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    18 June 2017, Volume 21 Issue 17 Previous Issue    Next Issue
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    Liver X receptor reverses the inhibitory effects of propofol on bone marrow mesenchymal stem cells
    Zhang Yong-qiang, Liu Jun, Chen Sheng-yang, Liu Guo-ze, Tian Jian-min, Yue Xiu-qin
    2017, 21 (17):  2625-2630.  doi: 10.3969/j.issn.2095-4344.2017.17.001
    Abstract ( 288 )   PDF (1606KB) ( 206 )   Save

    BACKGROUND: Studies have shown that propofol enables a reduction in the number of adult rat mesenchymal stem cells, while the cell differentiation is also significantly inhibited.
    OBJECTIVE: To explore whether liver X receptors (LXRs) can reverse the inhibitory effects of propofol on bone marrow mesenchymal stem cells.
    METHODS: Fifteen healthy C57/BL6 mice were randomized into three groups, 5 of which served as blank control group (intraperitoneally treated with normal saline), 5 as propofol treatment group (intraperitoneally treated with 60 mg/kg propofol), and 5 as propofol + LXRs agonist treatment group (intraperitoneally injected with 10 μL/g LXRs at the 1st day, and then injected with 60 mg/kg propofol at the 2nd day). The mice in the three groups were killed at 1-3 hours after treatment to isolate and culture bone marrow mesenchymal stem cells. Cell counting kit-8 and clone formation assay were used to evaluate the abilities of cell proliferation and self-renewal; induced differentiation experiments in vitro were used to evaluate the differentiation ability of cells into adipocytes, osteoblasts and chondrocytes; real-time quantitative PCR was used to detect the expression of differentiation related molecules and Notch signal.
    RESULTS AND CONCLUSION: In the propofol-treated mice, cell viability and clone forming ability as well as adipogenic, osteogenic and chondrogenic differentiation of cells decreased significantly compared with the blank control group (P < 0.05), while LXR agonists could reverse these effects significantly (P < 0.05). Notch signal expressions showed no difference among three groups prior to induced differentiation. The expression levels differentiation related molecules downregulated significantly after propofol treatment (P < 0.05), but upregulated significantly after treatment with LXR agonists (P < 0.05). Notch signaling inhibitor treatment could significantly inhibit the multi-directional differentiation of bone marrow mesenchymal stem cells in the three groups. All these findings indicate that activated LXRs can reverse the inhibitory effects of propofol on bone marrow mesenchymal stem cells.

     

     

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    Optimization of repeated freeze-thaw and ultrasonication for collection of lysate of adipose-derived stem cells
    Wang Jun-yi, Jin Yin-peng, Li Hong-chao, Meng Ling-yu, Li Li, Wang Xiao-jin, Zhou Rong, Chen Cheng-wei, Fu Qing-chun, Cheng Ming-liang
    2017, 21 (17):  2631-2637.  doi: 10.3969/j.issn.2095-4344.2017.17.002
    Abstract ( 451 )   PDF (1411KB) ( 313 )   Save

    BACKGROUND: It has been believed mesenchymal stem cells (MSCs) play a role in treatment through paracrine mechanism. Various side effects such as embolism, tumorigenesis and immunological reaction caused by direct injection of MSCs can be avoided by extracting MSC lysate. However, there is a larger difference in current collection methods and standards of MSC lysate.
    OBJECTIVE: To compare repeated freeze-thaw and ultrasonication for the collection of lysate of MSCs.
    METHODS: Adipose-derived mesenchymal stem cells (ADMSCs) were isolated from the abdominal subcutaneous fat of healthy individuals, and purified with adherence screening method, followed by in vitro amplification using fetal bovine serum medium. The common surface makers of these cells were tested by flow cytometry (1×109, 2×109, 4×109/L). Repeated freeze-thaw and ultrasonication were employed for cell cytoclasis at three different densities respectively in saline and double distilled water, and a comprehensive comparison was performed on cytoclasis rate and the content of protein in cell lysate between the two methods.
    RESULTS AND CONCLUSION: (1) ADMSCs obtained from in vitro isolated human adipose tissue grew in a swirl or radial pattern with a homogenous size and neat arrangement. CD44, CD90, CD105 and other commonly used surface markers were highly expressed. (2) The study for optimization of lysate collection revealed that the higher cell density implicated a longer time for cell wall disruption and cytoclasis, as well as significantly increased cytoclasis rate. (3) BCA protein assay showed that the highest content of protein was obtained in saline solvent using ultrasonication method. Comprehensive analysis on the results leads to a conclusion that ultrasonication method with saline as the solvent is the optimized method for extraction of ADMSCs lysate, and the cell concentration of less than 4×109/L is recommended.

     

     

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    Adipogenic capacity of CD54+/CD54- adipose-derived stem cells
    Li De-quan, Liang Zhi-jie, Wei Jin-ru, Huang Hai, Huang Min-hong, Chi Gang-yi, Li Hong-mian
    2017, 21 (17):  2638-2643.  doi: 10.3969/j.issn.2095-4344.2017.17.003
    Abstract ( 326 )   PDF (3892KB) ( 203 )   Save

    BACKGROUND: Studies have shown that adipose-derived stem cells have pluripotent differentiation potential, but only 30%-40% of cells can differentiate into mature adipocytes with low adipogenic differentiation potential. Therefore, how to improve the adipogenic differentiation ability of adipose-derived stem cells is a key problem to be solved in the process of soft tissue regeneration.

    OBJECTIVE: To observe the relationship between the surface marker CD54 of rabbit adipose-derived stem cells and their adipogenic capacity, and to explore the adipogenic differentiation of CD54+/CD54- adipose-derived stem cells under the same induction.
    METHODS: We successfully isolated and cultured the adipose-derived stem cells from inguinal subcutaneous fat pads (3 ml) of New Zealand white rabbits, aged 8-12 weeks, which were induced into multi-differentiation and used to detect surface markers. We sorted the passage 3 adipose-derived stem cells by immunomagnetic beads and divided into two categories including CD54+ and CD54- adipose-derived stem cells. After 14 days of adipogenic induction, the cells in the two groups were subjected to oil red O staining and were compared by detecting the density of mature adipocytes and lipid droplet contenT.

    RESULTS AND CONCLUSION: The cultured adipose-derived stem cells possessed the characteristics of mesenchymal stem cells that could differentiate into mature adipocytes, osteoblasts and chondrocytes, with CD29, CD44, CD49d, CD54, CD73, CD90 and CD105 positive expression while CD31, CD34 and CD45 negative expression. Fourteen days after adipogenic induction, the density of mature adipocytes and the intracellular lipid droplet content in the CD54+ group were significantly higher than those in the CD54- group (P < 0.05). We also found that the mRNA expressions of PPARγ, ADD1, C/EBPα related to adipogenic differentiation in the CD54+ group were significantly higher than those in the CD54- group (P < 0.05). Taken together, CD54+ adipose-derived stem cells have excellent adipogenic differentiation capacity.

