose-derived mesenchymal stem cells of the 3rd to 6th generations were collected. The exosomes were extracted from cell supernatant by differential centrifugation. The protein concentration was measured by BCA. The morphology of the exosomes was observed by transmission electron microscopy. The diameter distribution of the exosomes was measured by particle size analyzer. The exosomes were identified by immunomagnetic beads and flow cytometry.
    RESULTS AND CONCLUSION: Adipose-derived mesenchymal stem cells were long spindle-shaped, fibroblasts-like, when arranged tightly. Flow cytometry showed that adipose-derived mesenchymal stem cells were positive for CD29, CD44, CD90 and CD105, but negative for CD34 and CD45. Alkaline phosphatase staining was blue-purple on the 9th day after induction of osteoblasts. Alizarin red S staining showed red calcium nodules in the extracellular matrix on the 21st day after induction. Oil red O staining was orange on the 14th day after induction of adipocytes. Under the transmission electron microscope the exosome was cup-shaped with a diameter of (81.225±22.226) nm and had a membrane structure. The protein concentration was about 1.5 g/L and the diameter distribution ws concentrated in 70-100 nm. Flow cytometry showed that the exosomes were positive for CD9, CD29, CD44, CD63, CD90 and CD105, but negative for CD34 and CD45. To conclude, the exosomes derived from adipose-derived mesenchymal stem cells can be successfully extracted by ultracentrifugation and identified by transmission electron microscopy, immunomagnetic beads and flow cytometry.

    Figures and Tables | References | Related Articles | Metrics
    Lentiviral-mediated shRNA silencing of Notch-1 inhibits expression of Notch signaling pathway in rat bone marrow mesenchymal stem cells
    Yan Jinyu, Xing Wanhong
    2019, 23 (17):  2659-2664.  doi: 10.3969/j.issn.2095-4344.1704
    Abstract ( 332 )   PDF (892KB) ( 103 )   Save

    BACKGROUND: Number studies have insight into the mechanism of Notch signaling pathway in the differentiation of bone marrow mesenchymal stem cells into cardiomyocytes, but the mechanism of silencing Notch signaling pathway in the engineered myocardial-like tissue vascular network is less elucidated.
    OBJECTIVE: To investigate the role of Notch signaling pathway in bone marrow mesenchymal stem cells in the construction of engineered myocardial-like tissue vascular network.
    METHODS: The lentivirus expression vector was constructed by pLV[shRNA]-EGFP: T2A: Puro-U6] {rNotch1 [shRNA]_19 nt}(PLV-Notch) and pLV[shRNA]-EGFP: T2A: Puro-U6>Scramble_shRNA(PLV-Scramble) and packaged with the lentivirus vector. The mixture was co-transfected into HEK-293 T cells. The lentivirus suspension was collected and the titer of recombinant virus was detected by quantitative PCR. The constructed PLV-Notch and PLV-Scramble were infected with bone marrow mesenchymal stem cells respectively. The expression of enhanced green fluorescent protein gene and target gene rNotch1 in the transfected cells was identified by fluorescence microscopy, RT-qPCR and western blot.
    RESULTS AND CONCLUSION: The titer of lentivirus vector was more than 1×108 TU/mL. The mature cell lines were screened. The fluorescence rate of the two transfection groups was 80%, and the expression of rNotch1 gene in the interference group was 75.2% of that in the scrambled group. Therefore, lentiviral-mediated rNotch1 gene transfection of bone marrow mesenchymal stem cells can be successfully constructed and silence the expression of Notch signal pathway.

    Figures and Tables | References | Related Articles | Metrics
    Effects of ursolic acid on proliferation and differentiation of bone marrow mesenchymal stem cells
    Liu Yaohui, Huang Zhenming, He Jingxuan, Huang Linghua, Li Jianping
    2019, 23 (17):  2665-2671.  doi: 10.3969/j.issn.2095-4344.1729
    Abstract ( 390 )   PDF (801KB) ( 123 )   Save

    BACKGROUND: Ursolic acid can inhibit the proliferation and differentiation of osteoclasts through Wnt signaling pathway, to exert anti-inflammatory and osteoprotective effects in rats with collagen-induced arthritis. However, it is unclear about the effects of ursolic acid on proliferation and differentiation of rat bone marrow mesenchymal stem cells and expression of Wnt/β-catenin signaling pathway-related genes and proteins.
    OBJECTIVE: To investigate the effects of ursolic acid on proliferation, differentiation and Wnt signaling pathway of bone marrow mesenchymal stem cells. 
    METHODS: Rat bone marrow mesenchymal stem cells were cultured in vitro by whole bone marrow adherence method, and then different concentrations of ursolic acid (1.0, 2.5, 5.0, 10.0, 20.0 μmol/L) acted on the cells. Cells with no treatment of ursolic acid were used as control group. MTT assay was used to detect the effect of ursolic acid on the proliferation of bone marrow mesenchymal stem cells. Differentiation of bone marrow mesenchymal stem cells was induced by osteogenic induction solution containing different concentrations of ursolic acid (1.0, 2.5, 5.0 μmol/L). Cells cultured in the osteogenic induction medium with no ursolic acid. Alkaline phosphatase activity and osteocalcin level were detected by ELISA at 7 and 14 days. RT-PCR was used to detect the mRNA levels of ALP, COL-I, OCN, OPN and RUNX2. The expressions of Wnt-3α, GSK-3β and β-catenin mRNAs and proteins related to Wnt signaling pathway were detected by RT-PCR and western blot, respectively. 
    RESULTS AND CONCLUSION: (1) Different concentrations of ursolic acid could promote the proliferation of bone marrow mesenchymal stem cells, and the proliferative rate was highest when the cells were treated with 5.0 μmol/L ursolic acid. (2) Compared with the control group, the alkaline phosphatase activity and osteocalcin level were significantly higher at 7 and 14 days after osteoinduction (P < 0.05), and the alkaline phosphatase activity and osteocalcin level increased with the increasing concentration of ursolic acid. (3) At 14 days after osteoinduction, ursolic acid promoted the expression of osteogenic genes ALP, COL-I, OCN, OPN, RUNX2 mRNAs and Wnt signaling pathway-related Wnt-3α, GSK-3β and β-catenin mRNAs and proteins and the expression levels increased with the increasing concentration of ursolic acid (P < 0.05). To conclude, ursolic acid can promote the differentiation of bone marrow mesenchymal stem cells into osteoblasts via Wnt/β-catenin signaling pathway.

