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    28 July 2018, Volume 22 Issue 21 Previous Issue    Next Issue
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    Interventions for severe craniocerebral injury by nasal administration of nerve growth factor combined with bone marrow stem cell mobilization
    Wang Jun-yi, Bu Xing-yao, Gu Jian-jun, Hu Sen, Wang Bang-qing, Gao Yu-shuai
    2018, 22 (21):  3281-3285.  doi: 10.3969/j.issn.2095-4344.0895
    Abstract ( 376 )   PDF (584KB) ( 247 )   Save

    BACKGROUND: Nasal administration is a new route of administration in which drugs can bypass the blood-brain barrier and act directly on the central nervous system. It not only has good brain targeting but also has the advantages of being non-invasive and convenient. Studies have shown that nerve growth factor (NGF) combined with bone marrow stem cell (BMSC) mobilization has a synergistic effect on brain injury.
    OBJECTIVE: To observe the therapeutic effect of NGF combined with autologous BMSC mobilization via nasal administration and comprehensive rehabilitation for severe craniocerebral injury.
    METHODS: Seventy-eight patients with traumatic brain injury from the Department of Neurosurgery of Henan Provincial People’s Hospital were selected and treated with NGF intramuscular injection (once a day, for continuous 28 days) combined with BMSC mobilization and comprehensive rehabilitation therapy as control group (n=39) or treated with NGF through the nasal administration (once a day, for continuous 28 days) combined with BMSC and comprehensive rehabilitation treatment as observation group (n=39). Therapeutic schedule for autologous BMSC mobilization was as follows: subcutaneous injection of recombinant human granulocyte colony-stimulating factor or recombinant human macrophage colony-stimulating factor alternately at 1 week after brain injury, once every 3 days, and oral administration of simvastatin tablets, 10 mg per day, for continuous 28 days. Two groups of patients continued to be treated with NGF for 3 months after discharge.
    RESULTS AND CONCLUSION: At 28 days after treatment, the neurologic defect score in the observational group was slightly lower than that in the control group, but there was no significant difference between the two groups (t=0.429, P > 0.05). At 3 months after treatment, the score on the National Institutes of Health Stroke Scale was significantly better in the observational group than the control group (t=7.176, P < 0.05), and the score on the Glasgow Coma Scale Glasgow was also significantly higher in the observational group than the control group (P < 0.05). No obvious adverse event occurred in the two groups during the treatment and follow-up. To conclude, nasal administration of NGF combined with autologous BMSC mobilization and rehabilitation therapy can effectively promote the repair of severe craniocerebral injury and significantly improve the neurological function of the patients.

    中国组织工程研究杂志出版内容重点:干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程

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    Drug-loaded tumor exosomes combined with radiotherapy inhibit the proliferation of breast cancer stem cells
    Luo Qiong, Gao Guo-xiang, Qin Shi-yun
    2018, 22 (21):  3286-3291.  doi: 10.3969/j.issn.2095-4344.0502
    Abstract ( 370 )   PDF (641KB) ( 253 )   Save

    BACKGROUND: In recent years, studies have found that drug-loaded tumor exosomes have a high affinity with tumor cells from corresponding origins, but have a low binding force to other cells, thus becoming an efficient targeted drug carrier.
    OBJECTIVE: To observe the effect of drug-loaded tumor exosomes combined with radiotherapy on the proliferation of breast cancer stem cells.
    METHODS: Tumor exosomes were isolated from ZR-75-30 human breast ductal carcinoma cells by ultracentrifugation and used to wrap methotrexate and prepare drug-loaded tumor exosomes. CD133+ ZR-75-30 was isolated from human breast cancer cells in breast cancer stem cells by flow cytometry. The CD133+ cells were cultured in routine medium as blank control group, in RPMI 1640 medium containing drug-loaded tumor exosomes for 24 hours as exosome group, and in RPMI 1640 medium containing drug-loaded tumor exosomes for 24 hours followed by 2, 4, 6 Gy X-ray irradiation as low-, middle- and high-dose groups. After 7 days of culture, tumor spheres formed under inverted microscope, and sphere number and volume were recorded. Expression of Nanog, Sox-2, and Oct-4 was detected by western blot assay.
    RESULTS AND CONCLUSION: Compared with the blank control group, the tumor exosome group had significantly decreased number and size of tumor spheres (P < 0.05); compared with the tumor exosome group, low-, middle- and high-dose radiotherapy groups had significantly decreased number and size of tumor spheres (P < 0.05), and the reduction was increased with the increasing of radiation dose. Compared with the blank control group, lower expression of Nanog, Sox-2, and Oct-4 was found in the tumor exosome group (P < 0.05); compared with the tumor exosome group, there was also a significant reduction in the expression of Nanog Sox-2, Oct-4 in the three radiotherapy groups (P < 0.05), and the reduction was increased with the increasing of radiation dose. To conclude, the combined use of radiotherapy and drug-loaded tumor exosomes inhibits the proliferation activity of CD133+ breast cancer stem cells in a radiation dose-dependent manner.

    中国组织工程研究杂志出版内容重点:干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程

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    A molecular study on myocardial repair via exosomes secreted from GATA-4-overexpressed bone marrow mesenchymal stem cells
    He Ji-gang, Han Jin-xiu, Yan Dan, Li Bei-bei, Sa Ya-lian, Xie Qiao-li
    2018, 22 (21):  3292-3298.  doi: 10.3969/j.issn.2095-4344.0528
    Abstract ( 327 )   PDF (778KB) ( 198 )   Save

    BACKGROUND: GATA-4 is a zinc finger transcription factor that is specifically associated with cardiac development. Previous experiments have found that exosomes secreted from GATA-4-overexpressed bone marrow mesenchymal stem cells (BMSCs) co-cultured with BMSCs can make BMSCs express more myocardial-specific antigens. When co-cultured with myocardial cells in a hypoxic environment, these exosomes can inhibit apoptosis in myocardial cells.
    OBJECTIVE: To identify from a molecular level the basic and essential exosomes secreted from GATA-4-overexpressed mouse BMSCs that has a significant role in cardiac repair after myocardial infarction.
    METHODS: (1) GATA-4-overexpressed mouse BMSCs were constructed by transfecting mouse BMSCs with GV308 (a lentiviral vector)-carrying GATA-4 before adding doxycycline for gene induction. ExoQuick-TC (SBI Inc.) was then used to extract the secreted exosomes. (2) The BMSCs were co-cultured with GATA-4-BMSCs-Exosome, free-vector-BMSCs-Exosomes, and BMSCs-Exosome. Another BMSCs and mouse myocardial cells were cultured alone. The expression levels of myocardial specific antigens, cTnT, α-actin, connexin 43, and Desmin, were assessed via qPCR quantification at 24 hours of culture. (3) The mouse myocardial cells were then co-cultured with GATA-4-BMSCs-Exosome, free-vector-BMSCs-Exosomes, and BMSCs-Exosome, and were subsequently mono-cultured in hypoxia and in serum-free cultures to construct the apoptosis-positive control group. Normally cultured myocardial cells were as negative controls. Cell apoptosis rates in different groups were determined by flow cytometry. (4) The microRNAs, which were associated with cellular differentiation or anti-apoptosis, in the exosomes secreted from GATA-4-overexpressed mouse BMSCs were detected by Agilent microRNA microarray.
    RESULTS AND CONCLUSION: Results from Q-PCR and flow cytometry suggested that the exosomes secreted from GATA-4-overexpressed mouse MBSCs effectively facilitated the differentiation of BMSCs to form myocardial cells and reduce apoptosis. The Agilent microRNA microarray test results showed that the key microRNAs associated with differentiation included mmu-miR-199a-3p (up-regulated) and mmu-miR-1894-5p (down-regulated), while the key microRNAs associated with the anti-apoptotic function included mmu-miR-199a-3p, mmu-miR-20a-5p, and mmu-miR-330-3p, all of which were up-regulated. Among these microRNAs, mmu-miR-199a-3p was the only one associated with both cellular differentiation and anti-apoptosis, and it was therefore considered as the most primary microRNA to be validated. 

