[1]曹芳,张焕婷,刘强,等.50 Hz 1 mT脉冲电磁场对脐带间充质干细胞免疫调节能力的影响及其安全性评价[J].国际放射医学核医学杂志,2017,41(2):113-120.[doi:10.3760/cma.j.issn.1673-4114.2017.02.007]
 Cao Fang,Zhang Huanting,Du Liqing,et al.Effect and safety evaluation of 50-Hz 1-mT pulsed electromagnetic field on the immunomodulation of human umbilical cord mesenchymal stem cells[J].International Journal of Radiation Medicine and Nuclear Medicine,2017,41(2):113-120.[doi:10.3760/cma.j.issn.1673-4114.2017.02.007]
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50 Hz 1 mT脉冲电磁场对脐带间充质干细胞免疫调节能力的影响及其安全性评价(/HTML)
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《国际放射医学核医学杂志》[ISSN:1673-4114/CN:12-1381/R]

卷:
41
期数:
2017年第2期
页码:
113-120
栏目:
论著
出版日期:
2017-03-25

文章信息/Info

Title:
Effect and safety evaluation of 50-Hz 1-mT pulsed electromagnetic field on the immunomodulation of human umbilical cord mesenchymal stem cells
作者:
曹芳1 张焕婷1 刘强2 杜利清2 曹晓沧1
1. 300052 天津, 天津医科大学总医院消化内科;
2. 300192 天津, 北京协和医学院中国医学科学院放射医学研究所, 天津市放射医学与分子核医学重点实验室
Author(s):
Cao Fang1 Zhang Huanting1 Du Liqing2 Liu Qiang2 Cao Xiaocang1
1. Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin 300052, China;
2. Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences, Peking Union Medical College, Tianjin 300192, China
关键词:
间质干细胞辐射脉冲电磁场免疫调节
Keywords:
Mesenchymal stem cellRadiationPulsed electromagnetic fieldImmunomodulation
DOI:
10.3760/cma.j.issn.1673-4114.2017.02.007
摘要:
目的 探讨50 Hz 1 mT脉冲电磁场(PEMF)对脐带间充质干细胞(MSC)免疫调节能力的影响及其安全性。方法 采用50 Hz 1 mT PEMF辐照脐带MSC,MTT法检测辐照后细胞活性的变化;实时荧光定量PCR法检测脐带MSC的环氧合酶2(COX2)、IL-10、吲哚胺-2,3-双加氧酶(IDO)、肝细胞生长因子(HGF)和转化生长因子β(TGF-β)等基因mRNA表达水平的改变;流式细胞仪检测PEMF对脐带MSC活性氧(ROS)水平、细胞凋亡和细胞周期的影响;单细胞凝胶电泳分析脐带MSC DNA损伤的情况。采用SPSS19.0软件,对各组间数据进行独立样本t检验分析。结果 50 Hz 1 mT PEMF辐照可增强脐带MSC的细胞活性,其中每天辐照4 h组变化最为明显,差异有统计学意义(t=3.505,P<0.05)。PEMF辐照可促进COX2、HGF、IDO和TGF-β等免疫调节因子mRNA的表达,但变化不明显,差异无统计学意义(t=0.982~2.376,均P>0.05),对于干扰素γ(IFN-γ)激活的MSC,PEMF辐照可显著上调COX2、HGF、IDO和TGF-β的mRNA表达水平,差异有统计学意义(t=2.436~3.747,均P<0.05)。50 Hz 1 mT PEMF辐照对脐带MSC的ROS水平、DNA损伤及细胞凋亡率、细胞周期无显著影响。结论 对于IFN-γ激活的MSC,50 Hz 1 mT PEMF可显著上调COX2、HGF、IDO和TGF-β的mRNA表达水平,从而增强脐带MSC的免疫调节能力。50 Hz 1 mT PEMF对脐带MSC的ROS水平、细胞凋亡及DNA损伤无明显影响,此参数下的PEMF辐照对脐带MSC是安全的。
Abstract:
Objective To investigate the effect of 50-Hz, 1-mT pulsed electromagnetic field (PEMF) on the immunomodulation of human umbilical cord mesenchymal stem cells(MSCs) and to evaluate the safety of PEMF as a therapeutic strategy. Methods Changes in cell viability was observed via MTT. Real-time PCR was used to detect the expression levels of cyclooxygenase 2(COX2), indoleamine 2,3-dioxygenase(IDO), IL-10, hepatocyte growth factor(HGF), and transforming growth factor-β(TGF-β) in MSCs. To explore the safety of PEMF, a flow cytometry experiment was conducted to observe apoptosis and reactive oxygen species(ROS) level. DNA damage was detected via comet assay. Data were statistically analyzed via t-test with SPSS 19.0. P<0.05 was considered statistically significant. Results Cell viability increased, with the most obvious increase in 4 h/d(t=3.505, P<0.05). In interferon-γ(INF-γ)-activated MSC, the expression levels of immunomodulation factors improved after PEMF irradiation(t=2.436-3.747, all P<0.05). Furthermore, PEMF did not induce cell apoptosis, ROS generation, and DNA damage. Conclusion 50-Hz, 1-mT PEMF improves MSC immunomodulation and may not cause radiation injury.

