[1]王希莲,杨丽媛,粘红,等.人脐带间充质干细胞对兔自身免疫性干眼的疗效研究[J].眼科新进展,2017,37(1):019-23.[doi:10.13389/j.cnki.rao.2017.0005]
　WANG Xi-Lian,YANG Li-Yuan,NIAN Hong,et al.Treatment effect of mesenchymal stem cells on rabbit autoimmune dry eye[J].Recent Advances in Ophthalmology,2017,37(1):019-23.[doi:10.13389/j.cnki.rao.2017.0005]
点击复制

人脐带间充质干细胞对兔自身免疫性干眼的疗效研究/HTML
分享到：

《眼科新进展》[ISSN:1003-5141/CN:41-1105/R]

卷:
37卷
期数:
2017年1期
页码:
019-23
栏目:
实验研究
出版日期:
2017-01-05

文章信息/Info

Title:
Treatment effect of mesenchymal stem cells on rabbit autoimmune dry eye
作者:
王希莲; 杨丽媛; 粘红; 路晓晓; 李雪; 刘勋; 魏瑞华
300400　天津市，天津北辰医院眼科(王希莲)；300384　天津市，天津医科大学眼科医院，天津医科大学眼科研究所（杨丽媛，粘红，路晓晓，李雪，刘勋，魏瑞华）
Author(s):
WANG Xi-Lian; YANG Li-Yuan; NIAN Hong; LU Xiao-Xiao; LI Xue; LIU Xun; WEI Rui-Hua
Department of Ophthalmology,Beichen Hospital of Tianjin （WANG Xi-Lian），Tianjin 300400，China;the Eye Hospital of Tianjin Medical University，Tianjin Medical University Eye Institute（YANG Li-Yuan，NIAN Hong，LU Xiao-Xiao，LI Xue，LIU Xun，WEI Rui-Hua），Tianjin 300384，China
关键词:
间充质干细胞; 兔自身免疫性干眼; 细胞因子; 白细胞介素-10
Keywords:
mesenchymal stem cells; rabbit autoimmune dry eye; cytokines; interleukin-10
分类号:
R777
DOI:
10.13389/j.cnki.rao.2017.0005
文献标志码:
A
摘要:
目的　通过建立稳定的兔自身免疫性干眼模型，观察人脐带来源的间充质干细胞（human umbilical cord mesenchymal stem cells，hUC-MSCs)对自身免疫性干眼的作用并初步探讨其机制。方法　体外分离、培养hUC-MSCs并对其进行鉴定；采用静脉回输自体激活的淋巴细胞建立兔自身免疫性干眼模型，将兔分为正常对照组、干眼模型组和hUC-MSCs治疗组，hUC-MSCs治疗组于回输淋巴细胞后输注1 mL 1×107个·mL-1 hUC-MSCs，连续输注5 d，对照组输注等体积的PBS。三组分别在术后2周、4周、6周检测泪液分泌量、泪膜破裂时间和角膜荧光素钠染色，6周后行组织病理学观察，并检测泪腺组织中细胞因子的表达水平。结果　术后2周、4周、6周hUC-MSCs治疗组较干眼模型组泪液分泌量、泪膜破裂时间显著升高(均为P<0.05)；角膜荧光素钠染色着色显著减轻，组织病理学观察泪腺组织淋巴细胞浸润较干眼模型组显著减少。hUC-MSCs治疗组和干眼模型组相比，泪腺组织中炎性因子IFN-γ、IL-17表达显著降低（F=50.48、18.13；均为P<0.05)，而抑炎因子IL-10、TGF-β的表达显著升高（F=31.06、21.40；均为P<0.05)。结论　hUC-MSCs减轻兔自身免疫性干眼，对其发挥免疫调控作用。
Abstract:
Objective　To observe the effects of human umbilical cord derived mesenchymal stem cells（hUC-MSCs） on autoimmune dry eye,and explore the mechanism of the human umbilical cord derived mesenchymal stem cells.Methods　The isolation and culture of human umbilical cord derived mesenchymal stem cells in vitro,and then identified;The autologous activated lymphocytes through vein was used to establish autoimmune dry eye rabbit model,and divided into normal control group,dry eye model group,and mesenchymal stem cell treatment group.The mesenchymal stem cells (1×107cell·mL-1,1 mL) were infused in the treatment group after reinfusion of lymphocyte for 5 days,the control groups were infused with equal volume of PBS.In the three groups,tear secretion and tear film stability and corneal fluorescein staining were detected at 2 weeks,4 weeks and 6 weeks,histological observation was performed at 6 weeks,and the expression of cytokines in lacrimal gland tissue was detected.Results　The tear secretion,tear break-up time in the treatment group were higher than those in the model group (all P<0.05),corneal fluorescein staining was reduced,and the lymphocytes infiltration was obviously decreased.Compared with model group,the expression of IFN-gamma and IL-17 in the lacrimal gland tissue of treatment group were obviously decreased (F=50.48,18.13;all P<0.05),but the expression of IL-10 and TGF-beta were increased (F=31.06,21.40;all P<0.05).Conclusion　The mesenchymal stem cells derived from human umbilical cord blood stem cells can reduce their own immune dry eye,and play the role of immune regulation.