    中国组织工程研究杂志出版内容重点:干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程

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    17Beta-estradiol combined with icariin promotes the osteogenic differentiation of bone marrow mesenchymal stem cells from Sprague-Dawley rats
    Yang Yan-bing, Jin Xian-hui, Wang Hai-ping
    2018, 22 (21):  3299-3303.  doi: 10.3969/j.issn.2095-4344.0879
    Abstract ( 247 )   PDF (723KB) ( 237 )   Save

    BACKGROUND: Previous studies have shown that 17β-estradiol and icariin can both promote the osteogenic differentiation of rat bone marrow mesenchymal stem cells (BMSCs), but their combined use is rarely reported.
    OBJECTIVE: To observe the effects of 17β-estradiol combined with icariin on the proliferation and osteogenic differentiation of BMSCs.
    METHODS: BMSCs were isolated and cultured by whole-bone marrow adherence separation. Surface markers (CD29, CD45, CD90) of BMSCs were identified by flow cytometry. Cultured cells were divided into control group, 17β-estradiol group, icariin group, combined induction group, followed by corresponding treatments. At 7, 14 and 21 days after osteogenic induction, alkaline phosphatase activity, levels of collagen type I and osteocalcin were detected, and alizarin red staining was performed to observe the formation of calcium nodules.
    RESULTS AND CONCLUSION: The osteogenic ability of BMSCs treated with 17β-estradiol combined with icariin was enhanced. After 7 days of osteogenic induction, the alkaline phosphatase activity was detected in all groups, and ranked as follows: combined induction group > 17β-estradiol group > icariin group > control group. After 14 days of osteogenic induction, the expression of collagen type I was observed in all groups and ranked as follows: combined induction group > 17β-estradiol group=icariin group > control group. After 21 days of osteogenic induction, osteocalcin was expressed in all groups and ranked as follows: induction group > 17β-estradiol group > icariin group > control group. The number of calcium nodules as determined by alizarin red staining was ranked as follows: induction group > 17β-estradiol group=icariin group > control group. Therefore, 17β-estradiol and Icariin have synergistic effects to induce BMSCs to differentiate into bone cells.

    中国组织工程研究杂志出版内容重点:干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程

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    In vivo ectopic osteogenesis of adipose-derived mesenchymal stem cells/osteoblasts combined with hydroxyapatite/chitosan/polylactic acid
    Tian Xue-tao, Wang Xian-xun, Wang Xiao-wei
    2018, 22 (21):  3304-3309.  doi: 10.3969/j.issn.2095-4344.0522
    Abstract ( 249 )   PDF (891KB) ( 275 )   Save

    BACKGROUND: Osteoblast deficiency is a key problem in bone tissue engineering, and transplantation of mesenchymal stem cells combined with osteoblast can achieve ideal results.
    OBJECTIVE: To investigate the in vivo ectopic osteogenesis of adipose-derived mesenchymal stem cells (ADSCs) and osteoblasts (OB) combined with hydroxyapatite (HA)/chitosan (CS)/poly(L-latic acid) (PLLA).
    METHODS: ADSCs and OB were obtained by adherent method and enzymatic digestion method. ADSCs, OB and the mixture of ADSCs and OB (at a mixture ratio of 1:1) were cultured with HA/CS/PLLA, respectively. After 48 hours of in vitro culture, cell-scaffold complexes were subcutaneously implanted into the back of Sprague-Dawley rats in corresponding groups, and HA/CS/PLLA without cells was implanted as control group. The rats in each group were killed at 8 weeks postoperatively. The macroscopic and histopathological observations were performed to assess the ectopic osteogenesis potential.
    RESULTS AND CONCLUSION: (1) After adipogenic, chondrogenic and osteogenic induction, ADSCs were positive for oil red O, toluidine blue and alizarin red staining. Results from flow cytometry showed that ADSCs were positive for CD147, CD90, CD105 and CD44 with the rate of positivity > 80%, but negative for CD117, CD34, CD131, CD45 with the rate of positivity < 5%. (2) Passage 3 OB were positive for both alizarin red staining and alkaline phosphatase staining. (3) At 8 weeks after implantation, soft tissues grew into the complexes under gross observation. (4) At 8 weeks after implantation, ectopic bone formation was visible in each group. The bone formation was more visible in the ADSCs-OB/HA/CS/PLLA group than the other groups with significant differences (P < 0.05). To conclude, ADSCs can promote the ectopic bone formation of OB in vivo in combination with HA/CS/PLLA scaffold.

    中国组织工程研究杂志出版内容重点:干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程

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    Regulation of Smad4 by miRNA-196a-5p influences gastric cancer stem cell characteristics
    Guo Rui, Dai Jian-feng, Luo Yu-ming, Zhao Hai-ming, Tang Peng
    2018, 22 (21):  3310-3315.  doi: 10.3969/j.issn.2095-4344.0907
    Abstract ( 333 )   PDF (683KB) ( 254 )   Save

    BACKGROUND: miRNA-196a is a recently discovered microRNAs biotarget molecule associated with various tumors such as breast cancer and cervical cancer. Studies have confirmed that miRNA-196a-5p is upregulated in both gastric cancer cell line and gastric cancer tissues. However, little is known about the function and mechanism of miRNA-196a-5p in gastric cancer stem cells.
    OBJECTIVE: To analyze the function of miRNA-196a-5p in the invasion of gastric cancer stem cells and to investigate the possible mechanism.
    METHODS: CD44+ gastric cancer stem cells were sorted from the gastric cancer BGC-823 cell line using flow cytometry. The expression of miRNA-196a-5p was detected by quantitative real-time PCR (qRT-PCR) and the cell invasion was determined by Transwell assay. With reference to the specification of Lipofectamine 2000m kit, miRNA-196a-5p inhibitor (miRNA-196a-5p INH) was transferred into the sorted cells. Regulation of Smad4 gene by the miRNA-196a-5p was validated by dual-luciferase reporter gene assay. Expression of epithelial-mesenchymal transition-associated proteins (E-cadherin, N-cadherin and Vimentin) and Smad4 protein was evaluated by western blot assay.
    RESULTS AND CONCLUSION: The miRNA-196a-5p was up-regulated in the gastric cancer stem cells (P < 0.05). Inhibiting the miRNA-196a-5p expression could reduce the invasion ability of gastric cancer stem cells (P < 0.05), increase the E-cadherin protein expression (P < 0.05), decrease the N-cadherin and Vimentin protein expression (P < 0.05), and enhance the Smad4 protein expression (P < 0.05). Therefore, miR-196a-5p has a key role in epithelial-mesenchymal transition and invasion by targeting Smad4 in the gastric cancer stem cells. miR-196a-5p may serve as a potential target for gastric cancer therapy.