    Figures and Tables | References | Related Articles | Metrics
    Distribution of Sca-1+ adult stem cells along the linea alba of mice
    Hao Yuhui, Liu Zhizhen, Liu Dan, Feng Yujuan, Xie Jun
    2019, 23 (17):  2672-2677.  doi: 10.3969/j.issn.2095-4344.1721
    Abstract ( 970 )   PDF (917KB) ( 130 )   Save

    BACKGROUND: The interaction between stem cells and meridians and collaterals is still in the stage of theoretical research, and it is urgent to conduct relevant scientific experiments.
    OBJECTIVE: To observe the distributions of Sca-1+ adult stem cells in the fat tissues of murine linea alba, providing an experimental basis for further studying the interaction of stem cells with meridians and collateral channels. 
    METHODS: Balb/c mice were selected to observe the morphological characteristics of any Ren-meridian circulation regions along the anterior midline of the subcutaneous chest of the mice through stereomicroscopy and hematoxylin-eosin staining. Linea alba, the abdomen landmark of Ren-meridian, was selected as the objective of our study. Morphologies of tissues from linea alba were observed by stereomicroscope, hematoxylin-eosin staining, oil red O staining and Masson staining. Distribution of Sca-1+ adult stem cells from fat tissues in the linea alba was observed by immunohistochemical staining and multiple slices. 
    RESULTS AND CONCLUSION: (1) In the study, we firstly observed that the fat tissues presented with band-like distribution in Ren-meridian circulation regions along the anterior midline of the subcutaneous chest of mice. (2) We firstly found that murine linea alba was made of fat tissues. (3) We firstly observed that Sca-1+ adult stem cells were distributed along the linea alba, the abdomen landmark of Ren-meridian. The present study preliminarily investigated the Sca-1+ adult stem cells in the linea alba part of Ren-meridian. This attempt may provide an experimental basis and idea for the exploration of functions of stem cells and Ren-meridian.

    Figures and Tables | References | Related Articles | Metrics
    Bone repair using skeletal muscle stem cells combined with platelet-rich plasma
    Yin Nuo, Xue Feng, Xiao Haijun, Ding Liang, Yuan Junjie, Pan Mingmang, Yu Du, Ju Jinyong, Zhu Longzhang
    2019, 23 (17):  2678-2683.  doi: 10.3969/j.issn.2095-4344.1719
    Abstract ( 265 )   PDF (850KB) ( 171 )   Save

    BACKGROUND: Platelet-rich plasma contains a variety of active factors, which has certain advantages as a cytokine that promotes stem cell differentiation for bone tissue engineering.
    OBJECTIVE: To investigate the effect of skeletal muscle stem cells combined with platelet-rich plasma to promote the repair of rabbit bone.
    METHODS: (1) Rabbit platelet-rich plasma was prepared and skeletal muscle stem cells from rabbit soleus muscle were isolated. Twenty-eight New Zealand white rabbits were randomly divided into four groups (n=7/group), in which the proximal humeral bone defect model was prepared in each rabbit, followed by implantation of nothing (natural healing group), allogeneic skeletal muscle stem cells, autologous platelet-rich plasma or platelet-rich plasma combined with skeletal muscle stem cells, respectively. CT and histological examinations were performed to detect bone healing postoperatively.
    RESULTS AND CONCLUSION: In the postoperative 4-week CT film, new bone formation was faster in the combination group than the other three groups (P < 0.05). No significant difference in the bone formation rate was observed in the skeletal muscle stem cell and platelet-rich plasma groups (P > 0.05), but the bone formation rate in these two groups was significantly better than that in the natural healing group (P < 0.05). (2) Histological score of the one defect specimens was highest in the combination group and lowest in the natural healing group, and there was no significant difference between the skeletal muscle stem cell and platelet-rich plasma groups. These results reveal that both platelet-rich plasma and skeletal muscle stem cells could promote bone repair, and their combination could achieve better outcomes in bone repair.

    Figures and Tables | References | Related Articles | Metrics
    Protective effects of different doses of vascular endothelial growth factors on neural stem cells under hypoxic environment
    Zhou Jingxia, Chen Lin, Chen Bocan, Xing Huaijie, Yan Limin, Zeng Chaosheng, Wu Hairong, Huang Yusheng, Chen Jiegui
    2019, 23 (17):  2684-2689.  doi: 10.3969/j.issn.2095-4344.1709
    Abstract ( 333 )   PDF (770KB) ( 299 )   Save

    BACKGROUND: Vascular endothelial growth factor (VEGF) is a cytokine which can promote angiogenesis. Recently, some animal experiments and clinical studies have shown that VEGF expression is increased in acute ischemic stroke and spinal cord injury, which can inhibit cell apoptosis, but the mechanism is not clear.
    OBJECTIVE: To intervene in hypoxic-induced neural stem cells with different doses of VEGF, and to explore the protective effects and mechanism of VEGF.
    METHODS: Neural stem cells was obtained from the cerebral cortex of a fetal rat, which were randomly divided into blank control group, hypoxia group and low-, medium- and high-dose VEGF groups. The cells in the blank control group were cultured for 24 hours under 35% oxygen. The cells in the other four groups were cultured for 24 hours under 3% oxygen. In the low-, medium- and high-dose VEGF groups, 20, 40 and 80 μmol/L VEGF were supplemented into the medium, respectively. The proliferation and apoptosis of the cells were detected by cell counting kit-8 method and TUNEL method. The expression level of nerve cell apoptosis related proteins was detected by western blot.
    RESULTS AND CONCLUSION: Compared with the blank control group, the proliferation of neural stem cells decreased, the number of apoptotic neural stem cells was increased significantly, the expression levels of Bcl-2 and nuclear factor κB in the cells were decreased, and the expression levels of Bax and TWIK were increased in the hypoxia group. VEGF at all the three doses could inhibit these phenomena, and 40 μmol/L VEGF showed the best efficacy. These results indicate that VEGF can affect cell apoptosis by interfering with the expression of apoptosis-related proteins, and then exert neuroprotective effects, especially at 40 μmol/L.