参考文献/References:

［1］　VOULGARELIS M，TZIOUFAS AG.Pathogenetic mechanisms in the initiation and perpetuation of Sjogren’s syndrome［J］.Nat Rev Rheumatol，2010，6(9):529-537.
［2］　NGUYEN CQ，PECK AB.Unraveling the pathophysiology of Sjogren syndrome-associated dry eye disease［J］.Ocul Surf，2009，7(1):11-27.
［3］　FOXR I.Sjogren’s syndrome［J］.Lancet，2005，366(9482):321-331.
［4］　MESSMER EM.The pathophysiology，diagnosis，and treatment of dry eye disease［J］.Dtsch Arztebl Int，2015，112(5):71-82.
［5］　YAGCI A，GURDAL C.The role and treatment of inflammation in dry eye disease［J］.Int Ophthalmol，2014，34(6):1291-1301.
［6］　CHAMBERLAIN G，FOX J，ASHTON B，MIDDLETON J.Concise review:mesenchymal stem cells:their phenotype，differentiation capacity，immunological features，and potential for homing［J］.Stem Cells，2007，25(11):2739-2749.
［7］　DE MIGUEl MP，FUENTES-JULIAN S，BLAZQUEZ-MARTINEZ A，PASCUAl CY，ALLER MA，ARIAS J.Immunosuppressive properties of mesenchymal stem cells:advances and applications［J］.Curr Mol Med，2012，12(5):574-591.
［8］　GLENN JD，WHARTENBY KA.Mesenchymal stem cells:Emerging mechanisms of immunomodulation and therapy［J］.World J Stem Cells，2014，6(5):526-539.
［9］　WEI RH，THOMAS PB，SAMANT DM，SCHECHTER JE，MIRCHEFF AK，TROUSDALE MD.Autoimmune dacryoadenitis and sialadenitis induced in rabbits by intravenous injection of autologous lymphocytes activated ex vivo against lacrimal antigens［J］.Cornea，2012，31(6):693-701.
［10］　ZHU Z，ZHU Z，PANG Z，XING Y，LAN D，WANG H.Short hairpin RNA targeting FOXQ1 inhibits invasion and metastasis via the reversal of epithelial-mesenchymal transition in bladder cancer［J］.Int J Oncol，2013，42(4):1271-1278.
［11］　JIA Z，JIAO C，ZHAO S，LI X，REN X，ZHANG L，et al.Immunomodulatory effects of mesenchymal stem cells in a rat corneal allograft rejection model［J］.Exp Eye Res，2012，102:44-49.
［12］　BAKSH D，YAO R，TUAN RS.Comparison of proliferative and multilineage differentiation potential of human mesenchymal stem cells derived from umbilical cord and bone marrow［J］.Stem Cells，2007，27(6):1384-1392.
［13］　CHEN MY，LIE PC，LI ZL，WEI X.Endothelial differentiation of Wharton’s jelly-derived mesenchymal stem cells in comparison with bone marrow-derived mesenchymal stem cells［J］.Exp Hematol，2009，37(5):629-640.
［14］　WEI X，PENG G，ZHENG S，WU X.Differentiation of umbilical cord mesenchymal stem cells into steroidogenic cells in comparison to bone marrow mesenchymal stem cells［J］.Cell Prolif，2012，45(2):101-110.