    中国组织工程研究杂志出版内容重点:干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程

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    miR-15 family promotes the migration and invasion of CD133+ pancreatic cancer stem-like cells
    Cai Shang-dang, Cai Man-di, Lou Ning, Guo Yan-ping, Yin Tao
    2018, 22 (21):  3316-3321.  doi: 10.3969/j.issn.2095-4344.0897
    Abstract ( 293 )   PDF (937KB) ( 216 )   Save

    BACKGROUND: Some studies have shown that CD133 is a stem cell marker for a variety of tumor cells, such as pancreatic cancer, which is associated with a poor prognosis in cancer patients. miR-15 family is involved in cell apoptosis, differentiation, cycle regulation and stress, and has potential value as an intervention.
    OBJECTIVE: To investigate the effects of miR-15 family on the migration and invasion of CD133+ pancreatic cancer stem-like cells.
    METHODS: First, a highly migrating pancreatic cancer cell line, Capan-1M9, was constructed, and then CD133+Capan-1M9 cell lines that overexpressed miR-15a, miR-15b and miR-15c were constructed by lentivirus transduction. NC-miRNA cell lines were taken as negative controls. Expression of miR-15a, miR-15b and miR-15c in the recombinant cell lines and epithelial-mesenchymal transition (EMT)-related proteins, fibronectin, vimentin and N-cadherin mRNA were determined by qRT-PCR. MTT assay was used to detect the proliferation and gemcitabine resistance of recombinant cell lines. Spheroid formation test was used to detect the self-renewal ability of recombinant cell lines. Migration and invasion ability of the recombinant cell lines were detected by cell migration and invasion assay. EMT-related proteins fibronectin, vimentin and N-cadherin were detected by western blot.
    RESULTS AND CONCLUSION: qPCR results showed that the expression of miR-15a, miR-15b and miR-15c in the CD133+ Capan-1M9 cell lines increased by 8.3, 10 and 9.5 times compared with the negative control group, and the expression of fibronectin, vimentin and N-cadherin mRNA was also significantly increased (P < 0.05). There was no significant difference in cell proliferation between the recombinant cell lines and the negative control group (P > 0.05), but the gemcitabine resistance was significantly increased in the recombinant cell lines as detected by the MTT (P < 0.05). The number and volume of spheres in the recombinant cell lines did not change significantly compared with the negative control group (P > 0.05). The cell migration and invasion abilities of the recombinant cell line were significantly enhanced compared with the negative control group (P < 0.05). Our experimental findings suggest that the miR-15 family can promote migration and invasion of CD133+ pancreatic cancer stem-like cells via EMT regulation.

    中国组织工程研究杂志出版内容重点:干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程

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    Paracrine abilities of adipose-derived mesenchymal stem cells and umbilical cord mesenchymal stem cells under different oxygen concentrations
    Yang Ji-nong, Jiang Yi-yao, Yuan Chao, Liu Zhi-gang, Liu Xiao-cheng
    2018, 22 (21):  3322-3327.  doi: 10.3969/j.issn.2095-4344.0880
    Abstract ( 353 )   PDF (707KB) ( 287 )   Save

    BACKGROUND: Therapeutic mechanisms of mesenchymal stem cells for acute myocardial infarction are related to the migration, colonization, and differentiation of mesenchymal stem cells, and more importantly, it is related to the paracrine effects of mesenchymal stem cells.
    OBJECTIVE: To evaluate the paracrine and vascular regeneration abilities of human adipose-derived mesenchymal stem cells (hAD-MSCs) and human umbilical cord mesenchymal stem cells (hUC-MSCs) under low oxygen concentrations, thereby providing the basis for the selection of appropriate mesenchymal stem cells used in the treatment of acute myocardial infarction.
    METHODS: hUC-MSCs and hAD-MSCs were isolated and cultured, and cell immunophenotype was identified using flow cytometry. Two kinds of cells were pretreated with 3%, 5% and 21% (control) O2 for 24 hours. Enzyme linked immunosorbent assay was used to detect the contents of hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF), nerve growth factor (NGF) and keratinocyte growth factor (KGF) in the cell supernatant in each group.
    RESULTS AND CONCLUSION: hUC-MSCs and hAD-MSCs were positive for CD73, CD90 and CD105, and negative for CD34, CD45, CD54 and HLA-DR. Under different oxygen concentrations, the VEGF level in the hAD-MSCs was significantly higher than that in the hUC-MSCs  (P < 0.01). Under 3% O2 conditions, the HGF level in the hAD-MSCs was significantly higher than that in the hUC-MSCs (P < 0.05). Under 3% and 5% O2, the NGF level in the hUC-MSCs was significantly higher than that in the hAD-MSCs (P < 0.01). Under 3% and 5% O2, the KGF level in the hUC-MSCs was significantly higher than that in the hAD-MSCs (P < 0.01 or P < 0.05). Under 21% O2, the KGF level in the hAD-MSCs was significantly higher than that in the hUC-MSCs (P < 0.01). To conclude, hypoxia can promote the paracrine effects of and hAD-MSCs. Moreover, hUC-MSCs show better paracrine ability than hAD-MSCs. Therefore, hAD-MSCs are more likely to be a stem cell therapy suitable for myocardial infarction.

    中国组织工程研究杂志出版内容重点:干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程

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    Mechanism by which UM171 sustains expansion of umbilical cord blood hematopoietic stem cells in vitro
    Xu Shi-qi, Ding Ya-hui, Zhang Yu, Ji Qing, Yang Ming, Li Ying-hui, Gao Ying-dai
    2018, 22 (21):  3328-3334.  doi: 10.3969/j.issn.2095-4344.0898
    Abstract ( 473 )   PDF (903KB) ( 277 )   Save

    BACKGROUND: It has been reported that UM171 enables an ex vivo expansion of human hematopoietic stem cells. However, the intracellular regulatory mechanisms remain unclear.
    OBJECTIVE: To investigate the compound-target interaction network of UM171 by High-Throughput Docking (HTDocking) screening technology and TargetHunter, and to outline its potential mechanisms of action.
    METHODS: Using the online StemCellCKB interface, we searched the possible targets of UM171. Negative targets were excluded by validation experiments, and a surface plasmon resonance (SPR) assay was used to identify the interaction between UM171 and transforming growth factor βRI. Several important proteins which are known to regulate this pathway were investigated by western blot. 
    RESULTS AND CONCLUSION: StemCellCKB program automatically calculated the docking scores, which indicated the possible targets of UM171. The KD50 values were calculated as 62.5 µmol/L by SPR, indicating the high affinity between UM171 and its target protein. Western blot analysis results revealed that the expression levels of main proteins in transforming growth factor β signaling pathway, including TGF-βRI, Smad3, p-Smad3, Smad4, were increased significantly in a concentration-depend manner. Overall, UM171 can sustain the expansion of umbilical cord blood hematopoietic stem cells through the transforming growth factor β signaling pathway.