     

     

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    Optimization of Raman spectra acquisition conditions and its application in a comparison study on mesenchymal stem cells and embryonic stem cells
    Chen Ming, Cheng Xue-lian, Duan Yong-juan, Hu Xiao
    2017, 21 (17):  2644-2651.  doi: 10.3969/j.issn.2095-4344.2017.17.004
    Abstract ( 318 )   PDF (4850KB) ( 261 )   Save

    BACKGROUND: Raman spectrum, compared with conventional detection technologies, is a rapid, non-invasive and label-free optical method. Its application has become an issue of concern in biomedical research. However, further studies are warranted to optimize the acquisition condition of Raman spectra from different stem cells.
    OBJECTIVE: To explore the effect of the wavelength of laser and the groove frequency of gratings to obtain the optimized parameter combination for Raman spectrum collection in human stem cells.
    METHODS: Using human mesenchymal stem cells as samples, the effects of different laser wavelengths (532, 638, 785 nm) and different grating groove frequency (600, 1 200, 1 800 gr/mm) on Raman spectra were compared respectively. Then the different combinations of the wavelength and groove frequency were used and compared in terms of the spectra resolution and acquisition time, and the best acquisition condition was selected and applied in a comparison study on the Raman spectra from human mesenchymal stem cells and human embryonic stem cells.
    RESULTS AND CONCLUSION: The wavelengths of lasers and groove frequencies of gratings showed compound impacts on both the spikes at different wavenumbers and the ratio between spikes; the combination of 785 nm and 1 200 gr/mm was confirmed to be the best spectrum features for human mesenchymal stem cells. The comparison of Raman spectra from human mesenchymal stem cells and human embryonic stem cells implies that the embryonic stem cells contain higher nucleic acids than the mesenchymal stem cells, while the mesenchymal stem cells appear to contain more proteins and lipids.

     

     

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    Effects of platelet-rich plasma on the proliferation and osteogenic differentiation of human umbilical cord mesenchymal stem cells
    Yang Kai, Cheng Ya-dong, Wang Peng, Wu Tong, Li Shu-shan, Min You-hui
    2017, 21 (17):  2652-2658.  doi: 10.3969/j.issn.2095-4344.2017.17.005
    Abstract ( 261 )   PDF (5151KB) ( 289 )   Save

    BACKGROUND: Studies have demonstrated that platelet-rich plasma can promote osteogenesis and proliferation of bone marrow mesenchymal stem cells, adipose-derived stem cells and skeletal muscle satellite cell, but whether it can promote the proliferation and osteogenesis of human umbilical cord mesenchymal stem cells (hUC-MSCs) is unclear.

    OBJECTIVE: To investigate the effects of different concentrations of platelet-rich plasma on the proliferation and osteogenic differentiation of hUC-MSCs.
    METHODS: Passage 5 hUC-MSCs were cultured in medium containing different concentrations of platelet-rich plasma (0, 250, 500, 750, 1 000, 2 000 ng/L), respectively. Cell proliferation was detected at 1, 3, 5, 7 days after culture, and the best platelet-rich plasma mass concentration was screened. Afterwards, passage 5 hUC-MSCs were divided and cultured in complete medium (blank control group), optimal concentration of platelet-rich plasma (platelet rich plasma group), osteogenesis induction medium (osteogenic induction group), or the osteogenesis induction medium containing the optimal concentration of platelet-rich plasma (combined group). Cell activity of alkaline phosphatase was detected after cultivated for 3, 7, 14 days. Osteopontin, bone specific transcription factor, and osteocalcin mRNA relative expression levels were detected after cultivated for 7, 14, 21 days. Mineralization of the extracellular matrix was detected after cultivated for 21 days.

    RESULTS AND CONCLUSION: After 5 and 7 days of culture, the cell proliferation was higher in 500, 750, 1 000 ng/L platelet-rich plasma groups than 0 ng/L group (P < 0.05), and 750 ng/L platelet-rich plasma showed the best effect on cell proliferation, which was used in the following experiments. Compared with the other groups, the combined group had significantly increased alkaline phosphatase activity (P < 0.05), and up-regulated osteopontin, bone specific transcription factor and osteocalcin mRNA relative expression levels (P < 0.05) at different culture times. In addition, the degree of extracellular matrix mineralization in the combined group was also higher than that in the other three groups (P < 0.05). To conclude, 750 ng/L platelet-rich plasma can promote hUC-MSCs proliferation and osteogenic differentiation.

     

     

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    Hepatic failure patient’s serum before and after plasmapheresis induces the differentiation of umbilical cord mesenchymal stem cells into hepatic cells
    Wang Jing-bo, Geng Da-ying, Li Xiao-ying, Chen Li, Xu Feng, Shi Zhao-zhang
    2017, 21 (17):  2659-2664.  doi: 10.3969/j.issn.2095-4344.2017.17.006
    Abstract ( 401 )   PDF (3736KB) ( 241 )   Save

    BACKGROUND: Umbilical cord mesenchymal stem cells (UC-MSCs) have made certain curative effect on hepatic failure, but little is reported on the effect of hepatic failure patient’s serum microenvironment on UC-MSCs differentiation ability.
    OBJECTIVE: To investigate the effect of hepatic failure patient’s serum on the differentiation of umbilical cord mesenchymal stem cells into hepatic cells.
    METHODS: UC-MSCs were isolated by tissue adherent method and the cell morphology and phenotype identified by microscope and flow cytometry. Alpha-MEM media with serum before/after plasmapheresis were used to culture the third generation of UC-MSCs, and regular fetal bovine serum culture medium acted as control group. Inverted microscope was used to observe the cell morphology in three groups. Immunohistochemical method was used to measure expression level of alpha fetoprotein, albumin and cytokeratin 18.
    RESULTS AND CONCLUSION: A great amount of high-purity UC-MSCs could be obtained using tissue adherent method, which highly expressed CD44, CD73, CD90, CD10, but did not express CD45. Hepatic failure patient’s serum could change the morphology of UC-MSCs and induce UC-MSCs to express alpha fetoprotein, albumin and cytokeratin 18. The positive expression of alpha fetoprotein, albumin and cytokeratin 18 was significantly increased after plasmapheresis (P < 0.05). To conclude, hepatic failure patient’s serum after plasmapheresis exert more benefits to induce UC-MSCs to differentiate into hepatic cells than that before plasmapheresis.

     

     

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    Clinical application of human umbilical cord-derived mesenchymal stem cells in liver transplantation patients
    Chen Rong, Jiang Tao, Yang Ai-zhen, Zhang Dong-hua, Wang Xuan
    2017, 21 (17):  2665-2671.  doi: 10.3969/j.issn.2095-4344.2017.17.007
    Abstract ( 317 )   PDF (935KB) ( 317 )   Save

    BACKGROUND: In recent years, the immunoregulatory effects of mesenchymal stem cells (MSCs) can be used to induce immune tolerance.