    Figures and Tables | References | Related Articles | Metrics
    Protective effect of human umbilical cord mesenchymal stem cells on acute drug-induced liver injury after conditioning in haploidentical hematopoietic stem cell transplantation
    Wang Xiaoning, Chen Ying, Zhu Huachao, Zhang Mei, He Pengcheng
    2019, 23 (17):  2690-2695.  doi: 10.3969/j.issn.2095-4344.1717
    Abstract ( 372 )   PDF (668KB) ( 151 )   Save

    BACKGROUND: Haploidentical hematopoietic stem cell transplantation is currently the mainstream mode of transplantation in China, but its widespread development is restricted by the higher incidence of graft-versus-host disease and implantation failure as compared with HLA identical hematopoietic stem cell transplantation. In order to solve these two problems, co-transplantation of mesenchymal stem cells and hematopoietic stem cells is used in some transplant centers to promote hematopoietic stem cell transplantation, and to reduce the incidence of graft-versus-host disease. Studies have shown that mesenchymal stem cells can promote the repair of liver cells in liver cirrhosis and hepatitis patients. It is unclear whether co-transplantation of mesenchymal stem cells and hematopoietic stem cells can prevent acute drug-induced liver injury.
    OBJECTIVE: To investigate the preventive and protective effects of infusion of umbilical cord blood mesenchymal stem cells on acute drug-induced liver injury after conditioning in haploidentical hematopoietic stem cell transplantation. 
    METHODS: Clinical data of patients who underwent haploidentical hematopoietic stem cell transplantation from January 2010 to August 2017 was retrospectively analyzed. Eight cases were transfused with umbilical cord blood mesenchymal stem cells 1×106/kg within 4-6 hours before transfusion of hematopoietic stem cells. Seventeen-seven cases in the control group were not given umbilical cord blood mesenchymal stem cells. The changes of liver function indicators and treatment outcomes at 1 day, 2 weeks and 4 weeks after transplantation conditioning were observed. The study protocol was approved by the ethics committee of the First Affiliated Hospital of Xi’an Jiao Tong University with the approval No. 2016(20). Written informed consent was obtained prior to the initiation of the study. 
    RESULTS AND CONCLUSION: (1) Patients in both groups had abnormalities in the biomedical indicators of liver function to different extent. These indicators peaked at 2 weeks post preconditioning, and then became normal after 4 weeks. (2) The levels of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, transglutaminase, and direct bilirubin were significantly lower in the observation group than the control group at 1 day and 2 weeks after transplantation conditioning (P < 0.05). (3) There were no adverse reactions such as fever, blood pressure increase/decrease, arrhythmia and hemolysis in the two groups during the infusion of hematopoietic stem cells and umbilical cord blood mesenchymal stem cells. These findings reveal that co-transfusion of umbilical cord blood mesenchymal stem cells during haploidentical hematopoietic stem cell transplantation may reduce acute drug-induced liver injury after transplantation conditioning, and it needs to be further investigated duo to limit numbers of patients.

    Figures and Tables | References | Related Articles | Metrics
    Intervention with autologous adipose-derived mesenchymal stem cells for immune function in mice with systemic lupus erythematosus
    Ye Ling, Zhu Jing, He Chengsong
    2019, 23 (17):  2696-2702.  doi: 10.3969/j.issn.2095-4344.1708
    Abstract ( 362 )   PDF (953KB) ( 112 )   Save

    BACKGROUND: Although mesenchymal stem cells have achieved clinical efficacy in the treatment of systemic lupus erythematosus, the endogenous function and immunomodulatory mechanism of the cells need to be further studied. 
    OBJECTIVE: To investigate the effect of autologous adipose-derived mesenchymal stem cells on immune function in mice with systemic lupus erythematosus and its possible mechanism. 
    METHODS: Thirty-six MRL/lpr mice were randomly divided into three groups: model control group without treatment, PBS control group with tail vein injection of PBS, and stem cell transplantation group with tail vein injection of autologous adipose-derived mesenchymal stem cells. Another 12 C57BL/6 mice were taken as normal control group.
    RESULTS AND CONCLUSION: (1) The cells obtained from autologous adipose tissue of MRL/lpr mice had the characteristics of adipose-derived mesenchymal stem cells. (2) The levels of serum urea nitrogen, creatinine and anti-double-stranded DNA antibodies in the model control group, PBS control group and stem cell transplantation group were higher than those in the normal control group (P < 0.01). The levels of serum urea nitrogen, creatinine and anti-double-stranded DNA antibody in the stem cell transplantation group were lower than those in the model control group and PBS control group (P < 0.05). (3) The positive rates of peripheral blood regulatory T cells in the model control group and PBS control group were lower than those in the normal control group and stem cell transplantation group, and the positive rate of peripheral blood regulatory T cells in the stem cell transplantation group was lower than that in the normal control group (P < 0.01). (4) The positive rates of splenic dendritic cells in the model control group and PBS control group were lower than those in the normal control group and stem cell transplantation group (P < 0.01). (5) Th2 ratio in the model control group, PBS control group and stem cell transplantation group was higher than that in the normal control group (P < 0.05). Th1 ratio and Th1/Th2 ratio in the model control group and PBS control group were lower than those in the normal control group and stem cell transplantation group (P < 0.05). (6) Compared with the normal control group, the levels of interleukin-2, interferon-γ, interleukin-10 and lymphotoxin in the peripheral blood of model control group and PBS control group decreased, while the level of interleukin-4 increased (P < 0.05). Compared with the model control group and PBS control group, the levels of interleukin-2, interleukin-10, interferon-γ and lymphotoxin in the peripheral blood of the stem cell transplantation group increased, while the level of interleukin-4 decreased (P < 0.05). In conclusion, adipose-derived mesenchymal stem cell transplantation can exert effects on the immune function of mice with systemic lupus erythematosus by increasing the proportions of dendritic cells and regulatory T cells and promoting the transformation of helper T lymphocyte subsets.