    中国组织工程研究杂志出版内容重点:干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程

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    YAP effect on C6 glioma stem cell properities
    Ma Yi-ming, Xia Xiang-guo
    2018, 22 (21):  3335-3340.  doi: 10.3969/j.issn.2095-4344.0523
    Abstract ( 313 )   PDF (766KB) ( 206 )   Save

    BACKGROUND: YAP protein can promote the activation of stem cell-associated proteins. Therefore, it is speculated that YAP plays an important role in maintaining the stem cell characteristics of C6 glioma cells, but no studies have been reported in this regard.
    OBJECTIVE: To explore the function of YAP protein in the maintenance of C6 glioma stemness.
    METHODS: C6 glioma cells were cultured in serum-free medium to obtain C6 glioma stem cells, and immunofluorescence staining was used to detect CD133 and Nestin. Western blot, qRT-PCR and immunofluorescence staining were used to observe the differences of YAP expression between glioma stem cells and glioma cells. Lentiviral transfection was further used to transfect C6 glioma cells and glioma stem cells to make the cells overexpress or knock down the YAP protein. The protein levels of YAP, CD44, Nanog and Oct-4 were tested by western blot assay. The stem cell formation ability of tumor cells was determined in the cloning sphere test.
    RESULTS AND CONCLUSION: C6 glioma stem cells expressed CD133 and Nestin. The protein and mRNA levels of YAP in C6 glioma stem cells were higher than those in C6 glioma cells. Overexpression of YAP in C6 glioma cells significantly up-regulated the expression of CD44, Nanog and Oct-4, enlarged and increased the tumor spheres of tumor stem cells. Conversely, knockdown of YAP in C6 glioma stem cells obviously decreased the stem cell properties. In conclusion, tumor stem cells exist in C6 glioma cells, and YAP overexpression in the glioma stem cells is highly associated with the maintenance of stem cell properties.

    中国组织工程研究杂志出版内容重点:干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程

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    Hepatocellular carcinoma with high and low metastatic potential before and after bone marrow mesenchymal stem cell transplantation: a MRI imaging study using Gd-RGD probe
    Li Tian-ran, Huang Xiao-bin, Yang Zhi-jie, Lu Guang-ming, Li Yan-jun, Yu Ming-hui
    2018, 22 (21):  3341-3348.  doi: 10.3969/j.issn.2095-4344.0899
    Abstract ( 300 )   PDF (978KB) ( 184 )   Save

    BACKGROUND: With the advancement of modern molecular imaging, possibilities to monitor the efficacy of bone marrow mesenchymal stem cells (BMSCs) against tumors have been achieved.
    OBJECTIVE: To construct a novel metastasis-associated MRI molecular imaging probe, Gd-RGD, and to observe metastasis and proliferation of hepatocellular carcinoma (HCC) before and after intervention with BMSCs using MRI imaging
    .METHODS: The metastasis-associated MR molecular imaging probe, integrin αvβ3 ligand cRGD-PEG-DGL-DTPA-Gd (Gd-RGD), was constructed, and the ingredient analysis and identification were implemented through 1H-magnetic resonance spectroscopy (1H-MRS) and inductively coupled plasma-atomic emission spectrometry (ICP-AES) methods. MHCC97-H and MHCC97-L animal models were established. After BMSCs intervention was administrated via the tail vein for 6 weeks, tumor weight inhibition rate was calculated. MRI imaging with a metastasis-associated integrin ligand RGD molecular probe was performed. Molecular imaging probe Gd-DTPA was taken as control. Signal noise ratio (SNR) and contrast to noise ratio (CNR) of MRI were taken as semi-quantitative indicators. MHCC97-H and MHCC97-L animal models before BMSCs intervention were co-cultured with BMSCs using Transwell method. Quantitative PCR method was used to detect proliferation and metastasis-associated indicators, tumor growth factor β1 (TGF-β1), osteopontin, integrin subunits αv and β3.
    RESULTS AND CONCLUSION: (1) After BMSCs transplantation, the tumor tissue weight of HCC decreased obviously, and the tumor weight inhibition rate was peaked in the 3rd week. (2) For high metastatic potential (MHCC97-H), both SNRs and CNRs of Gd-RGD MR imaging before and after BMSCs intervention were statistically different (P < 0.05). For low metastatic potential (MHCC97-L), SNRs of Gd-RGD MR imaging before and after BMSCs intervention were not statistically different (P > 0.05), while CNRs were statistically different (P < 0.05). (3) SNRs of Gd-RGD MRI were significant different between MHCC97-L and MHCC97-H after transplantation (P < 0.05), while SNRs and CNR of Gd-RGD MRI changed significantly as compared with those of Gd-DTPA after cell transplantation. (4) In MHCC97-H cells co-cultured with BMSCs, the osteopontin, integrin subunits αv and β3 and TGF-β1 expression significantly decreased (P < 0.05), but integrin subunit αv expression did not change obviously (P > 0.05). In MHCC97-L cells co-cultured with BMSCs, OPN, β3, TGFβ1 and αv expression significantly decreased (P < 0.05). These findings reveal that the CNR index of MR imaging in two kinds of tracers is a good indicator to distinguish high and low potential HCC tissues. After BMSCs transplantation, the SNR and CNR indexes of Gd-DTPA and Gd-RGD can both distinguish high and low potential HCC tissues, and Gd-RGD imaging can achieve a more accurate distinction compared with Gd-DTPA.

    中国组织工程研究杂志出版内容重点:干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程

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    Transplantation of neural stem cells from different sources in the treatment of cerebral ischemia injury in rats
    Zhong Bo, Liu Xia, Wu Wei
    2018, 22 (21):  3349-3356.  doi: 10.3969/j.issn.2095-4344.0881
    Abstract ( 250 )   PDF (869KB) ( 281 )   Save

    BACKGROUND: The underlying mechanism of neurological dysfunction caused by cerebral ischemia is neuronal damage, and facilitating neuronal regeneration is the key to neural function recovery. However, endogenous neural stem cells have limited use in nerve repair. Transplantation of exogenous neural stem cells brings hope for tissue remodeling and functional recovery after cerebral ischemia, but systematic comparative studies on the selection of seed cells are still lacking.
    OBJECTIVE: To compare the therapeutic effect of neural stem cells from three sources in the treatment of cerebral ischemia injury in rats.
    METHODS: Adipose-derived mesenchymal stem cells (ADMSCs), bone marrow mesenchymal stem cells (BMSCs), and skin-derived induced pluripotent stem cells (iPSCs) from Sprague-Dawley rats were isolated and cultured, and induced in vitro to differentiate into neural stem cells. Conversion efficiency was detected at 7 days of neuronal induction. One hundred rat models of cerebral ischemia were randomized into model, BMSCs, iPSCs, ADMSCs, and PBS groups, with 20 rats in each group. Then, corresponding cell suspension or PBS solution was transplanted in each group. Another 40 Sprague-Dawley rats were taken as sham operation group (n=20) and control group (n=20) with no intervention. Index measurements were performed at 1 and 4 weeks after cell transplantation.
    RESULTS AND CONCLUSION: After 7 days of in vitro induction, the conversion efficiency of iPSCs was significantly higher than that of ADMSCs and BMSCs (P < 0.01). At 1 and 4 weeks after transplantation, neuronal apoptosis and infarction size were significantly reduced in the iPSCs, ADMSCs and BMSCs groups as compared with the PBS and model groups (P < 0.05). Moreover, neurological severity score, infarction size and neuronal apoptosis were significantly reduced in the iPSCs group as compared with the ADMSCs and BMSCs groups (P < 0.05). At 4 weeks after cell transplantation, neurological severity score, infarction size and neuronal apoptosis in each group showed significant reduction as compared with the values at 1 week after cell transplantation (P < 0.01). Numbers of Nissl bodies in neurons of the striatum in the three cell transplantation groups were significantly higher than those in the control and sham operation groups. Our findings from this study reveal that neural stem cells differentiated from three sources can significantly improve the symptoms of neurological deficits, and reduce infarction size, neuronal degeneration and neuronal apoptosis. iPSCs especially have better differentiation ability and therapeutic effects than BMSCs and ADMSCs.