［15］　GHANNAM S，PNE J，MOQUET-TORCY G，JORGENSEN C，YSSEL H.Mesenchymal stem cells inhibit human Th17 cell differentiation and function and induce a T regulatory cell phenotype［J］.J Immunol，2010，185(1):302-312.
［16］　SVOBODOVA E，KRULOVA M，ZOJICOVA A，POKORNA K，PROCHAZKOWA J，TROSAN P，et al.The role of mouse mesenchymal stem cells in differentiation of naive T-cells into anti-inflammatory regulatory T-cell or proinflammatory helper T-cell 17 population［J］.Stem Cells Dev，2012，21(6):901-910.
［17］　WU CC，WU TC，LIU FL，SYTWU HK，CHANG DM.TNF-α inhibitor reverse the effects of human umbilical cord-derived stem cells onexperimental arthritis by increasing immunosuppression［J］.Cell Immunol，2012，273(1):30-40.
［18］　CHAN JL，TANG KC，PATEL AP，BONILLA LM，PIEROBON N，PONZIO NM，et al.Antigen-presenting property of mesenchymal stem cells occurs during a narrow window at low levels of interferon-gamma［J］.Blood，2006，107(12):4817-4824.
［19］　LIU R，ZHANG Z，LU Z，BORLONGAN C，PAN J，CHEN J，et al.Human umbilical cord stem cells ameliorate experimental autoimmune encephalomyelitis by regulating immunoinflammation and remyelination［J］.Stem Cells Dev，2013，22(7):1053-1062.
［20］　SONG J，CONG S，LI Y,BAI L,CAO G.Human amniotic mesenchymal stem cells inhibit allogeneic lymphocyte proliferation and reduce the secretion of interferon gamma［J］.Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi，2015，31(3):333-337.
［21］　GREGORINI M，BOSIO F，ROCCA C，CORRADETTI V，VALSANIA T，PATTONIERE EF，et al.Mesenchymal stromal cells reset the scatter factor system and cytokine network in experimental kidney transplantation［J］.BMC Immunol，2014，15:44.
［22］　LAROCCA RA，MORAES-VIEIRA PM，BASSI EJ，SEMEDO P，DE ALMEIDA DC,DASILVA MB,et al.Adipose tissue-derived mesenchymal stem cells increase skin allograft survival and inhibit Th-17 immune response［J］.PLoS One，2013，8(10):e76396.
［23］　ZhANGX，REN X，LI G，JIAO C，ZHANG L，ZHAO S，et al.Mesenchymal stem cells ameliorate experimental autoimmune uveoretinitis by comprehensive modulation of systemic autoimmunity［J］.Invest Ophthalmol Vis Sci，2011，52(6):3143-3152.
［24］　KWON MS，NOH MY，OH KW，CHO KA，KANG BY，KIM KS，et al.The immunomodulatory effects of human mesenchymal stem cells on peripheral blood mononuclear cells in ALS patients［J］.J Neurochem，2014，131(2)：206-210.
［25］　XIONG H，YANG XY，HAN J，WANG Q，ZOU ZL.Cytokine expression patterns and mesenchymal stem cell karyotypes from the bone marrow microenvironment of patients with myelodysplastic syndromes［J］.Braz J Med Biol Res，2015，48(3):207-213.