    Figures and Tables | References | Related Articles | Metrics
    CNE2 stem-like cells of nasopharyngeal carcinoma have stem cell characteristics and high level of autophagy
    Dai Senlin, Li Xiaoqian, Wu Jie, Yue Changwu, Li Yajun
    2019, 23 (17):  2703-2708.  doi: 10.3969/j.issn.2095-4344.1718
    Abstract ( 381 )   PDF (791KB) ( 120 )   Save

    BACKGROUND: Nasopharyngeal carcinoma is a head and neck malignant tumor with high invasion and metastatic potential. It has not yet achieved satisfactory effects in the treatment of advanced nasopharyngeal carcinoma. Some autophagy inhibitors and anti-tumor drugs have been used in clinical research, but the possible mechanism has not been clarified.
    OBJECTIVE: To explore whether high-level autophagy occurs in stem-like cells of nasopharyngeal carcinoma.
    METHODS: Tumor stem-like cell spheres were enriched from humanized nasopharyngeal carcinoma CNE2 cell line by serum-free suspension culture. The stem cell characteristics and expression levels of autophagy-related genes and proteins in CNE2 parental cells and CNE2 stem-like cells were detected using cell differentiation assay, flow cytometry, transmission electron microscope, western blot and RT-PCR. 
    RESULTS AND CONCLUSION: The nasopharyngeal carcinoma CNE2 stem-like cells were enriched by serum-free suspension culture. The suspension spheres were cultured in serum-containing medium to differentiate into CNE2 parental cells. Proportion of CD133+ cells in CNE2 stem-like cells (9.6%) was significantly higher than that in CNE2 parental cells (0.3%; P < 0.01). Compared with CNE2 parental cells, CNE2 stem-like cells highly expressed stemness-related genes Bmi-1, Twist1 and autophagy-related genes Beclin1 and LC3B (P < 0.01). Under the transmission electron microscope, the autophagic bodies of CNE2 stem-like cells in nasopharyngeal carcinoma were significantly increased compared with CNE2 parental cells. Therefore, nasopharyngeal carcinoma CNE2 stem-like cells can be effectively enriched using the serum-free suspension culture method, and be verified to have the biological characteristics of stem cells and exhibit high-level autophagy.

    Figures and Tables | References | Related Articles | Metrics
    Lentiviral-mediated transplantation of olfactory ensheathing cells modified by ciliary neurotrophic factor for treatment of spinal cord injury
    Ma Jiehua, Zhang Dan, Huo Yanli, Wei Yawei, Sun Lin, Zhao Yu
    2019, 23 (17):  2709-2715.  doi: 10.3969/j.issn.2095-4344.1723
    Abstract ( 454 )   PDF (1060KB) ( 166 )   Save

    BACKGROUND: Previous studies have confirmed that both ciliary neurotrophic factor and olfactory ensheathing cells have a certain therapeutic effect on spinal cord injury, but there is no report on whether their combination treatment has a better therapeutic effect.
    OBJECTIVE: To explore the effect of lentiviral-mediated transplantation of olfactory ensheathing cells modified with ciliary neurotrophic factor gene in rats with spinal cord injury and its related mechanisms. 
    METHODS: (1) In vitro experiment: There were four groups in the in vitro experiment: spinal cord neurons in control group and model group were cultured alone, while in overexpression co-culture group and normal co-culture group, Transwell chamber was used to establish the co-culture model of spinal cord neurons and olfactory ensheathing cells modified by ciliary neurotrophic factor gene or not. Alginate was given to damage the cells in the latter three groups. After 12 hours of co-culture, cell counting kit-8 assay was used to detect cell viability; qRT-PCR and western blot were used to detect the expression of BAX, BCL-2, Caspase 3 and ciliary neurotrophic factor in spinal neurons. (2) In vivo experiment: There were four groups in the in vivo experiment: sham operation group, model group, treatment group, and combination treatment group. Modified Allen’s method was used to make the rat model of spinal cord injury in the latter three groups. At 1 week after modeling, 5 µL of olfactory ensheathing cell suspension or ciliary neurotrophic factor overexpressing olfactory ensheathing cell suspension was injected 1 mm above and below the injured site in the treatment and combination treatment groups, respectively; similarly, the same volume of culture medium was given in the sham operation and model groups. At 4 weeks after treatment, Basso, Beattie and Bresnahan score and grid-climbing test were conducted to evaluate the motor ability of rats; hematoxylin-eosin staining was used to detect the pathological progression of spinal cord injury; and qRT-PCR and western blot were used to detect the expression of BAX, BCL-2, Caspase 3 and ciliary neurotrophic factor in spinal cord tissues. 
    RESULTS AND CONCLUSION: Olfactory ensheathing cells modified with ciliary neurotrophic factor gene could significantly alleviate cell injury and spinal cord injury (P < 0.001), increase the expression of ciliary neurotrophic factor (P < 0.01) and decrease the expression of apoptosis-related molecules BAX, BCL-2 and Caspase 3 (P < 0.01). To conclude, transplantation of olfactory ensheathing cells modified by ciliary ganglion neurotrophic factor gene can improve the motor function after spinal cord injury, which may be related to the down-regulation of BAX, BCL-2 and Caspase-3 expression and reduction in the apoptosis of spinal cord neurons.