    中国组织工程研究杂志出版内容重点:干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程

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    Sorting human skeletal muscle-derived myoendothelial cells and perivascular stem cells by multiparameter fluorescence-activated cell sorting
    Gu Jing-jing, Yang Ji-hui, Yang Ting-ting, Yang Xiao-ping, Zheng Bo
    2018, 22 (21):  3357-3364.  doi: 10.3969/j.issn.2095-4344.0900
    Abstract ( 400 )   PDF (1022KB) ( 310 )   Save

    BACKGROUND: At present, the preplate method is widely used for the separation of skeletal muscle-derived stem/progenitor cells. However, little is reported on the sorting of human skeletal muscle-derived stem/progenitor cells using multiparameter fluorescence-activated cell sorting (MP-FACS).
    OBJECTIVE: To explore the method of sorting high-purity myoendothelial cells and perivascular stem cells from human skeletal muscle tissues by MP-FACS.
    METHODS: Human skeletal muscle tissue was collected and digested with collagenase (type I and type IV) and dispase, to collect mononuclear cells. Myoendothelial cells with phenotype (CD56+CD34+CD144+CD45-) and perivascular stem cells with phenotype (CD146+CD45-CD34-CD144-CD56-) were sorted by MP-FACS.
    RESULTS AND CONCLUSION: Fourteen samples of MECs and PSCs were sorted by MP-FACS. Myoendothelial cells and perivascular stem cells accounted for (0.04±0.01)% and (0.30±0.07)% in human skeletal muscle mononuclear cells, respectively. After the freshly sorted cells were re-analyzed by flow cytometry, the purity of myoendothelial cells and perivascular stem cells was up to (96.80±1.16)% and (92.50±0.50)%, respectively, and the survival rate of myoendothelial cells and perivascular stem cells reached (95.58±1.10)% and (95.15±0.67)%, respectively. After primary culture, myoendothelial cells and perivascular stem cells grew well, and furthermore, they could be successfully induced to differentiate into osteoblasts and adipocytes in vitro, respectively, indicating that myoendothelial cells and perivascular stem cells have good multi-differentiation ability. To conclude, the myoendothelial cells and perivascular stem cells obtained by MP-FACS have high purity and good activity.

    中国组织工程研究杂志出版内容重点:干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程

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    Intervention with pyrrolidine dithioearbamate stimulates expression of RANKL and OPG in lipopolysaccharide-stimulated periodontal ligament stem cells
    Wang Ping-ting, Zhou Pan, Zheng Guo-ying, Liu Da-yong
    2018, 22 (21):  3365-3370.  doi: 10.3969/j.issn.2095-4344.0901
    Abstract ( 268 )   PDF (719KB) ( 251 )   Save

    BACKGROUND: It is generally believed that various cytokines, such as receptor activator of nuclear factor-κB ligand (RANKL) and osteoprotegerin (OPG), which regulate osteoclast and osteoblast formation and differentiation, are mainly secreted by osteoblasts and bone marrow stromal cells. Whereas in the periodontal tissues, homologous periodontal ligament stem cells (PDLSCs) also play a significant role in the regulation of inflammation and immunity. Thus, virulence factors are very likely to mediate alveolar bone resorption by involvement in the regulation of RANKL and OPG.
    OBJECTIVE: To explore whether the inhibition of nuclear factor-κB activity by pyrrolidine dithiocarbamate (PDTC) can relieve the imbalance of RANKL/RANK/OPG system in PDLSCs in inflammatory state.
    METHODS: After isolation, culture and differentiation in vitro, passage 4 PDLSCs were divided into four group: control group, cultured in the DMEM medium containing 10% fetal bovine serum; lipopolysaccharide (LPS) group, cultured in the DMEM medium containing 10 mg/L LPS; 10 μmol/L PDTC group, pretreated with 10 μmol/L PDTC for 30 minutes followed by removal of the medium and addition of the medium containing 10 mg/L LPS; 100 μmol/L PDTC group, pretreated with 100 μmol/L PDTC for 30 minutes followed by removal of the medium and addition of the medium containing 10 mg/L LPS. In the latter two groups, cell morphology was observed under inverted microscope at 30 minutes after PDTC pretreatment. After 24 hours of culture, expression of OPG and RANKL mRNA and the ratio of RANKL/OPG in cells were detected in each group.
    RESULTS AND CONCLUSION: (1) PDTC pretreatment at a concentration of 100 μmol/L could cause cell morphological changes: some cells were adherent and retracted, and became round with the cell body shrinking in size. (2) Compared with the control group, the expression of RANKL in the PDLSCs was significantly increased in the LPS group (P < 0.05), and the expression of RANKL in the PDLSCs pretreated with 10 μmol/L PDTC had no significant change (P > 0.05), while compared with the LPS group, the expression of RANKL in the PDLSCs pretreated with 100 μmol/L PDTC was significantly lowered (P < 0.05). (3) Compared with the control group, the expression of OPG in the PDLSCs was slightly lowered in the LPS group (P > 0.05). After pretreatment with 10 μmol/L PDTC, the expression of OPG in the PDLSCs was significantly increased (P <0.05) compared with the LPS group, while the expression of OPG in the PDLSCs pretreated with 100 μmol/L PDTC had no significant difference from that in the LPS group (P > 0.05). (4) Compared with the control group, the ratios of RANKL/OPG in the other groups were significantly increased (P < 0.05), especially in the LPS group. With the increase of PDTC concentration, the ratio of RANKL/OPG decreased gradually(P < 0.05). These results reveal that PDTC can relieve the imbalance of RANK/RANKL/OPG system in the PDLSC in inflammatory state by inhibiting nuclear factor-κB activity.

    中国组织工程研究杂志出版内容重点:干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程

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    Fibroblasts-derived induced pluripotent stem cells in pulp revascularization: differentiation into vascular endothelial cells and co-culture with dental pulp stem cells
    Lü Ji-zhong
    2018, 22 (21):  3371-3375.  doi: 10.3969/j.issn.2095-4344.0902
    Abstract ( 370 )   PDF (616KB) ( 186 )   Save

    BACKGROUND: Dental pulp vascularization is an important process to provide nutrients and energy for the dental pulp regeneration. The choice of stem cells and their directional differentiation into vascular endothelial cells have become an important issue of research in the pulp regeneration. 
    OBJECTIVE: To investigate the feasibility of mouse fibroblasts-derived induced pluripotent stem cells differentiating into vascular endothelial cells and forming new blood vessels by co-culture with dental pulp stem cells.
    METHODS: (1) The feeder layer of mouse Sertoli cells was prepared by enzyme digestion. (2) Mouse fibroblasts-derived induced pluripotent stem cells were induced by vascular endothelial growth factor and basic fibroblast growth factor to differentiate into vascular endothelial cells, and differentiated cells were then identified. (3) The co-culture system of vascular endothelial cells and dental pulp stem cells was established. Real-time fluorescence quantitative real-time PCR was used to detect mRNA expression of CD34 and vascular endothelial growth factor in the two groups.
    RESULTS AND CONCLUSION: After 14 days of induced differentiation, the morphology of the vascular endothelium was visible under the inverted microscope. Flow cytometry results showed the differentiated cells were positive for CD31, indicating the phenotype of endothelial cells. Compared with the control group, the expression of endothelin and endothelial nitric oxide synthase increased (P < 0.01), and the expression of prostacyclin decreased in the co-culture group at 14 days of induced differentiation (P < 0.01). Compared with the control group, the expression of CD34 and vascular endothelial growth factor increased at 5 days of co-culture (P < 0.01). These findings indicate that mouse fibroblasts-derived induced pluripotent stem cells can directionally differentiate into vascular endothelial cells and form new blood vessels by co-culture with dental pulp stem cells.