参考文献/References:

[1] Friedenstein AJ, Gorskaja JF, Kulagina NN. Fibroblast precursors in normal and irradiated mouse hematopoietic organs[J]. Exp Hematol, 1976, 4(5):267-274.
[2] Chamberlain G, Fox J, Ashton B, et al. Concise review:mesenchymal stem cells:their phenotype, differentiation capacity, immunological features, and potential for homing[J]. Stem Cells, 2007, 25(11):2739-2749. DOI:10. 1634/stemcells. 2007-0197.
[3] Munir H, McGettrick HM. Mesenchymal stem cell therapy for autoimmune disease:risks and rewards[J]. Stem Cells Dev, 2015, 24(18):2091-2100. DOI:10. 1089/scd. 2015. 0008.
[4] Cras A, Farge D, Carmoi T, et al. Update on mesenchymal stem cell-based therapy in lupus and scleroderma[J/OL]. Arthritis Res Ther, 2015, 17:301[2017-01-09]. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4631077. DOI:10.1186/s13075-015-0819-7.
[5] Furlani D, Ugurlucan M, Ong L, et al. Is the intravascular administration of mesenchymal stem cells safe? Mesenchymal stem cells and intravital microscopy[J]. Microvasc Res, 2009, 77(3):370-376. DOI:10. 1016/j. mvr. 2009. 02. 001.
[6] Ferroni L, Tocco I, De Pieri A, et al. Pulsed magnetic therapy increases osteogenic differentiation of mesenchymal stem cells only if they are pre-committed[J/OL]. Life Sci, 2016, 152:44-51[2017-01-09]. http://www.sciencedirect.com/science/article/pii/S0024320516301709. DOI:10. 1016/j. lfs. 2016. 03. 020.
[7] Boyette MY, Herrera-Soto JA. Treatment of delayed and nonunited fractures and osteotomies with pulsed electromagnetic field in children and adolescents[J/OL]. Orthopedics, 2012, 35(7):e1051-e1055[2017-01-09]. http://m2.wyanokecdn.com/868f60c9e861-91479086696703af8552.pdf. DOI:10.3928/01477447-20120621-20.
[8] Saliev T, Mustapova Z, Kulsharova G, et al. Therapeutic potential of electromagnetic fields for tissue engineering and wound healing[J]. Cell Prolif, 2014, 47(6):485-493. DOI:10. 1111/cpr. 12142.
[9] Fu YC, Lin CC, Chang JK, et al. A novel single pulsed electromagnetic field stimulates osteogenesis of bone marrow mesenchymal stem cells and bone repair[J/OL]. PLoS One, 2014, 9(3):e91581[2017-01-09]. http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0091581. DOI:10. 1371/journal. pone. 0091581.
[10] Negm A, Lorbergs A, Macintyre NJ. Efficacy of low frequency pulsed subsensory threshold electrical stimulation vs placebo on pain and physical function in People with knee osteoarthritis:systematic review with meta-analysis[J]. Osteoarthritis Cartilage, 2013, 21(9):1281-1289. DOI:10. 1016/j. joca. 2013. 06. 015.
[11] Abbruzzese L, Iacopi E, Coppelli A, et al. Safety and effectiveness of therapeutic magnetic resonance in the management of postsurgical lesion of the diabetic foot[J]. Int J Low Extrem Wounds, 2015, 14(1):4-10. DOI:10. 1177/1534734614568374.
[12] Shen Y, Cao X, Tan T, et al. 10-Hz repetitive transcranial magnetic stimulation of the left dorsolateral prefrontal cortex reduces heroin cue craving in long-term addicts[J/OL]. Biol Psychiatry, 2016, 80(3):e13-e14[2017-01-09]. https://linkinghub.elsevier.com/retrieve/pii/S0006-3223(16)00093-7. DOI:10. 1016/j. biopsych. 2016. 02. 006.
[13] Wang J, Tang N, Xiao Q, et al. Pulsed electromagnetic field May accelerate in vitro endochondral ossification[J]. Bioelectromagnetics, 2015, 36(1):35-44. DOI:10. 1002/bem. 21882.
[14] Kim HJ, Jung J, Park JH, et al. Extremely low-frequency electromagnetic fields induce neural differentiation in bone marrow derived mesenchymal stem cells[J]. Exp Biol Med, 2013, 238(8):923-931. DOI:10. 1177/1535370213497173.