    Figures and Tables | References | Related Articles | Metrics
    Zoledronic acid in osteoclastogenesis: roles and mechanisms
    Huang Xiaolin, Liao Jian, Hong Wei, Li Fang, Cheng Yuting, Zhou Qian, Dong Qiang
    2019, 23 (17):  2716-2721.  doi: 10.3969/j.issn.2095-4344.1720
    Abstract ( 549 )   PDF (889KB) ( 197 )   Save

    BACKGROUND: Zoledronic acid has been applied to treat bone resorption, but the exact mechanism is unclear.
    OBJECTIVE: To investigate the effects and mechanisms of zoledronic acid on RANKL-induced osteoclastogenesis. 
    METHODS: The viability of mouse monocyte/macrophage cell line RAW264.7 was measured using cell counting kit-8 assay and then we analyzed the half maximal inhibitory concentration (IC50). RAW264.7 cells were induced by RANKL to differentiate into osteoclasts. The induced cells were identified by rhodamine-conjugated phalloidin and 4,6-diamino-2-phenyl indole. The stage-specific effects of zoledronic acid during osteoclastogenesis were further assessed using tartrate resistant acid phosphatase staining. Bone resorption was examined using pit formation assay. Western blot was finally used to detect the expression of IκBα, P38, JNK, and ERK at protein levels. 
    RESULTS AND CONCLUSION: The IC50 of zoledronic acid in Raw264.7 cells was 33.9 μmol/L at 48 hours, and zoledronic acid at a concentration of less than IC50 suppressed the formation of osteoclasts. In addition, the number of bone resorption pits and bone resorption area were also decreased after treatment with zoledronic acid as compared with the control group. Zoledronic acid inhibited RANKL-induced IκBα phosphorylation at the protein level. To conclude, zoledronic acid can suppress osteoclastogenesis via the regulation of the nuclear factor-κB signaling pathway.

    Figures and Tables | References | Related Articles | Metrics
    Embryonic development of C-type natriuretic peptide-pretreated mouse oocytes
    Zhang Chunqiang, Zhang Tong, Zhang Guiying, Liu Yu, Wang Shuying, Liu Gaiping, Zhang Jiaxin
    2019, 23 (17):  2722-2727.  doi: 10.3969/j.issn.2095-4344.1707
    Abstract ( 472 )   PDF (689KB) ( 118 )   Save

    BACKGROUND: C-type natriuretic peptides as physiological inhibitors can inhibit meiosis in mouse oocytes, but whether it promotes the developmental ability of the obtained embryos or not is still unclear.
    OBJECTIVE: To study the effect of C-type natriuretic peptide pretreatment on the quality of mouse embryo.
    METHODS: Mouse oocytes were pretreated with C-type natriuretic peptide for 8 hours, and then undertook in vitro maturation for 24 hours. The mature oocytes were fertilized in vitro to obtain embryos (experimental group). The embryos obtained from mouse oocytes normally cultured in vitro for 24 hours were used as the control group. The study protocol in the experimental group was approved by the Animal Experimental Ethics Committee of the Wulanchabu Medical College, with the approval No. WYZLL[2016]1601.
    RESULTS AND CONCLUSION: The average number of blastocysts in the experimental group was significantly higher than that in the control group (P < 0.05). The number of mitochondrial copies in these two groups increased gradually with the development of mouse embryo, but increased faster in the experimental group than the control group (P < 0.05). The reactive oxygen species level in the experimental group was significantly lower than that in the control group (P < 0.05), and the glutathione level of embryonic cells in the experimental group was significantly higher than that in the control group (P < 0.05). To conclude, C-type natriuretic peptide pretreatment has significantly improved the developmental capacity of mouse embryos.

    Figures and Tables | References | Related Articles | Metrics
    Low-intensity pulsed ultrasound protects against high glucose-induced injury to human umbilical vein endothelial cells
    Ye Kui
    2019, 23 (17):  2728-2733.  doi: 10.3969/j.issn.2095-4344.1679
    Abstract ( 392 )   PDF (675KB) ( 100 )   Save

    BACKGROUND: Studies have shown that human umbilical vein endothelial cells participate in vascular structural disorders and dysfunction due to a series of causes, which may become a new target for the treatment of related diseases.
    OBJECTIVE: To investigate the protective effect and mechanism of low-intensity pulsed ultrasound on the high glucose-induced injury to human umbilical vein endothelial cells. 
    METHODS: Human umbilical vein endothelial cells were randomly divided into normal control group, high glucose group and 30, 60 and 90 mW/cm2 low-intensity pulsed ultrasound groups. For the high glucose group and three low-intensity pulsed ultrasound groups, the high-glucose stimulation with 25 mmol/L glucose was given. Additionally, the cells in the three low-intensity pulsed ultrasound groups received 30, 60, and 90 mW/cm2 low-intensity pulsed ultrasounds, 20 minutes per day for 7 continuous days, respectively. MTT was used to detect cell activity and flow cytometry was used to detect cell apoptosis in each experimental group. Colorimetry was used to detect Caspase-3 and -9 activities in the human umbilical vein endothelial cells. Spectrophotometry was used to detect malonaldehyde content, superoxide dismutase activity, catalase activity, and glutathione peroxidase activity. Expression of JNK in the cells was observed by western blot and RT-PCR.
    RESULTS AND CONCLUSION: After high glucose treatment, the viability of human umbilical vein endothelial cells was significantly lowered; the apoptosis rate, malonaldehyde content and activities of Caspase 3 and 9 were significantly increased (P < 0.01); the activities of superoxide dismutase, catalase and glutathione peroxidase significantly decreased (P < 0.01); and the JNK expression level was up-regulated (P < 0.01). Compared with the high glucose group, the cell viability of the low-intensity pulsed ultrasound groups (30, 60,90 mW/cm2 subgroups) was increased (P < 0.01), and the apoptosis rate, malonaldehyde content, and Caspase 3, 9 activities were decreased (P < 0.01), superoxide dismutase, catalase and glutathione peroxidase activities were increased (P < 0.01), and JNK expression level was down-regulated (P < 0.01). The above changes were most obvious when the irradiation intensity was 90 mW/cm2. In conclusion, low-intensity pulsed ultrasound can inhibit the high glucose-induced apoptosis of human umbilical vein endothelial cells by increasing the antioxidant capacity and regulating the JNK signaling pathway, further inhibiting the high glucose-induced injury to the human umbilical vein endothelial cells. The low-intensity pulsed ultrasound at 90 mW/cm2 can achieve the best outcomes.