    中国组织工程研究杂志出版内容重点:干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程

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    An improved method for isolation of mouse primary hepatic stellate cells with high yield and purity
    Xu Ying, Zhang Ding-qi, Mu Yong-ping, Chen Jia-mei, Wang Qing-lan, Ping Jian, Liu Wei, Liu Ping
    2018, 22 (21):  3376-3380.  doi: 10.3969/j.issn.2095-4344.0903
    Abstract ( 881 )   PDF (727KB) ( 488 )   Save

    BACKGROUND: Due to the small liver and fine blood vessels in the mice, it is difficult to isolate primary hepatic stellate cells, resulting in a limited yield which cannot meet the needs of in vitro experiments.
    OBJECTIVE: To explore the high-performance and stable method for isolation of mouse primary hepatic stellate cells, with high yield and purity, thereby laying an experimental foundation for studying the mechanism of hepatic fibrosis.
    METHODS: Adult male C57BL/6 mice undertook liver infusion with prefusion solution with no calcium and magnesium ions via the portal vein, followed by digestion using 1 g/L pronase and 0.7 g/L collagenase. Then, the liver samples were centrifuged with Nycodenz density gradient solution to obtain primary hepatic stellate cells from the middle layer. Trypan blue staining method was used to calculate cell viability, and flow cytometry method was used to measure cell purity. Immunofluorescence method was used to detect the expression of Desmin in cells. Cell morphology was observed under inverted microscope at 3, 5, 7 days of primary culture, and the expression of α-smooth muscle actin was detected by PCR.
    RESULTS AND CONCLUSION: The yield of cells per mouse was (5.5±0.4)×106 cells. Trypan blue assay showed that the viability of isolated cells was over 95%, and the purity of isolated cells was 94% as measured by the flow cytometry. The cells highly expressed Desmin by immunofluorescence. With the prolongation of culture time in vitro, round cells were gradually changed into star-shaped cells, and the expression of α-smooth muscle actin and type I collagen gradually increased. This study successfully established the high-performance and stable method for isolation of mouse primary hepatic stellate cells, providing a technical scheme for obtaining high-purity and high-viability mouse primary hepatic stellate cells, and also providing a technical support for research on the mechanism of liver fibrosis.

    中国组织工程研究杂志出版内容重点:干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程

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    Culture and identification of adult autologous neural stem cells from abandoned brain tissues during surgery in patients with intracranial aneurysm
    Wang Jia, Zhao Quan-jun, Hei Bo, Wang Zhao-tao, Sun Yi-kun, Wang Tao, Cui Shao-jie, Wang Pei-xin
    2018, 22 (21):  3381-3386.  doi: 10.3969/j.issn.2095-4344.0904
    Abstract ( 380 )   PDF (778KB) ( 315 )   Save

    BACKGROUND: A large number of studies on neural stem cell culture have been carried out in aborted fetus, fetal and adult mice, but there are few studies on adult human neural stem cell culture.
    OBJECTIVE: With the improvement of primary cell culture, to culture and identify adult autologous neural stem cells from the abandoned brain tissues around hematoma cavity during surgery in patients with aneurysm rupture, and then to study the cell cryopreservation and recovery so as to establish the adult autologous neural stem cell bank.
    METHODS: Over 500 mg abandoned brain tissues were collected during surgery from the surrounding tissues of hematoma cavity in three cases of aneurysm rupture. Adult autologous neural stem cells were cultured in serum-free medium with small tissue piece culture method. Cell growth was investigated by inverted phase contrast microscope. The expression of nestin, the specific antigen of neural stem cells, was confirmed by immunofluorescence method. Culture medium containing 4% fetal bovine serum was used to induce adherent growth of neural stem cells. Subculture was carried out when the cells proliferated to a certain number. Neural stem cells partially cryopreserved were used to establish the adult autologous neural stem cell bank. Recovered cells continued to subculture and induce differentiation. The cell differentiation was induced in the culture medium containing 10% fetal bovine serum. Expression of glial fibrillary acid protein (GFAP; marker for astrocytes), β-tublin (marker for neurons) and SOX10 (marker for oligodendrocytes) was detected by immunofluorescence method.
    RESULTS AND CONCLUSION: Nestin-positive neurospheres were successfully obtained from the abandoned brain tissues in the three cases through the improved serum-free medium culture. The cells could be amplified in vitro and handed from generation to generation. When cultured in the medium containing 10% fetal bovine serum, neurospheres were differentiated into β-tublin-positive neurons, SOX10-positive oligodendrocytes and GFAP-positive astrocytes. After subculture, passage 5 cells were still positive for nestin and maintained their characteristics of stemness. After recovery, the cryopreserved cells could grow well, still be positive for Nestin and be passed and amplified continuously. It is proved that neural stem cells can be obtained from abandoned brain tissues in different regions (lower frontal lobe and temporal lobe) around the hematoma cavity in patients with aneurysm rupture. These cells can differentiate into neurons, oligodendrocytes and astrocytes. Autologous neural stem cells transplantation is likely to promote the repair of neural function from laboratory to clinical application.

    中国组织工程研究杂志出版内容重点:干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程

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    Growth and differentiation of neural stem cells on a keratin fiber scaffold carrying nerve growth factor
    Sun Quan, Li Ying, Gao Yu-dan, Hao Peng, Zhao Wen, Duan Hong-mei, Yang Zhao-yang, Li Xiao-guang
    2018, 22 (21):  3387-3392.  doi: 10.3969/j.issn.2095-4344.0533
    Abstract ( 304 )   PDF (863KB) ( 255 )   Save

    BACKGROUND: It is essential for nerve tissue engineering is to construct a three-dimensional biomaterial scaffold carrying nerve cells, which has huge potential for repair of injured nervous system.
    OBJECTIVE: To seek the optimal concentration of hydrochloric acid used to treat keratin fibers based on the physical and chemical properties of keratin fibers, and to explore the effect of keratin fibers carrying nerve growth factor (NGF) on the differentiation of neural stem cells.
    METHODS: Keratin fibers were treated by hydrochloric acid of various concentrations, and their chemical properties were anlayzed by Fourier transform infrared spectroscopy. Then, we determined the optimal concentration of hydrochloric acid to treat keratin fibers. Subsequently, NGF was loaded onto the keratin fibers as shown by the Fourier transform infrared spectroscopy. Neural stem cells were co-cultured with keratin fibers with or without NGF for 10 days, and the expression of MAP2, MBP, GFAP and the percentage of nerve cells were thereafter detected by immunofluorescence.
    RESULTS AND CONCLUSION: The highest content of exposed carboxyl on the fiber surface appeared after treatment of keratin fibers with 8 mol/L hydrochloric acid. After 10 days of co-culture, the percentage of nerve cells was significantly higher in the keratin fiber-NGF group than the keratin fiber and control groups. Findings from the present study indicate that co-culture with keratin fibers carrying NGF can dramatically increase the percentage of nerve cells differentiating from neural stem cells.