    OBJECTIVE: To evaluate the safety and feasibility of human umbilical cord-derived MSCs (hUC-MSCs) in liver transplantation patients.
    METHODS: hUC-MSCs were cultured and identified. After approved by the Medical Ethics Committee, a total of 50 patients were randomly divided into experimental group and control group according to the proportion of 1:1. In the experimental group, hUC-MSCs were perfused by the portal vein during the operation and infused into the jugular vein on the 3rd day after the operation. The injection dose was 1×106/kg (prepared as 50 mL of cell suspension). Both groups received standard immunosuppressive regimens. Blood biochemistry and immune function indicators were detected preoperatively and at postoperative days 3, 7, months 1, 2, 3, 6, 12. Acute and chronic rejection rates, incidence of infection, and incidence of transplantation-related complications were recorded.

    RESULTS AND CONCLUSION: (1) At 3 and 7 days after the operation, the percentage of peripheral blood CD4+CD25+ cells (regulatory T cells) in the experimental group was significantly higher than that in the control group (P < 0.05). The percentage of CD4+ cells (helper/inducer T cells) and ratio of CD4+/CD8+ T lymphocytes were significantly lower in the experimental group than the control group (P < 0.05). (2) There was no significant difference in postoperative alanine aminotransferase and total bilirubin levels between the two groups (P > 0.05). (3) The incidence of abnormal liver function in the experimental group was significantly lower than that in the control group (P < 0.05). (4) The incidence of transplantation-related complications and the rate of infection showed no significant difference between the two groups (P > 0.05). Overall, the intravenous infusion of hUC-MSCs is safe and feasible in liver transplantation patients, which in early stage can promote the the proliferation and activation of CD4+CD25+ cells (regulatory T cells), reduce the percentage of CD4+ cells (helper/inducer T cells) and lower the ratio of CD4+/CD8+ T cells, thereby improving the immune status in liver transplantation patients.

     

     

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    RNA interference targeting inhibition of TRAP1 suppresses cell growth and promotes apoptosis in CD133+CD44+ laryngeal carcinoma stem cells
    Xue Hai-tao, Su Jing, Chen Shuai, Chen Chun-ju, Zhang Ji-hua, Tian Jun-hai, Dong Kai-feng
    2017, 21 (17):  2672-2677.  doi: 10.3969/j.issn.2095-4344.2017.17.008
    Abstract ( 367 )   PDF (1050KB) ( 192 )   Save

    BACKGROUND: Tumor necrosis factor-associated protein 1 (TRAP1) is a heat-shock protein 90-related mitochondrial chaperone. Accumulative evidence has demonstrated that TRAP1 overexpression is closely related to carcinogenesis. However, the exact function and mechanism of TRAP1 in the occurrence of laryngeal carcinoma remains unclear.

    OBJECTIVE: To investigate whether RNA interference can inhibit TRAP1 overexpression and to explore its effects on growth and apoptosis of CD133+CD44+ laryngeal carcinoma stem cells.
    METHODS: CD133+CD44+ laryngeal carcinoma stem cells were sorted from human laryngeal carcinoma Hep-2 cells using immunomagnetic beads. The shRNA sequence of TRAP1 was designed and synthesized and CD133+CD44+ laryngeal carcinoma stem cells were transfected with LipofectamineTM 2000. Cell counting kit-8 assay, colony formation assay and flow cytometry were used to investigate the effects of interference of TRAP1 expression on growth and apoptosis of CD133+CD44+ laryngeal carcinoma stem cells. Spectrophotometric method was used to detect the activity of caspase-3, -8 and -9.

    RESULTS AND CONCLUSION: TRAP1 mRNA and protein expression levels were significantly decreased in TRAP1 shRNA-transfected CD133+CD44+ laryngeal carcinoma stem cells (P < 0.01). Compared with the blank control and negative control groups, the growth and colony formation of CD133+CD44+ laryngeal carcinoma stem cells were significantly inhibited in the TRAP1 shRNA-transfected group (P < 0.05). Apoptosis of CD133+CD44+ laryngeal carcinoma stem cells was significantly inhibited in the TRAP1 shRNA-transfected group as compared with the blank control and negative control groups (P < 0.05). TRAP1 shRNA-mediated cell apoptosis was associated with the activation of caspase-3, -8 and -9. These results suggest that RNA interference targeting inhibition of TRAP1 suppresses cell growth but promotes apoptosis in CD133+CD44+ aryngeal carcinoma stem cells. TRAP1 is likely to be a gene target for treatment of laryngeal carcinoma.

     

     

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    Ultrasound mediated nitric oxide microbubbles enhance the therapeutic efficacy of bone marrow mesenchymal stem cell transplantation on myocardial infarctions
    Chen Fei, Xu Peng, Qiao Qi, Fan Bing, Tong Jia-yi, Fan Guo-feng
    2017, 21 (17):  2678-2683.  doi: 10.3969/j.issn.2095-4344.2017.17.009
    Abstract ( 352 )   PDF (1058KB) ( 194 )   Save

    BACKGROUND: Recent experimental studies have found ultrasound mediated microbubbles potentiate stem cell therapy in myocardial infarction (MI)-induced heart failure, indicating a good application prospect. But whether ultrasound mediated nitric oxide (NO) microbubbles also have the same effect in the intracoronary transplantation of bone marrow mesenchymal stem cells (BMSCs) for treatment of large animals with MI is still unknown.

    OBJECTIVE: To investigate the effectiveness and possible mechanism of ultrasound mediated NO microbubbles in potentiating intracoronally transplanted BMSCs homing to the infarcted area in a MI pig model.
    METHODS: Density gradient centrifugation culture method was used in the isolation and cultivation of BMSCs. CM-Dil was used to label BMSCs in vitro. Twenty-four pigs were used to make MI models by blocking the left anterior descending coronary artery, and then were divided into PBS group, BMSCs group, ultrasound+microbubbles+BMSCs (MB) group, ultrasound+NO microbubbles+BMSCs (NO-MB) group(n=6 per group). In the PBS group, 10 mL of PBS was intracoronally injected. In the BMSCs group, about 1×107 BMSCs were diluted in 10 mL of PBS and then intracoronally infused. In the MB group, 0.1 mL/kg sulphur hexafluoride microbubbles (Sono Vue) was intracoronally injected together with ultrasound treatment (1 MHz, 2 W/cm2, 2 minutes), followed by intracoronary infusion of about 1×107 BMSCs that were diluted in 10 mL of PBS. In the NO-MB group, all methods and conditions were identical to those in the MB group except only 0.1 mL/kg of Sono Vue was replaced by 0.1 mL/kg NO microbubbles. Three pigs were sacrificed in each group 48 hours after CM-Dil positive BMSCs transplantation. The labeled BMSCs were observed and counted by fluorescent microscope after frozen sectioning of the infarct area. We assessed and compared left ventricular systolic function with M-mode ultrasound among groups at 4 weeks after intervention. After cardiac function test, the rest pigs were sacrificed and capillary density in the myocardial ischemic area was counted and compared after hematoxylin-eosin staining.