    Figures and Tables | References | Related Articles | Metrics
    Removal of fatty acid-binding protein 4 positive stem cells affects the proliferation and self-renewal capability of clara cells in the lung
    Yang Ruichen, Liu Shuyue, Liu Huijuan
    2019, 23 (17):  2734-2738.  doi: 10.3969/j.issn.2095-4344.1702
    Abstract ( 388 )   PDF (736KB) ( 140 )   Save

    BACKGROUND: In recent years, there have been many studies about fatty acid-binding protein 4 (FABP4); however, few studies focus on the expression and function of FABP4 in the lung.
    OBJECTIVE: To systematically explore the expression and function of FABP4 in the lung.
    METHODS: FABP4 Cre; Rosa26-tdTomato mice were selected to trace red fluorescent protein expression and immunofluorescence co-localization analysis was used to systematically detect the expression of FABP4 in the lung. We made a further study on function of FABP4 in lung by constructing FABP4 Cre; iDTR transgenic mice injected with diphtheria toxin to remove the FABP4+ cells from the lung.
    RESULTS AND CONCLUSION: FABP4 could label macrophages, clara cells, type II alveolar cells, PDGFRα+ and vimentin+ mesenchymal cells in the lung of adult mice, and could not label smooth muscle cells and ciliated cells. In addition, percentages of clara cells and ciliated cells decreased when the FABP4+ cells were removed from the lung. We supposed that removal of FABP4+ cells with stem cell characteristics could influence the proliferation and self-renewal of clara cells in the lung. This study comprehensively revealed the expression pattern of FABP4 in lung of mice and preliminarily explored the FABP4 function in the lung, laying a foundation for the study of pulmonary immune response and homeostasis maintenance. Moreover, FABP4 may become a potential target for the treatment of lung diseases.

    Figures and Tables | References | Related Articles | Metrics
    Transplantation of allogeneic adipose-derived mesenchymal stem cells promotes the recovery of skeletal muscle function
    He Li, Zheng Xiaoli
    2019, 23 (17):  2739-2745.  doi: 10.3969/j.issn.2095-4344.1722
    Abstract ( 302 )   PDF (961KB) ( 111 )   Save

    BACKGROUND: An extensive damage beyond the ability of skeletal muscle to regenerate itself can lead to irreversible fibrosis, scarring and dysfunction. Previous studies have shown that adipose-derived mesenchymal stem cells can be used for the regeneration of various muscle tissues. The effect of stem cells on functional recovery after acute skeletal muscle injury has rarely been reported. 
    OBJECTIVE: To study the effect of allogeneic adipose-derived mesenchymal stem cells transplantation on skeletal muscle regeneration and functional recovery in rats with acute skeletal muscle injury.
    METHODS: Adipose-derived mesenchymal stem cells were isolated from subcutaneous adipose tissues of 10 Sprague-Dawley rats and identified by flow cytometry for multidirectional differentiation. Seventy-two Sprague-Dawley rats were randomly divided into normal control group, model group, collagen group and adipose-derived mesenchymal stem cells transplantation group. A rat model of acute blunt injury of the gastrocnemius muscle was established in the latter three groups. Then, 1 mL of type collagen I alone or containing 1×106 adipose-derived mesenchymal stem cells was injected into the gastrocnemius muscle in the collagen and adipose-derived mesenchymal stem cells transplantation groups, respectively, and there were five injection sites per rat. Hematoxylin-eosin staining was used to observe the structure of gastrocnemius muscle and measure the cross-sectional area of gastrocnemius muscle fiber 7, 14 and 28 days after transplantation. The isometric contraction force of gastrocnemius muscle was measured. The wet weight of gastrocnemius muscle was measured and the ratio of wet weight to body weight was calculated. The expressions of Pax7, MyoG and MyoD in gastrocnemius muscle tissue were detected by western blot assay.
    RESULTS AND CONCLUSION: Isolated rat adipose-derived mesenchymal stem cells were positive for CD29 and CD90, and negative for CD31 and CD34. These cells had the ability of adipogenesis, osteogenesis and chondrogenesis. Neonatal skeletal muscle fibers were observed in the injured site of the gastrocnemius muscles at 28 days after adipose-derived mesenchymal stem cells transplantation, and no fibrogenesis was observed in the gastrocnemius muscles of the four groups. At 28 days after transplantation, the wet weight of gastrocnemius muscle and its ratio to body weight in the adipose-derived mesenchymal stem cells transplantation group were higher than those in the model group and collagen group (P < 0.01), and the cross-sectional area of muscle fibers in the gastrocnemius muscle in adipose-derived mesenchymal stem cells transplantation group was larger than that in the model group and collagen group (P < 0.05). At 7, 14, and 28 days after transplantation, the isometric contractile muscle strength of the gastrocnemius muscle in the model group, collagen group and adipose-derived mesenchymal stem cells transplantation group were lower than that in the normal control group (P < 0.01). At 28 days after transplantation, the isometric contractile muscle strength of the gastrocnemius muscle in the adipose-derived mesenchymal stem cells transplantation group was higher than that in the model group and collagen group (P < 0.01). The expressions of Pax7 and MyoD in the gastrocnemius muscle of adipose-derived mesenchymal stem cells transplantation group were higher than those of the model group and collagen group at 14 days after transplantation (P < 0.05). The expressions of MyoD and MyoG in the gastrocnemius muscle of adipose-derived mesenchymal stem cells transplantation group was higher than that of model group and collagen group at 28 days after transplantation (P < 0.05). To conclude, adipose-derived mesenchymal stem cells transplantation for acute skeletal muscle injury can promote the regeneration of muscle fibers and functional recovery.