    中国组织工程研究杂志出版内容重点:干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程

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    Microvesicles and exosomes in the lung diseases
    Luo Deng, Ran Wen-zhuo, Ye Ying-chun, Gao Ling
    2018, 22 (21):  3393-3400.  doi: 10.3969/j.issn.2095-4344.0516
    Abstract ( 439 )   PDF (799KB) ( 316 )   Save

    BACKGROUND: Microvesicles/exosomes as mediators for intercellular transfer can improve function of recipient cells, protect damaged tissues and predict the development of diseases. They have the potential to become a new treatment strategy for a variety of lung diseases.
    OBJECTIVE: To explore the application of microvesicles/exosomes in lung diseases.
    METHODS: The authors retrieved PubMed, CNKI and WanFang databases for relative articles addressing the application of stem cell-derived microvesicles/exosomes in lung diseases published from January 2007 to December 2017. The keywords were “exosome, microvesicle, microparticle, extracellular vesicles, lung, pulmonary, pneumonic, pulmonary, pulmonic” in English and Chinese, respectively. The irrelative and repetitive literatures were excluded.
    RESULTS AND CONCLUSION: Finally 68 eligible literatures were enrolled based on the inclusion and exclusion criteria. Microvesicles/ exosomes cannot be phagocytosed because of their small diameter. They play a pivotal role in cell-to-cell communication depending on mRNAs, microRNAs and proteins within them. As a new paracrine protein involved in the physiological and pathological microenvironment, microvesicles/exosomes may be the promising strategy for the diagnosis or prognostic prediction of lung diseases. Microvesicles/exosomes carrying bioactive substances promote angiogenesis, cell proliferation and migration. They are deemed to be a potential target for the modulation of lung diseases. In addition, microvesicles/exosomes can relieve edema, reduce pro-inflammatory cytokine secretion and promote injury repair in animal respiratory disease models. Compared to the traditional therapy, they have more advantages in diagnosis and prognosis of lung diseases. However, the use of microvesicles/exosomes is still at its initial stage. A series of problems, including sources, active constituent and dosage of microvesicles/exosomes, are needed to be resolved in the future.

    中国组织工程研究杂志出版内容重点:干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程

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    Nasopharyngeal carcinoma stem cells: surface markers, occurrence and development mechanisms, and targeted therapy
    Yao Xi, Wei Zheng-bo, Xie Ying
    2018, 22 (21):  3401-3409.  doi: 10.3969/j.issn.2095-4344.0520
    Abstract ( 447 )   PDF (810KB) ( 255 )   Save

    BACKGROUND: Nasopharyngeal carcinoma is a malignant tumor of the head and neck with distinct regional characteristics and radiosensitivity. Because of occult lesions and lymph node metastasis, it is mostly found in the moderate and advanced stage. Incomplete treatment makes it easy to relapse, which is the main reason for poor prognosis. With the continuous development of stem cell research, nasopharyngeal carcinoma stem cells have received increasing attention in recent years. Post-treatment residue is most likely to be responsible for the recurrence and metastasis of nasopharyngeal carcinoma.
    OBJECTIVE: To review the research progress in the isolation, identification, related signaling pathways and targeted therapies of nasopharyngeal carcinoma stem cells.
    METHODS: The first author searched PubMed and CNKI between 2003 and 2017 using the keywords of “nasopharyngeal carcinoma, stem cell, cancer stem cells, side population cells, selection, signaling pathway, therapy” in English and Chinese, respectively. Seventy-six eligible articles were finally chosen for review, after excluding unrelated or repetitive articles.
    RESULTS AND CONCLUSION: The included studies in this review provide useful information, based on which we certainly understand the causes for susceptible recurrence, metastasis and drug resistance of nasopharyngeal carcinoma. As a great progress is being made by studies regarding surface markers, related signaling pathways, pathogenic molecules and regulatory mechanisms of nasopharyngeal carcinoma stem cells involved, breakthroughs will be achieved both in the clarification of nasopharyngeal carcinoma initiation and development and in searching new therapies targeting nasopharyngeal carcinoma stem cells.

    中国组织工程研究杂志出版内容重点:干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程

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    Research progress and tendency of mesenchymal stem cell transplantation in the treatment of spinal cord injury
    Liu Ke-xun, Huo Hong-jun, Zhao Yan, Zuo Yuan
    2018, 22 (21):  3410-3416.  doi: 10.3969/j.issn.2095-4344.0905
    Abstract ( 313 )   PDF (819KB) ( 296 )   Save

    BACKGROUND: Mesenchymal stem cells have the advantages of convenient for drawing materials and easy to separate and culture, and have many characteristics, such as regulating immune response, supporting hematopoiesis, inhibiting excessive inflammatory reaction, and promoting angiogenesis. Transplantation of mesenchymal stem cells to treat spinal cord injury can bring new hope for the rehabilitation of spinal cord injury patients.
    OBJECTIVE: To summarize and discuss the recent progress, existing problems and development trend of mesenchymal stem cells in the treatment of spinal cord injury.
    METHODS: Relevant articles published from 2000 to 2017 were retrieved from CNKI and PubMed databases. The key words were “mesenchymal stem cells; spinal cord injury; cell transplantation; combined treatment” in Chinese and English, respectively. The old and repeated views were excluded, and 71 eligible articles were included in the literature review.
    RESULTS AND CONCLUSION: Studies on mesenchymal stem cell transplantation for the treatment of spinal cord injury mostly focus on basic and animal studies. Simple mesenchymal stem cell transplantation is limited in the treatment of spinal cord injury. Mesenchymal stem cells combined with cells, drugs and biological scaffolds are widely used to treat spinal cord injury, which cannot only play a therapeutic role in spinal cord injury, but also expand the advantages of mesenchymal stem cells. Finding the best partner of mesenchymal stem cells with little influence on human body and transplanting autologous mesenchymal stem cells to treat spinal cord injury will become the developmental trend of spinal cord injury treatment.

    中国组织工程研究杂志出版内容重点:干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程

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    Type I collagen induction of bone marrow mesenchymal stem cells and the mechanism of osteogenesis
    Xie Yu, Zhou Nuo
    2018, 22 (21):  3417-3423.  doi: 10.3969/j.issn.2095-4344.0906
    Abstract ( 390 )   PDF (817KB) ( 295 )   Save

    BACKGROUND: Type I collagen is the main component of the extracellular matrix of bone tissue. Numerous studies have shown that it has the ability to induce osteogenic differentiation, and plays an important role in the process of bone mineralization. Currently, bionic materials are being developed as an alternative to type I collagen in the field of biological materials.
    OBJECTIVE: To review the mechanism of osteogenesis induced by type I collagen, the role of type I collagen in the biomineralization process, and the real-time expression of type I collagen during distraction osteogenesis.
    METHODS: With the key words of “type I collagen, bone marrow mesenchymal stem cells, osteoblast, distraction osteogenesis, mineralization” in Chinese and English, we performed a computer-based search in CNKI and PubMed database for relevant articles published from 1990 to 2017. Finally, 58 eligible articles were included in result analysis.
    RESULTS AND CONCLUSION: Type I collagen induces osteogenic differentiation of bone marrow mesenchymal stem cells and osteoblasts mainly through collagen-integrin signaling pathways. In the early stage of distraction osteogenesis, type I collagen is less secreted, but the secretion increases in the middle and later stages, eventually becoming the main component of extracellular matrix. There are two mainstream theories of mineralization mechanisms: (1) Type I collagen plays a role as a template scaffold in biomineralization, guiding the deposition and mineralization of calcium. (2) Amorphous calcium phosphate infiltrates between collagen fibers and changes from amorphous to crystalline state, forming an aligned crystal structure.