    RESULTS AND CONCLUSION: (1) The number of CM-Dil positive cells in the area of MI in the NO-MB group was much more than that in the MB group and BMSCs group with statistical significance (P < 0.05). (2) The left ventricle systolic function was significantly improved in the NO-MB group as compared with the MB group (P < 0.05). The same trend was observed between NO-MB group and BMSCs group as well as between NO-MB group and PBS group (P < 0.05). (3) The density of capillaries increased significantly in the NO-MB group compared with the MB group, BMSCs group and PBS group, respectively. To conclude, ultrasound mediated NO microbubble combined with intracoronary BMSCs transplantation can improve the left ventricular systolic function. The possible mechanism could be that ultrasound- mediated NO mocrobubbles promote the homing of transplanted BMSCs to the myocardial ischemia area as well as improve local angiogenesis.

     

     

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    Osteogenesis and expression of bone morphogenetic protein 2 after bone marrow mesenchymal stem cells combined with calf cortical bone with partial cancellous bone implanted into rabbits
    Chen Neng, Shao Yun-feng, Liu Tang, Zhang Xiang-sheng, Xiong Guang-zhong
    2017, 21 (17):  2684-2689.  doi: 10.3969/j.issn.2095-4344.2017.17.010
    Abstract ( 391 )   PDF (988KB) ( 186 )   Save

    BACKGROUND: Previous studies have confirmed that rabbit bone marrow mesenchymal stem cells (BMSCs) can differentiate into osteoblasts under osteogenic induction in vitro, stably express the specific phenotype of osteoblasts and have osteogenic ability. Calf cortical bone scaffold with partial cancellous bone has good biocompatibility and degradability, which can be used as a carrier material of bone marrow mesenchymal stem cells.
    OBJECTIVE: To combine rabbit BMSCs with calf bone composite according to the basic principles of bone tissue engineering and to observe the osteogenesis in the New Zealand white rabbits after implantation of BMSCs/calf bone composite into the ilium, thereby providing a direct evidence for preliminary clinical application of tissue-engineered bone products.
    METHODS: BMSCs/calf cortical bone scaffold with partial cancellous bone (tissue-engineered bone group), simple calf heterogeneous bone (heterogeneous bone group) or autologous iliac bone (autologous iliac bone group) was randomly implanted into the rabbit ilium. The changes of implant surface and tissue reactions around the implant were observed. X-ray examination was performed to observe osteogenic changes at 4, 8, 12, 24 weeks after implantation. Immunohistochemistry staining was used to observe the expression of bone morphogenetic protein 2.
    RESULTS AND CONCLUSION: After heterogeneous bone implantation, the wound healed well, and there were no systemic or local inflammation and toxicity reactions in all groups. The X-ray results showed that at postoperative 24 weeks, the implant was basically fused with the host bone in the tissue-engineered bone group, but the fusion was unsatisfactory in the heterogeneous bone group. The process of ossifications from cartilages was observed in all groups by hematoxylin-eosin staining, and bone morphogenetic protein 2 was positive for immunohistochemical staining. Findings from in vivo experiments indicate that rabbit BMSCs seeded onto the calf cortical bone scaffold with partial cancellous bone could construct tissue-engineered bone by osteoinductation in vitro in the rabbits.

     

     

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    Human adipose-derived mesenchymal stem cells promote liver cell regeneration by up-regulating the expression of proliferating cell nuclear antigen
    Shi Guang-jun, Zhang Ya-dong, Hu Yin-yin, Tan Xue-ying
    2017, 21 (17):  2690-2695.  doi: 10.3969/j.issn.2095-4344.2017.17.011
    Abstract ( 269 )   PDF (847KB) ( 273 )   Save

    BACKGROUND: Adipose-derived mesenchymal stem cells (ADMSCs) can improve the liver function of rats with liver failure, which illustrates the important research value in the field of tissue engineering and cell transplantation.
    OBJECTIVE: To evaluate the therapeutic potential of human ADMSCs in heart failure rats and to discuss the possible biological mechanisms involved.
    METHODS: Heart failure rats were randomized into model and ADMSCs groups, which were given normal saline or DAPI-labeled human ADMSCs (3.0×106) via the tail vein. At 1, 3, 7 days after transplantation, we detected the biochemical indexes for liver function in rats. At 3 days after transplantation, the serum levels of cytokines, such as tumor necrosis factor α and interleukin-10, were detected, the histomorphological changes in the liver were observed by hematoxylin-eosin staining, and the protein expression of proliferating cell nuclear antigen was detected by western blot.
    RESULTS AND CONCLUSION: We found that human ADMSCs could migrate to the liver and lung tissues in rats after the transplantation via the tail vein. At 1 and 3 days after transplantation, the levels of serum alanine aminotransferase and aspartate aminotransferase were significantly reduced in the ADMSCs group as compared with the model group (P < 0.05); furthermore, the secretion of tumor necrosis factor α and interleukin-10 was significantly suppressed at 3 days after cell transplantation (P < 0.05). The results of hematoxylin-eosin staining indicated a significant improvement in liver degeneration and necrosis. The expression of proliferating cell nuclear antigen protein in the ADMSCs group was significantly up-regulated compared with the model group. To conclude, human ADMSCs can inhibit the inflammatory reaction and up-regulate the expression of proliferating cell nuclear antigen, to promote the regeneration of liver cells and the recovery of liver function.

     

     

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    Effects of human umbilical cord mesenchymal stem cell therapy on the immune function and prognosis in patients with decompensated liver cirrhosis due to hepatitis B
    Fang Xue-qing, Zhang Jun-fei, Song Hai-yan, Chen Zhao-lin, Dong Jing, Pan Jin-jin, Chen Xi, Liu Bo, Chen Cong-xin
    2017, 21 (17):  2696-2701.  doi: 10.3969/j.issn.2095-4344.2017.17.012
    Abstract ( 310 )   PDF (855KB) ( 574 )   Save

    BACKGROUND: A large number of experiments in vivo and in vitro have shown that mesenchymal stem cells may obviously inhibit the lymphocytes and other immunocytes.