[15] Shu J, He X, Zhang L, et al. Human amnion mesenchymal cells inhibit lipopolysaccharide-induced TNF-α and IL-1β production in THP-1 cells[J/OL]. Biol Res, 2015, 48:69[2017-01-09]. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4690291. DOI:10. 1186/s40659-015-0062-3.
[16] Wolf FI, Torsello A, Tedesco B, et al. 50-Hz extremely low frequency electromagnetic fields enhance cell proliferation and DNA damage:possible involvement of a redox mechanism[J]. Biochim Biophys Acta, 2005, 1743(1-2):120-129. DOI:10. 1016/j. bbamcr. 2004. 09. 005.
[17] Yagi H, Soto-Gutierrez A, Parekkadan B, et al. Mesenchymal stem cells:Mechanisms of immunomodulation and homing[J]. Cell Transplant, 2010, 19(6):667-679. DOI:10. 3727/096368910X508762.
[18] Spaggiari GM, Abdelrazik H, Becchetti F, et al. MSCs inhibit monocyte-derived DC maturation and function by selectively interfering with the generation of immature DCs:central role of MSC-derived prostaglandin E2[J]. Blood, 2009, 113(26):6576-6583. DOI:10. 1182/blood-2009-02-203943.
[19] Spaggiari GM, Capobianco A, Abdelrazik H, et al. Mesenchymal stem cells inhibit natural killer-cell proliferation, cytotoxicity, and cytokine production:role of indoleamine 2, 3-dioxygenase and prostaglandin E2[J]. Blood, 2008, 111(3):1327-1333. DOI:10. 1182/blood-2007-02-074997.
[20] Meisel R, Brockers S, Heseler K, et al. Human but not murine multipotent mesenchymal stromal cells exhibit broad-spectrum antimicrobial effector function mediated by indoleamine 2, 3-dioxygenase[J]. Leukemia, 2011, 25(4):648-654. DOI:10. 1038/leu. 2010. 310.
[21] Nauta AJ, Fibbe WE. Immunomodulatory properties of mesenchymal stromal cells[J]. Blood, 2007, 110(10):3499-3506. DOI:10. 1182/blood-2007-02-069716.
[22] Hsu WT, Lin CH, Chiang BL, et al. Prostaglandin E2 potentiates mesenchymal stem cell-induced IL-10+IFN-γ+CD4+ regulatory T cells to control transplant arteriosclerosis[J]. J Immunol, 2013, 190(5):2372-2380. DOI:10. 4049/jimmunol. 1202996.
[23] Selmani Z, Naji A, Zidi I, et al. Human leukocyte antigen-G5 secretion by human mesenchymal stem cells is required to suppress T lymphocyte and natural killer function and to induce CD4+CD25highFOXP3+ regulatory T cells[J]. Stem Cells, 2008, 26(1):212-222. DOI:10. 1634/stemcells. 2007-0554.
[24] Brown JM, Nemeth K, Kushnir-Sukhov NM, et al. Bone marrow stromal cells inhibit mast cell function via a COX2-dependent mechanism[J]. Clin Exp Allergy, 2011, 41(4):526-534. DOI:10. 1111/j. 1365-2222. 2010. 03685. x.
[25] Kim HS, Yun JW, Shin TH, et al. Human umbilical cord blood mesenchymal stem cell-derived PGE2 and TGF-β1 alleviate atopic dermatitis by reducing mast cell degranulation[J]. Stem Cells, 2015, 33(4):1254-1266. DOI:10. 1002/stem. 1913.
[26] Jian W, Wei Z, Zhiqiang C, et al. X-ray-induced apoptosis of BEL-7402 cell line enhanced by extremely low frequency electromagnetic field in vitro[J]. Bioelectromagnetics, 2009, 30(2):163-165. DOI:10. 1002/bem. 20461.
[27] Song MY, Yu JZ, Zhao DM, et al. The time-dependent manner of sinusoidal electromagnetic fields on rat bone marrow mesenchymal stem cells proliferation, differentiation, and mineralization[J]. Cell Biochem Biophys, 2014, 69(1):47-54. DOI:10. 1007/s12013-013-9764-8.

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备注/Memo

备注/Memo:
收稿日期:2017-01-09。
基金项目:国家自然科学基金(31670859);协和青年基金和中央高校基本科研业务费专项资金(3332016100);中国医学科学院&北京协和医学院中央级公益性科研院所基本科研业务费(2016ZX310198,2016RC310019);中国医学科学院放射医学研究所创新团队基金(1605)
通讯作者:曹晓沧,Email:doccaoxc@163.com
更新日期/Last Update: 2017-04-24