    中国组织工程研究杂志出版内容重点:干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程

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    Adipose-derived stem cells in cartilage tissue engineering: cell markers, genetic modifications, and the ideal combination with scaffolds
    Wei Yi-fan, Zeng Jing, Zhang Wei, Wang Yao, Chen You-bai, Han Yan
    2018, 22 (21):  3424-3430.  doi: 10.3969/j.issn.2095-4344.0489
    Abstract ( 493 )   PDF (824KB) ( 231 )   Save

    BACKGROUND: Cartilage injury and defect have always been a challenge to orthopedic and plastic surgeons. Tissue engineering technology provides a novel promising approach to repair cartilage defects. Adipose-derived stem cells (ADSCs) are a great source of seed cells for cartilage tissue engineering due to the sufficient storage, easy harvest, high yield, easy isolation, strong proliferation and multilineage differentiation capability.
    OBJECTIVE: To analyze the factors that influence the construction of tissue-engineered cartilage using ADSCs as seed cells, to summarize the methods that verify a successful differentiation towards chondrocytes from ADSCs, to discuss some issues on the ADSCs based cartilage tissue engineering, and to look forward the future of cartilage tissue engineering.
    METHODS: On June 5, 2017, we searched in PubMed using the following strategy “(((adipose stem cell[Title]) OR adipose-derived stem cell[Title]) OR adipose-derived mesenchymal stem cell[Title]) AND chondrogenic differentiation[Title]”. On August 4, 2017, we searched in SinoMed using the following strategy “(“adipose-derived stem cell”[Title]) AND “cartilage”[Title]” in Chinese. We first selected literatures related to ADSC differentiation into chondrocyte or cartilage tissue engineering using ADSCs as seed cells according to their titles and abstracts. We then read the titles of the references of the selected literatures and reselected the articles associated with the same topic from the references and removed the repetitive literatures.
    RESULTS AND CONCLUSION: There were 35 eligible literatures in PubMed, among which 30 were published in recent 5 years. There were 71 eligible literatures in SinoMed, among which 9 were reviews and 22 were published in recent 5 years. Finally, 60 literatures were included for this review. Growth factors such as transforming growth factor β, bone morphogenetic protein, insulin-like growth factor can facilitate the ADSCs differentiation towards chondrocytes. The combination of several growth factors and gene modification of ADSCs utilizing the above-mentioned growth factor genes for a long-term stable release are in the spotlight of current research. Traditional induction medium recipe consisting of dexamethasone, insulin, vitamin C and several growth factors is still the mainstream in the current market. Cell culture methods such as coculture, microsphere, scaffold, and dynamic three-dimensional culturing system can promote the efficiency and quality of the construction of tissue engineered cartilage. However it is essential to find an ideal scaffold material. Furthermore, other factors including ADSCs source, culture conditions, miRNA, platelet rich plasma, parathyroid hormone related peptides can also affect the ADSCs differentiation towards chondrocytes. Besides the morphological changes of induced ADSCs, the chondrogenic differentiation can also be verified through dyeing or the detection of specific genes and proteins such as Sox9, Collagen II, chondroitin sulfate, and keratansulfate. The future research interest will focus on the specific marker of ADSCs, the sequence and dose of exogenous growth factors for combined utility, gene-modified ADSCs and scaffold materials.

    中国组织工程研究杂志出版内容重点:干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程

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    Stem cell therapy for thalassemia: present and future
    Hu Jun-jie, Chen Xin-ping, Fu Sheng-miao
    2018, 22 (21):  3431-3437.  doi: 10.3969/j.issn.2095-4344.0532
    Abstract ( 707 )   PDF (723KB) ( 331 )   Save

    BACKGROUND: Methods of blood transfusions and regular iron removal have been gradually introduced in thalassemia patients since the 1980s. However, this method is limited by the need of a large amount of social resources to be widely used. With the continuous progress of stem cell research in recent years, there is a new hope of using stem cell technology to treat thalassemia.
    OBJECTIVE: To review the therapeutic effect of stem cell therapy on thalassemia.
    METHODS: The first author searched relevant articles with PubMed database and CNKI (from 1989 to 2017) using the key words of “thalassemia, hematopoietic cell transplantation, therapy, stem cell” in English and “thalassemia, stem cell therapy, transplantation” in Chinese, respectively. After initial screening, 51 articles were retained.
    RESULTS AND CONCLUSION: Prior to the use of stem cells to treat patients with thalassemia, a reasonable drug conditioning program and a proper donor source can increase the survival rate, and reduce the incidence of rejection and graft-versus-host disease after transplantation. At the same time, the age of recipients and the level of risk assessment are important reference factors in the transplantation process, which directly affect the effect of stem cell transplantation. In addition, choosing the appropriate type of stem cells, improving the transplantation method, and optimizing drug conditioning can reduce complications and risks of transplantation, and improve the quality of life of thalassemia patients.

    中国组织工程研究杂志出版内容重点:干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程

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    Role of SIRT1 in mesenchymal stem cell differentiation
    Wang Gang-gang, Song Wei
    2018, 22 (21):  3438-3444.  doi: 10.3969/j.issn.2095-4344.0526
    Abstract ( 374 )   PDF (703KB) ( 299 )   Save

    BACKGROUND: Mesenchymal stem cells (MSCs) can be induced into osteoblast, condrocytes, adipocytes, cardiomyocytes and nerve cells in vitro. MSCs characterized by multi-lineage differentiation, easy separation and culture have been widely used in stem cell therapy and tissue engineering research. SIRT1, a protein deacetylase widely distributing in mammals, has been proved to control the proliferation and differentiation of MSCs through regulating related genes.
    OBJECTIVE: To summarize the effects of SIRT1 on MSCs differentiation, focusing on signal pathways and other related factors regulation.
    METHODS: The keywords of “SIRT1, mesenchymal stem cells, differentiation” were searched in CNKI, PubMed and Elsevier for related papers. Irrelevant, outdated and repetitive articles were excluded, and the remaining 49 articles were included for further analysis.
    RESULTS AND CONCLUSION: MSCs have the potential of self-renewal and multi-lineage differentiation via Wnt, transforming growth factor β and other signal pathways. SIRT1 influences the self-renewal and multi-lineage differentiations of MSCs, including up-regulation of osteogenic, chondrogenic and myogenic differentiations and down-regulation of adipogenic differentiation, and the underlying mechanism is to regulate the expression, activity and location of intermediate proteins in signal pathways and differentiation-related transcription factors.

    中国组织工程研究杂志出版内容重点:干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程

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