    OBJECTIVE: To investigate the effect of human umbilical cord mesenchymal stem cell transplantation on the immune function and prognosis of patients suffering decompensated liver cirrhosisn due to hepatitis B.
    METHODS: 118 patients with decompensated cirrhosis due to hepatitis B were randomly divided into control group (n=59) and observation group (n=59). The two groups all received normal medical treatment, and in addition, the observation group also received human umbilical cord mesenchymal stem cell transplantation. (4.0-4.5)×108 stem cells were transplanted twice by intervention via proper hepatic artery (10 mL) and intravenous infusion (10 mL) within 1 week after admission. The levels of serum interleukin-6, tumor necrosis factor-α, interleukin-10, transforming growth factor-β and the percentage of lymphocyte subsets in the peripheral blood were determined in the two groups before and 1, 4 weeks after treatment. The model for end-stage liver disease (MELD) score and Child-Pugh score of 118 patients after treatment for 12 weeks were observed and recorded, and liver failure, complications and survival during follow-up period in the two groups were observed.

    RESULTS AND CONCLUSION: After treatment for 1 and 4 weeks, the levels of serum interleukin-6 and tumor necrosis factor-α in the observation group were significantly lower than those in the control group (P < 0.05 or P < 0.001), but the levels of serum interleukin-10 and transforming growth factor-β in the observation group were significantly higher than those in the control group (P < 0.05 or P < 0.001). After treatment for 1 week, the percentages of CD3+CD4+T cell and CD4+CD25+Treg cells in the observation group were significantly higher than those in the control group (P < 0.001), but the percentages of CD3+CD8+ T cells and CD3-CD19+ B cells were significantly lower than those in the control group (P < 0.05 or P < 0.001). After treatment for 4 weeks, the percentages of CD3+ T cell ,CD3+CD4+ T cells and CD4+CD25+ Treg cells in the observation group were significantly higher than those in the control group (P < 0.05 or P < 0.001), but the percentages of CD3+CD8+ T cell and CD3-CD19+ B cells were significantly lower than those in the control group (P < 0.05 or P < 0.001). After treatment for 12 weeks, the MELD and Child-Pugh scores in the observation group were significantly lower than those in the control group (P < 0.05). During the follow-up period, none of the cases in the observation group developed liver failure, but five cases in the control group did. In addition, the incidence of complications and cumulative mortality in the observation group were significantly lower than those in the control group (P < 0.05). These results show that the human umbilical cord mesenchymal stem cell transplantation may alleviate liver inflammation and improve liver function, and then may reduce the incidence of hepatic failure and mortality for patients with decompensated cirrhosis due to hepatitis B.

     

     

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    Co-treatment of endothelial progenitor cells and pioglitazone improves kidney function in diabetic rats
    Wang Song, Zheng Xi-sheng, Wang Shan, Fang Fang
    2017, 21 (17):  2702-2707.  doi: 10.3969/j.issn.2095-4344.2017.17.013
    Abstract ( 340 )   PDF (4461KB) ( 204 )   Save

    BACKGROUND: Pioglitazone is a common hypoglycemic drug capable of improving proliferation and activation, and inhibiting apoptosis of endothelial progenitor cells (EPCs). We speculated that the combined use of pioglitazone and EPCs transplantation could have significant improving effects on hyperglycemia and kidney function after diabetes mellitus.
    OBJECTIVE: To investigate the improving effect of EPCs transplantation combined with pioglitazone treatment on the kidney function of diabetic rat models.
    METHODS: The 15 of 75 Wistar rats were randomly selected and served as normal control group (no treatment). Animal models of type 1 diabetes mellitus were made in the rest 60 rats through the intraperitoneal injection of 40 mg/kg streptozotocin for continuous 5 days. The human EPCs (labeled by CM-Dil) were recovered, cultured and preserved until transplantation. After 4 weeks of modeling, the 60 rat models were randomly divided into model group (PBS injection), pioglitazone group, EPCs transplantation group and combined treatment group, followed by tail vein injection of EPCs suspension and/or intragastric administration of 20 mg/kg pioglitazone for continuous 4 days. After 8 weeks of treatment, the levels of glucose, insulin and creatinine in serum, urea nitrogen and urine protein during 24 hours were determined. The number and distribution of EPCs labeled by CM-Dil were detected by fluorescence microscope, the apoptosis in kidney cells was tested by TUNEL method, and the kidney weight/body weight ratio in rats was calculated.
    RESULTS AND CONCLUSION: Compared with the model group, the blood glucose and serum creatinine levels and the urea nitrogen and urine protein concentrations during 24 hours were significantly decreased (P < 0.05), and the serum insulin level was significantly increased (P  < 0.05) in the pioglitazone and EPCs transplantation groups. These biochemical indexes in the combined treatment group were more significantly altered compared with the model group (P  < 0.01). The kidney weight to the body weight ratio was lowest in the combined treatment group and lower in the pioglitazone and EPCs transplantation groups followed by the model group (P < 0.05). The order of apoptotic kidney cells labeled by TUNEL was as follows: model group > pioglitazone group > EPCs transplantation group > combined treatment group (P < 0.05). To conclude, the EPCs transplantation combined with pioglitazone treatment can decrease the blood glucose and serum creatinine levels and urea nitrogen and urine protein concentrations, improve the serum insulin level, reduce cell apoptosis in the kidney, and remit the kidney dysfunction of diabetic rats to a certain extent.

     

     

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    Cultivation, identification and differentiation of neural stem cells
    Zhu Qiong, Hao Yue-juan, Gao Shun-ji, Chen Zhong, Liu Zheng, Xu Ya-li
    2017, 21 (17):  2708-2713.  doi: 10.3969/j.issn.2095-4344.2017.17.014
    Abstract ( 445 )   PDF (5360KB) ( 266 )   Save

    BACKGROUND: Neural stem cell transplantation is an emerging therapeutic option in the recovery of neural lesions and neurodegenerative diseases. Neural stem cell culture and differentiation lay a foundation for the further study.
    OBJECTIVE: To improve the techniques for the isolation, cultivation, differentiation and identification of neural  stem cells, and to explore the biological characteristics of cells. 
    METHODS: The neural stem cells from C57BL/6 fetal rats were isolated and cultured in vitro using neurophere culture method followed by morphological and ultrastucture examination. The growth curve and cell cycle of passage 3 cells were drawn and analyzed. Nestin expression was tested by immunofluorescence. Neural stem cells induced in 1% and 10% fetal bovine serum were identified using anti-GFAP, anti-βIII-tubulin and anti-MBP by immunofluorescence.
    RESULTS AND CONCLUSION: The neurospheres exhibited strong cell proliferation ability. Under transmission electron microscope, there was a high nuclear/cytoplasmic ratio in the neural stem cells, indicating a low differentiation degree. Immunofluorescence analysis revealed that neural stem cells were positive for Nestin. The induced cells were positive for GFAP, βIII-tubulin, and MBP, indicating these cells were induced to differentiate into astrocytes, neurons and oligodendrocytes, and there were more neurons in 1% fetal bovine serum than those in 10% fetal bovine serum. In conclusion, we could successfully isolate neural stem cells in C57BL/6 mice, and low concentration of fetal bovine serum contributes to more neurons differentiated from neural stem cells.