    Figures and Tables | References | Related Articles | Metrics
    Association of aging with pulmonary fibrosis and chronic obstructive pulmonary disease and treatment with mesenchymal stem cells
    Yang Yukun, Zhu Xiangqing, Ruan Guangping, Wang Yanying, Kan Xiaoli, Zhang Xuejuan, Yu Qianqian, Wang Mao, He Huanyu,Pan Xinghua
    2019, 23 (17):  2746-2752.  doi: 10.3969/j.issn.2095-4344.1714
    Abstract ( 346 )   PDF (878KB) ( 174 )   Save

    BACKGROUND: Aging is closely related to the occurrence and development of pulmonary fibrosis and chronic obstructive pulmonary disease, and mesenchymal stem cells may have therapeutic effects on senile pulmonary fibrosis and chronic obstructive pulmonary disease due to their characteristics.
    OBJECTIVE: To review the relationship between aging and pulmonary fibrosis and chronic obstructive pulmonary disease, as well as the therapeutic effect and mechanism of mesenchymal stem cells.
    METHODS: PubMed and CNKI database were searched for articles published from June 2005 to October 2018 on pulmonary fibrosis, the relationship between chronic obstructive pulmonary disease and aging, as well as the relationship between mesenchymal stem cells for the treatment of chronic obstructive pulmonary disease and pulmonary fibrosis. The key words in Chinese were “pulmonary fibrosis, chronic obstructive pulmonary disease, aging, mesenchymal stem cells”, and the English terms were “pulmonary fibrosis, COPD, aging, MSCs.” Obsolete and unrelated studies were excluded, and finally 64 articles were reviewed.
    RESULTS AND CONCLUSION: Length of the telomere, cell and immunosenescence, oxidative stress and many anti-aging molecules and changes in the extracellular matrix are closely related to pulmonary fibrosis and chronic obstructive pulmonary disease. Mesenchymal stem cells are pluripotent cells that have self-renewal, multilineage differentiation and secretion activity, adjust the aging molecules from oxidation stress, and reduce cell senescence and apoptosis, to treat pulmonary fibrosis associated with aging and chronic obstructive pulmonary disease.

    Figures and Tables | References | Related Articles | Metrics
    Three-dimensional culture of human pluripotent stem cells
    Qin Liying, Zhang Rui, Ren Xiaolin, Han Yu, Chen Haofei, Zhou Ping
    2019, 23 (17):  2753-2761.  doi: 10.3969/j.issn.2095-4344.1700
    Abstract ( 352 )   PDF (737KB) ( 170 )   Save

    BACKGROUND: Human pluripotent stem cells have the unique potential of long-term self-renewal and differentiation into almost all somatic cell types in vitro, and they are are promising candidates for cell treatment, regenerative medicine, drug screening, toxicology determination, disease modeling and stereo organogenesis. It is difficult using in vitro two-dimensional culture to obtain large quantities of cells, while three-dimensional culture provides a new way for large-scale expansion of human pluripotent stem cells. 
    OBJECTIVE: To review the current research progress in the three-dimensional culture of human pluripotent stem cells.
    METHODS: With the key words of “human pluripotent stem cells, three dimension culture, microcarrier, suspension culture, aggregates, hydrogel, microencapsulation, bioreactor system, pluripotency” in English and “pluripotent stem cells, three dimension culture” in Chinese, we performed a computer-based search in PubMed and CNKI databases respectively for relevant articles published from January 2005 to present. Finally, 77 eligible articles were included in result analysis.
    RESULTS AND CONCLUSION: Currently, three culture modes, aggregates, microcarriers, and hydrogels, are mainly used for the three-dimensional culture of human pluripotent stem cells in the laboratory. Compared with two-dimensional culture, three-dimensional culture can expand cells and increase cell yield more efficiently, which lays a good foundation for the clinical application of human pluripotent stem cells.

    Figures and Tables | References | Related Articles | Metrics
    Immunomodulatory effects of mesenchymal stem cells-derived exosomes
    Han Rui, Li Lin, Wang Runqing, Hou Zongliu
    2019, 23 (17):  2762-2769.  doi: 10.3969/j.issn.2095-4344.1699
    Abstract ( 430 )   PDF (777KB) ( 281 )   Save

    BACKGROUND: Mesenchymal stem cells (MSCs) show significant therapeutic effects on autoimmune diseases. MSCs-derived exosomes (MSCs-Exo) contain biological active molecules from the MSCs, which can regulate immune responses in the body. Therefore, MSCs-Exo as an alternative of MSCs has been used in the treatment of autoimmune diseases, which has become a new focus of research.
    OBJECTIVE: To summarize the effects of MSCs-Exo on immune cells and its application in the treatment of autoimmune diseases.
    METHODS: The key words of “mesenchymal stem cells, exosomes, extracellular vesicle, microvesicle, autoimmune, immunomodulatory” in Chinese and English were used to retrieve related literature from 1990 to 2018 in PubMed and CNKI databases. Finally, 79 articles were used for review.
    RESULTS AND CONCLUSION: MSCs-Exo has immunosuppressive effects on innate immunity, adaptive immunity and antigen presentation. Moreover, MSCs-Exo has good application prospects and has achieved great progress in the treatment of autoimmune diseases, such as multiple sclerosis, systemic lupus erythematosus, graft versus host disease, and type 1 diabetes mellitus.