相似文献/References:

[1]贾喆 张晓敏 赵少贞.间充质干细胞对异体角膜移植大鼠CD4+ CD25+ Foxp3+调节性T细胞水平的影响[J].眼科新进展,2012,32(4):000.
[2]秦力维 高原 郭建巍.间充质干细胞治疗眼免疫性疾病的新进展[J].眼科新进展,2013,33(9):000.
[3]李芳,李轩.间充质干细胞在角膜重建中的应用研究进展[J].眼科新进展,2015,35(11):1083.[doi:10.13389/j.cnki.rao.2015.0297]
　LI Fang,LI Xuan.Research progress on applications of MSC in cornea reconstruction[J].Recent Advances in Ophthalmology,2015,35(1):1083.[doi:10.13389/j.cnki.rao.2015.0297]
[4]高凡,王雨生,侯慧媛.两种缺氧模型对小鼠骨髓间充质干细胞中基质金属蛋白酶表达及其对促血管形成能力的影响[J].眼科新进展,2016,36(5):401.[doi:10.13389/j.cnki.rao.2016.0108]
　GAO Fan,WANG Yu-Sheng,HOU Hui-Yuan.Effects of two hypoxia models on expression of matrix metalloproteinase in mesenchymal stem cells and their pro-angiogenesis action[J].Recent Advances in Ophthalmology,2016,36(1):401.[doi:10.13389/j.cnki.rao.2016.0108]
[5]张琛,路晓晓,粘红,等.间充质干细胞治疗干眼的研究进展[J].眼科新进展,2017,37(3):289.[doi:10.13389/j.cnki.rao.2017.0073]
　ZHANG Chen,LU Xiao-Xiao,NIAN Hong,et al.Research progression on mesenchymal stem cells in dry eye[J].Recent Advances in Ophthalmology,2017,37(1):289.[doi:10.13389/j.cnki.rao.2017.0073]
[6]王希莲,路晓晓,杨丽媛,等.间充质干细胞对自身免疫性干眼的免疫调控作用研究进展[J].眼科新进展,2017,37(5):480.[doi:10.13389/j.cnki.rao.2017.0122]
　WANG Xi-Lian,LU Xiao-Xiao,YANG Li-Yuan,et al.Recent advances in immune regulation of mesenchymal stem cells on autoimmune dry eye[J].Recent Advances in Ophthalmology,2017,37(1):480.[doi:10.13389/j.cnki.rao.2017.0122]
[7]韩新红,李艳,李聪伶,等.色素上皮衍生因子基因修饰的脐带间充质干细胞对糖尿病大鼠视网膜组织病理改变的影响[J].眼科新进展,2018,38(2):126.[doi:10.13389/j.cnki.rao.2018.0027]
　HAN Xin-Hong,LI Yan,LI Cong-Ling,et al.Pathological changes in retinal tissue in diabetic rats treated with PEDF gene-modified umbilical cord mesenchymal stem cells[J].Recent Advances in Ophthalmology,2018,38(1):126.[doi:10.13389/j.cnki.rao.2018.0027]
[8]贾喆,李斐,吕瑛,等.间充质干细胞来源外泌体（MSCs-exo）对大鼠角膜移植排斥反应的抑制作用[J].眼科新进展,2018,38(11):1010.[doi:10.13389/j.cnki.rao.2018.0238]
　JIA Zhe,LI Fei,LV Ying,et al.Suppressive effect of exosomes derived from mesenchymal stem cells on keratoplasty rejection[J].Recent Advances in Ophthalmology,2018,38(1):1010.[doi:10.13389/j.cnki.rao.2018.0238]
[9]张梦瑶,汪水风,邵毅.干眼的再生疗法研究进展[J].眼科新进展,2019,39(12):1192.[doi:10.13389/j.cnki.rao.2019.0274]
　ZHANG Meng-Yao,WANG Shui-Feng,SHAO Yi.Regenerative medicine in dry eye[J].Recent Advances in Ophthalmology,2019,39(1):1192.[doi:10.13389/j.cnki.rao.2019.0274]
[10]李东丽,宫媛媛.间充质干细胞源性外泌体对前部缺血性视神经病变患者的治疗潜力[J].眼科新进展,2020,40(5):492.[doi:10.13389/j.cnki.rao.2020.0113]
　LI Dongli,GONG Yuanyuan.Therapeutic potential of mesenchymal stem cells-exosomes for anterior ischemic optic neuropathy[J].Recent Advances in Ophthalmology,2020,40(1):492.[doi:10.13389/j.cnki.rao.2020.0113]
[11]王希莲,路晓晓,杨丽媛,等.间充质干细胞对兔自身免疫性干眼模型病理改变及细胞因子表达的影响[J].眼科新进展,2017,37(8):714.[doi:10.13389/j.cnki.rao.2017.0181]
　WANG Xi-Lian,LU Xiao-Xiao,YANG Li-Yuan,et al.Effects of mesenchymal stem cells on pathological changes and cytokines expression in rabbit model of autoimmune dry eye[J].Recent Advances in Ophthalmology,2017,37(1):714.[doi:10.13389/j.cnki.rao.2017.0181]

备注/Memo

备注/Memo:
国家自然科学基金资助（编号:81100646）；天津市科委自然科学基金资助（编号：11JCYBJC26000、13JCYBJC23300）；教育部留学回国人员科研启动基金资助项目（第48批）；天津市北辰区科技发展计划项目（编号：BC2014-10）
更新日期/Last Update: 2017-02-15