     

     

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    Comparison of three kinds of mesenchymal stem cells differentiating into nerve cells under co-culture induction
    Xu Li-li, Wang Hong-yuan, Li Xue-da, Liu Bing, Zheng Fang-fang, Yang Nai-long
    2017, 21 (17):  2714-2721.  doi: 10.3969/j.issn.2095-4344.2017.17.015
    Abstract ( 350 )   PDF (7061KB) ( 195 )   Save

    BACKGROUND: Scholars have been trying to create a microenvironment similar to the human body, which can induce the directional differentiation of mesenchymal stem cells from human bone marrow, placenta and umbilical cord blood.
    OBJECTIVE: To compare the neuronal differentiation of human bone marrow mesenchymal stem cells, human placental mesenchymal stem cells and human umbilical cord blood mesenchymal stem cells induced by co-culture with nerve cells.
    METHODS: Human bone marrow mesenchymal stem cells, human placental mesenchymal stem cells and human umbilical cord blood mesenchymal stem cells cultured in vitro were co-cultured with nerve cells using the Transwell system. The morphological changes of three kinds of cells in the co-culture system were detected. After co-culture for 4-5 days, immunofluorescence staining was used to measure the expression of neuron-specific enolase in cells. Mesenchymal stem cells only cultured in low glucose DMEM medium were used as controls.
    RESULTS AND CONCLUSION: These three kinds of mesenchymal stem cells were extended, and interconnected processes were detective. The positive expression of neuron-specific enolase was highest in the human umbilical cord blood mesenchymal stem cells followed by human placental mesenchymal stem cells and human bone marrow mesenchymal stem cells in order. In the control group, none of the three kinds of mesenchymal stem cells have neuronal morphology, and the expression of neuron specific enolase was negative for the immunofluorescence staining. To conclude, microenvironment provided by nerve cells can induce these three kinds of mesenchymal stem cells to differentiate into neurons.

     

     

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    Construction of seed cells with the stable expression of human bone morphogenetic protein 2 gene for bone tissue engineering
    Yu Li-min, Ma Jun-xuan, Li Ji-yun, Yu Bin-sheng
    2017, 21 (17):  2722-2728.  doi: 10.3969/j.issn.2095-4344.2017.17.016
    Abstract ( 279 )   PDF (5335KB) ( 203 )   Save

    BACKGROUND: Because of the non-homology of protein and gene between human and animals, to promote osteogenesis or spinal fusion of animals by construction of tissue-engineered bone with the human gene has influenced the experimental validation.
    OBJECTIVE: To construct the seed cell line for bone tissue engineering with stable expression of human bone morphogenetic protein 2 (hBMP2).
    METHODS: The full-length hBMP2 gene was cloned from human muscle tissues by nested RT-PCR and transfected to human bone marrow mesenchymal stem cells (hBMSCs) with lipidosome. The transfected hBMSCs were cultured with G418 in vitro to screen and purify the cells. A series of analyses such as RT-PCR, dot-ELISA, immunohistochemstry and alkaline phosphatase activity analysis were performed to evaluate the situation of hBMP2 expression and secretion at 48 hours and 3 weeks after the transduction. hBMSCs transduced with empty plasmid and the normal hBMSCs served as positive control and blank control groups, respectively, which were used for observation of cell growth, proliferation and biological characteristics of transfected cells.
    RESULTS AND CONCLUSION: The transfected hBMSCs appeared in small groups or clusters, and had a good proliferation after subculture in vitro. Some G418-resistance cell clones and calcium nodules were found when cultured with G418 in vitro. No significant difference was noted in the cell proliferation between the hBMP2 transfection group and two control groups. The ALP activity in the hBMP2 transfection group remained significantly higher than that in the two control groups (P < 0.01). At 48 hours and 3 weeks after transduction, hBMSCs could express actively hBMP2 by RT-PCR monitoring, and had a positive reaction of dot-ELISA and immunohistochemical analysis. The expression of hBMP2 gene in the experiment group at 48 hours was significantly higher than that at 3 weeks after transduction while there was no expression of hBMP2 gene in the two control groups. The above results show that the hBMSCs transfected by hBMP2 gene not only have potentials of normal proliferation and osteogenic differentiation, but also can stably express hBMP2.

     

     

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    Three methods to isolate osteoblasts: stem cell induction, cell line induction and primary isolation
    Deng Xiang-yu, Chen Sheng, Shao Zeng-wu, Zheng Dong
    2017, 21 (17):  2729-2934.  doi: 10.3969/j.issn.2095-4344.2017.17.017
    Abstract ( 404 )   PDF (4817KB) ( 209 )   Save

    BACKGROUND: Osteoblasts have become a kind of important seed cells in bone tissue engineering. However, it is difficult to harvest osteoblasts, and the purity and calcification ability of osteoblasts isolated by different methods are inconsistent.
    OBJECTIVE: To compare the purity and calcification ability of osteoblasts induced from mouse bone marrow mesenchymal stem cells, MC3T3 cell lines, and cultured primarily from the neonatal mouse cranium.
    METHODS: Mouse bone marrow mesenchymal stem cells were isolated by differential adhesion method, and after passaing, passage 3 cells were cultured in osteogenic induction medium for 21 days. MC3T3 cell lines were cultured in osteogenic induction media 1 and 2 for 21 days. Osteoblasts were cultured primarily from neonatal mouse cranium by type I collagenase digestion method. Calcium nodules of osteoblasts obtained by three methods were observed by Alizarin red staining to detect osteogenic activity of cells.
    RESULTS AND CONCLUSION: (1) There were average 16.3 calcium nodules per low-power field after osteogenic induction of bone marrow mesenchymal stem cells. (2) There were sparsely distributed calcium nodules in MC3T3 cells after induction with osteogenic induction medium 1, accounting for 1.7 calcium nodules per low-power field, while there were dense calcium nodules in MC3T3 cells after induction with osteogenic induction medium 2, accounting for 44.6 calcium nodules per low-power field. There was a significant difference in the calcium nodule formation ability between the two groups (P < 0.01). (3) After primary culture, there was only 0.6 calcium nodule per low-power field. (4) Except for the insignificant difference between osteogenic induction medium 1 and primary culture groups, there were significant differences in pair-wise comparison of any other two groups. Except the insignificant difference between group I of MC3T3 inducing conditional media and primary culture osteoblasts, there were significant differences in the osteogenic ability between groups (P < 0.01). In conclusion, it is a better method to culture MC3T3 cells in osteogenic induction medium 2 containing dexamethasone, because many uncontrollable factors are involved in the isolation and culture of bone marrow mesenchymal stem cells.