    Figures and Tables | References | Related Articles | Metrics
    Cerebrospinal fluid promotes neuron-like differentiation of mesenchymal stem cells
    Ren Chao1, Ji Yongqiang2, Guan Lina3
    2019, 23 (17):  2770-2775.  doi: 10.3969/j.issn.2095-4344.1695
    Abstract ( 338 )   PDF (759KB) ( 63 )   Save

    BACKGROUND: Current research indicates that regulation of endogenous neural stem cells or transplantation of exogenous neural stem cells is the latest and most promising method for the treatment of neurological diseases such as dementia. The success of the differentiation of stem cells from other sources into neural stem cells has provided a new way for the source of neural stem cells. Recent studies have shown that cerebrospinal fluid cannot only nourish nerve cells, but also become an effective and suitable inducer to add new ways for the acquisition of neural stem cells.
    OBJECTIVE: To review the effects of cerebrospinal fluid on stem cells at home and abroad, in order to provide assistance for the clinical application of neural stem cells in the future.
    METHODS: “Cerebrospinal fluid, stem cells, induced differentiation, neural stem cells, stem cell transplantation therapy” were used as English keywords to search the PubMed database and the Embase database by computer. “Cerebrospinal fluid, stem cells, induced differentiation, proliferation, differentiation, neural stem cells, mesenchymal stem cells, embryonic stem cells, ginkgo biloba extract, stem cell transplantation therapy, neurodegenerative diseases” were used as Chinese keywords to search CNKI database, WanFang database, VIP database and other scientific journal databases. The search time was from December 10th, 1998 to December 10th, 2018. The effects of cerebrospinal fluid on mesenchymal stem cells, embryonic stem cells, and neural stem cells were summarized and analyzed, providing assistance for the clinical use of neural stem cells in the future.
    RESULTS AND CONCLUSION: (1) Interaction of cerebrospinal fluid and stem cells is the hope of treating nervous system diseases. (2) Cerebrospinal fluid can promote the differentiation of mesenchymal stem cells into neuron-like cells. (3) Cerebrospinal fluid can induce human embryonic stem cells to differentiate into neuron-like cells, but the proportion of different types of cells obtained is different. (4) Cerebrospinal fluid can induce the proliferation and differentiation of endogenous neural stem cells.

    Figures and Tables | References | Related Articles | Metrics
    Research progress in the roles of exosomal miRNA in leukemia
    Zhang Juanjuan, Li Ruiwei, He Jigang, Sa Yalian
    2019, 23 (17):  2776-2781.  doi: 10.3969/j.issn.2095-4344.1693
    Abstract ( 359 )   PDF (681KB) ( 124 )   Save

    BACKGROUND: Exosomes, known as vehicles for substance transporting and signaling communication, are nanosized bilayer-lipid membrane microvesicles secreted by living cell types that harbor biological constituents such as nucleic acids (DNA, mRNA and microRNA) proteins and lipids derived from host cells, which can potentially transfer their cargo through the extracellular fluid to the other cells at distance. Leukemia is a deadly hematologic malignancy. Recent studies have demonstrated that exosomal miRNAs protected from enzymatic degradation (RNase) by the lipid-bilayer membrane are associated with the invasion as well as metastasis in leukemia. 
    OBJECTIVE: To review the role of exosomal miRNA in leukemia, providing important information on exploring the molecular pathogenesis and targets for diagnosis and treatment of leukemia. 
    METHODS: PubMed and WanFang databases were retrieved for articles concerning leukemia and exosomal miRNA published from November 2003 to May 2018.The key words were “exosomes, leukemia, miRNAs” in English and Chinese, respectively. Forty-eight eligible articles were included in final analysis.
    RESULTS AND CONCLUSION: Exogenous miRNAs enhance the malignant biological behaviors such as survival, proliferation and migration of leukemia cells by acclimating the hematopoietic microenvironment. We can extend the concept of treating leukemia by interfering with the production and release of exogenous miRNAs, blocking the uptake of exogenous miRNAs by the recipient cells and interfering with their target genes. In-depth study on the role of exogenous miRNAs in leukemia is helpful to provide important information for mining diagnostic and therapeutic targets.

    Figures and Tables | References | Related Articles | Metrics
    Dental-derived mesenchymal stem cells promote periodontal tissue regeneration: possibility and prospects
    Du Shasha, Cai Zhiguo, Yang Kun, Liu Qi
    2019, 23 (17):  2782-2788.  doi: 10.3969/j.issn.2095-4344.1730
    Abstract ( 456 )   PDF (1432KB) ( 231 )   Save

    BACKGROUND: In recent years, dental-derived mesenchymal stem cells have made breakthroughs in the periodontal tissue regeneration of a periodontitis model, and they are the seed cells of periodontal tissue regeneration, which is also the hotspot study of periodontal tissue reconstruction 
    OBJECTIVE: To review the research progress in the use of dental-derived mesenchymal stem cells in periodontal tissue regeneration, and to propose the potential mechanism by which dental-derived mesenchymal stem cells promote periodontal tissue regeneration.
    METHODS: The related literatures addressing dental-derived mesenchymal stem cells and periodontal tissue regeneration published from 1995 to 2018 were retrieved in the databases of CNKI and PubMed. The keywords were “periodontitis, odontogenic mesenchymal stem cells/dental-derived mesenchymal stem cells, periodontal tissue regeneration, multidirectional differentiation, proliferation, self-renewal, migration, homing, immune regulation, aging, repair of periodontal tissue” in Chinese and English, respectively. Sixty-one articles were finally reviewed to analyze the characteristics and potential mechanisms of dental-derived mesenchymal stem cells for periodontal repair.
    RESULTS AND CONCLUSION: Dental-derived mesenchymal stem cells that are implanted into an animal model of periodontitis or a cell model can differentiate into periodontal tissue. Dental-derived mesenchymal stem cells are a new treatment method for the reconstruction of periodontal tissue. However, its application in periodontal tissue regeneration is still in its infancy, and several challenges, such as stem cell proliferation, differentiation, migration and homing, aging and adaptation of new organisms to the function of the body, need to be overcome.

    Figures and Tables | References | Related Articles | Metrics