     

     

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    Salvianolic acid B effects on the proliferation, differentiation and apoptosis of hippocampal neural stem cells in rats following oxygen-glucose deprivation
    Li Du-fang, Miao Ling-juan, Li Ning, Liang He, Ren De-qi, Guo Jian
    2017, 21 (17):  2735-2740.  doi: 10.3969/j.issn.2095-4344.2017.17.018
    Abstract ( 276 )   PDF (4448KB) ( 212 )   Save

    BACKGROUND: Salvianolic acid B can ease nerve injury and promote neurogenesis, but its effects on proliferation, apoptosis and differentiation of neural stem cells in the hippocampus remain unclear.
    OBJECTIVE: To study the effects of salvianolic acid B on proliferation, apoptosis and differentiation of rat hippocampal neural stem cells following oxygen-glucose deprivation.
    METHODS: Hippocampal neural stem cells were isolated from newborn Sprague-Dawley rats, and divided into six groups, five of which were cultured in an incubator containing anaerobic mixtures (1% O2, 5% CO2 and 94% N2) for 150 minutes followed by treatment with different concentrations of salvianolic acid B (0, 5, 10, 20, 40 mg/L), respectively. After 4 days of intervention, MTT was used to detect cell proliferation. After 48 hours of intervention, flow cytometry was used to detect cell apoptosis in the hippocampus. After 5 days of culture, flow cytometry was performed to evaluate the percentage of cells positive for neuron-specific enolase and glial fibrillary acidic protein. Normally cultured cells acted as controls (normoxic group).
    RESULTS AND CONCLUSION: Compared with the normoxic group, the proliferation of neural stem cells was decreased significantly (P < 0.01) and the rate of apoptosis was increased in the oxygen-glucose deprivation group (P < 0.01). After treatment with different concentrations of salvianolic acid B, the cell viability and the ratio of neurons in total cells were increased, and the ratio of astrocytes was decreased, especially in 20 and 40 mg/L groups (P < 0.01). In conclusion, these results suggest that salvianolic acid B alleviates adverse effects of oxygen-glucose deprivation on neural stem cell proliferation, differentiation and apoptosis.

     

     

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    Expression of OCT4 and SOX2 in esophageal squamous cell carcinoma and its relationship with clinical prognosis
    Wen Zi-hai, Lv Qiao-yun, Li Xiao-hua
    2017, 21 (17):  2741-2745.  doi: 10.3969/j.issn.2095-4344.2017.17.019
    Abstract ( 285 )   PDF (1075KB) ( 314 )   Save

    BACKGROUND: Studies have shown that OCT4, SOX2 and HIWI can express in tumor tissues.
    OBJECTIVE: To investigate the relationship between the expression of stem cell transcription factors SOX2 and OCT4 in esophageal squamous cell carcinoma and their clinical characteristics and prognosis.
    METHODS: Expression levels of SOX2 and Oct4 were detected using immunohistochemical SP method in 77 cases of esophageal squamous cell carcinoma and 40 cases of adjacent cancer tissues confirmed by pathological examination, and then the their relationship with prognosis and clinical characteristics of the patients was analyzed.
    RESULTS AND CONCLUSION: Significantly higher levels of SOX2 and Oct4 were found in the esophageal cancer tissues than the adjacent cancer tissues (P < 0.05). SOX2 and Oct4 were highly expressed in the esophageal cancer tissues isolated from poorly differentiated, lymph node metastasis patients (P < 0.05). During the 2-year follow-up, the median survival of patients positive for SOX2 and Oct4 was only 24 and 21 months, respectively, which was significantly lower than that of negative patients (30 and 33 months, respectively). These findings indicate that the highly expressed SOX2 and Oct4 in esophageal cancer tissues are associated with the differentiation, metastasis and prognosis of the patients with esophageal squamous cell carcinoma.

     

     

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    Bone marrow mesenchymal stem cells: aging features and relevant treatments
    Chen Yu-hao, Zhu Xiang-qing, Pan Xing-hua
    2017, 21 (17):  2746-2752.  doi: 10.3969/j.issn.2095-4344.2017.17.020
    Abstract ( 465 )   PDF (1002KB) ( 315 )   Save

    BACKGROUND: Bone marrow mesenchymal stem cells may be sensitive to age-related diseases, which is a contributory factor of bone remodeling after degenerative diseases.
    OBJECTIVE: To summarize the features of aging and progress in treatments related to cell aging.
    METHODS: We retrieved PubMed database for articles concerning aging of bone marrow mesenchymal stem cells and its treatments published from June 2006 to June 2016. The key words were “MSCs, aging”. Finally, 61 relevant articles were selected and reviewed in reference with Hazzard’s Geriatric Medicine and Gerontology.
    RESULTS AND CONCLUSION: Bone marrow derived mesenchymal stem cells can support the growth of hematopoietic progenitor cells in the immune and hematopoietic system, promote repair of the bone marrow, and influence bone growth and remodeling. However, cell aging occurs with age and other factors will affect cell function. Aging bone marrow mesenchymal stem cells show shortened telomere, reduced proliferation and differentiation ability and increased oxidative stress level. Current evidence has confirmed that cell aging can be delayed or prevented by adjustment of age-related telomerase activities, oxidative stress intervention, Wnt/beta-catenin signaling pathway in the microenvironment, regulation of p16, p53 gene expression or drugs such as histone acetyltransferase and lysophosphatidic acid, thereby to improve the clinical curative effect of bone marrow mesenchymal stem cells. However, the exact mechanism remains to be further studied.

     

     

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    Role of epithelial-mesenchymal transition in stem cell differentiation and tumorigenesis
    Zhang Feng-bo, Li Ling-li, Jiang Xin-xing, Ma Yan-Lin, Li Qi
    2017, 21 (17):  2753-2758.  doi: 10.3969/j.issn.2095-4344.2017.17.021
    Abstract ( 306 )   PDF (916KB) ( 225 )   Save

    BACKGROUND: Epithelial-mesenchymal transition is closely related to embryonic development, stem cell-induced differentiation, injury tissue repair and tumorigenesis.
    OBJECTIVE: To review the role of epithelial-mesenchymal transition in stem cell differentiation and tumorigenesis.
    METHODS: The CNKI and PubMed databases were retrieved by computer for relevant literatures published from 2001 to 2016 with the key words of “epithelial-mesenchymal transition, stem cell, tumor/cancer” in Chinese and English, respectively. 1 249 articles were retrieved in total, and 50 papers were suitable for final analysis.
    RESULTS AND CONCLUSION: The epithelial-mesenchymal transition is closely associated with stem cell differentiation, tumorigenesis and tumor progression. The emergence of epithelial-mesenchymal transition related markers were found in stem cell differentiation and tumor invasion and metastasis. Epithelial-mesenchymal transition is affected by a variety of regulatory factors, and the differentiation of stem cells and the occurrence and development of tumor are also multi-procedural and multi-step complex processes. Although we have a more thorough understanding on occurrence mechanisms and some regulation mechanisms of epithelial-mesenchymal transition for stem cell differentiation and tumorigenesis, the understanding of the complex regulatory network is still not enough. How to have a deeper understanding of the occurrence and regulation mechanisms of epithelial-mesenchymal transition, and how to apply research results safely and effectively in the clinical prevention, diagnosis and treatment will be the common goal of us now and in the future.

     

     

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    Factors regulating the adipo-osteogenic differentiation of bone marrow mesenchymal stem cells
    Zhou Xin, Zhao Jia-jia, Chen Li-li
    2017, 21 (17):  2759-2765.  doi: 10.3969/j.issn.2095-4344.2017.17.022
    Abstract ( 270 )   PDF (938KB) ( 248 )   Save

    BACKGROUND: Bone marrow mesenchymal stem cells (BMSCs) with multiple differentiation potential can be induced into osteogenic or adipogenic differentiation under certain conditions.
    OBJECTIVE: To review the related factors regulating the adipo-osteogenic differentiation of BMSCs.
    METHODS: A computer-based search of CNKI and PubMed databases was performed for literature concerning the related factors regulating the adipo-osteogenic differentiation of BMSCs published from January 2006 to August 2016. The search terms were “bone marrow mesenchymal stem cells, osteogenic differentiation, adipocyte differentiation” in Chinese and English, respectively.
    RESULTS AND CONCLUSION: Signaling pathways, transcription factors, and small molecule compounds that are interacted are key factors in the regulation of BMSCs differentiation, so the techniques to intervene BMSCs differentiation based on these key molecules may correct bone or fat abnormality and can be applied to tissue engineering and regenerative medicine in the future. Additionally, the biological clock is also one of the most important factors for adipo-osteogenic differentiation of BMSCs by regulating signaling pathways or transcription factors. 

     

     

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    Mesenchymal stem cells in the treatment of myocardial infarction: how long is the way from bench to bedside?
    Zhao Qi-ming, Sheng Kai, Zhang Xuan-fen
    2017, 21 (17):  2766-2775.  doi: 10.3969/j.issn.2095-4344.2017.17.023
    Abstract ( 579 )   PDF (1305KB) ( 314 )   Save

    BACKGROUND: Mesenchymal stem cells, a kind of popular seed cells for cell transplantation after myocardial injury, have become a hot research topic in the treatment of ischemic heart diseases.
    OBJECTIVE: To review the new progress of mesenchymal stem cell transplantation in the treatment of ischemic heart diseases.
    METHODS: We searched Medline, Ovid Embase, PubMed Central, Cochrane Library, Chinese Periodical Full-Text Database, Chinese Biomedical Literature Database, VIP database, Wanfang Database for relevant articles in Chinese and English languages, and the retrieval time was from 1985 to 2015. Articles related to randomized controlled trials or clinical research on mesechymal stem cell transplantation for treatment of ischemic heart diseases were included, and relevant review were also included. Observational studies, case reports, study protocols with no standard or rational design, reviews with no normative and rigorous inclusion criteria, cross-test studies, cluster randomized trials, and studies that have nothing to do with the topic were excluded.
    RESULTS AND CONCLUSION: Through literature screening, we summarize the research progress in the mesenchymal stem cell transplantation, including cell source, safety, efficacy, action of mechanism and injection mode, and analyze the merits and demerits of mesenchymal stem cell transplantation. Bone marrow mesenchymal stem cell transplantation provides a new insight into the clinical treatment of myocardial infarction, but there are still many problems to be solved, such as cell quality, cell dose, transplantation mode, transplantation timing and patient selection, which so limit the clinical application of mesenchymal stem cell transplantation.

     

     

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    The immunomodulatory function and clinical applications of mesenchymal stem cells
    Yang Yan-mei, Jiang Xiao-xia, Wen Ning
    2017, 21 (17):  2776-2782.  doi: 10.3969/j.issn.2095-4344.2017.17.024
    Abstract ( 439 )   PDF (1633KB) ( 300 )   Save

    BACKGROUND: Mesenchymal stem cells (MSCs) have the abilities of self-renewal, multidirectional differentiation and immunomodulation, and have become the focus of current research.
    OBJECTIVE: To summarize the immunomodulation of MSCs to different immune cells and the clinical applications of MSCs in the treatment of immune-related diseases.
    METHODS: The first author searched the PubMed and the CKNI databases for relative articles from January 1974 to December 2016. The key words were “mesenchymal stem cells, immunomodulation, MSC1 and MSC2, autoimmune diseases” in English and Chinese, respectively. Finally, 52 representative articles were included.
    RESULTS AND CONCLUSION: MSCs can inhibit the function of T lymphocytes, reduce the activation, proliferation and antibody secretion of B lymphocytes, affect the polarization of macrophages, inhibit the maturation of dendritic cells, inhibit the proliferation and toxicity of NK cells, so MSCs have the great potential in the treatment of immune-related diseases. However, MSCs exhibit the opposite immunomodulatory abilities under different inflammatory microenvironments, and moreover the definite and controllable mechanism of this phenomenon is still unclear, Therefore, future investigations may focus on the specific mechanism of MSCs in the clinical treatment of immune-related diseases.

     

     

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    Current status of research on separation methods of graft-versus-leukemia effect and graft-versus-host disease after allogeneic hematopoietic stem cell transplantation 
    Wang Bing-chen, Jiang Ming
    2017, 21 (17):  2783-2788.  doi: 10.3969/j.issn.2095-4344.2017.17.025
    Abstract ( 279 )   PDF (853KB) ( 202 )   Save

    BACKGROUND: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the essence of immune cell transplantation, its curative effect mainly depends on graft-versus-leukemia (GVL) effect, but its accompanying graft-versus-host disease (GVHD) can increase mortality and affect the therapeutic efficacy. Until now, researchers have proposed a variety of ways to reduce GVHD but enhance or maintain GVL. However, these methods have their own advantages, disadvantages and controversial points. So their relationship and separation methods still need further studies.
    OBJECTIVE: To summarize the current status of research about separation methods of GVHD and GVL after allo-HSCT.
    METHODS: Using “hematopoietic stem cell transplantation, graft versus leukemia, graft-versus-host disease, donor lymphocyte infusion, regulatory T cell, natural killer cell, mesenchymal stem cell” as key words, we retrieved Wanfang, CNKI and PubMed databases (2000-2016) by computer.
    RESULTS AND CONCLUSION: We finally reviewed 41 literatures about enhancing GVL and reducing GVHD in recent years. At present, the relationship between GVHD and GVL, and their respective mechanisms are still unclear. There are many methods to separate GVHD and GVL, but these methods have their own advantages and disadvantages. The best solution has not yet been unified, and still needs further study.

     

     

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