Mechanisms of the Immunomodulation Effects of Bone Marrow-Derived Mesenchymal Stem Cells on Facial Nerve Injury in Sprague-Dawley Rats

被引:13
作者
Ge, Yining [1 ,2 ,3 ,4 ]
Zhang, Yongli [1 ,2 ,3 ]
Tang, Qi [1 ,2 ,3 ]
Gao, Juanjuan [1 ,2 ,3 ]
Yang, Hua [1 ,2 ,3 ]
Gao, Zhiqiang [1 ,2 ,3 ]
Zhao, Robert Chunhua [2 ,5 ,6 ]
机构
[1] Chinese Acad Med Sci, Peking Union Med Coll Hosp, Dept Otolaryngol, 1 Shuaifuyuan Wangfujing Dongcheng Dist, Beijing 100730, Peoples R China
[2] Peking Union Med Coll, 1 Shuaifuyuan Wangfujing Dongcheng Dist, Beijing 100730, Peoples R China
[3] Chinese Acad Med Sci, Peking Union Med Coll Hosp, Translat Med Ctr, Dept Otolaryngol, Beijing, Peoples R China
[4] Shanghai Jiao Tong Univ, Sch Med, Renji Hosp, Dept Head & Neck Surg, Shanghai, Peoples R China
[5] Chinese Acad Med Sci, Ctr Excellence Tissue Engn, Inst Basic Med Sci, Dept Cell Biol,Key Lab Beijing, Beijing, Peoples R China
[6] Chinese Acad Med Sci, Sch Basic Med, Beijing, Peoples R China
基金
中国国家自然科学基金; 北京市自然科学基金;
关键词
immunomodulation; mesenchymal stem cells; facial nerve; motor neurons; DORSAL-ROOT GANGLIA; GROWTH-FACTOR-BETA; STROMAL CELLS; MOTONEURON SURVIVAL; T-LYMPHOCYTE; DIFFERENTIATION; TRAFFICKING; SUPPRESSION; EXPRESSION; RESPONSES;
D O I
10.1089/scd.2018.0104
中图分类号
Q813 [细胞工程];
学科分类号
摘要
Normal facial nerve (FN) function is very important for human being. However, if injured, FN function is difficult to restore completely. Recently, many studies reported the immune regulation function of stem cells (SCs). However, the immunomodulation function of SCs on FN injury is still unclear. Our study aims to explore the mechanism of immunomodulation effect of Sprague-Dawley rat bone marrow-derived SCs (BMSCs) on FN injury and specially focus on the regulation of Th17 and the protection effects of BMSCs on central facial motor neurons (FMNs). First, rat FNs were harvested. FN and BMSCs were cultured together or separately and levels of transforming growth factor (TGF)-beta 1, interleukin (IL)-6, hepatocyte growth factor (HGF), inducible nitric oxide synthase (iNOS), and prostaglandin E2 (PGE2) in supernatant were detected by enzyme-linked immunosorbent assay (ELISA). Then, after treating with or without local BMSCs injection, the proportion of Th17 in neck lymph nodes (LNs) was investigated in rat FN injury models. Furthermore, the apoptotic index of FMNs was studied in rat FN injury models that were treated with or without BMSCs. We found that BMSCs could secrete high levels of IL-6, HGF, PGE2, iNOS, and TGF-beta 1 in culture. The percentage of Th17 of neck LNs in BMSCs-treated group was significantly lower than that in the control group. The apoptotic index of FMNs in BMSCs-treated group was significantly lower than that in the control group. In conclusion, our research indicates BMSCs could independently secrete cytokines IL-6, HGF, PGE2, iNOS, and TGF-beta 1, and these cytokines could regulate the balance among subsets of CD4(+) T cells and could protect FMNs by inhibiting neuron apoptosis.
引用
收藏
页码:489 / 496
页数:8
相关论文
共 35 条
[21]  
2-3
[22]   Brain-derived neurotrophic factor supports facial motoneuron survival after facial nerve transection in immunodeficient mice [J].
Serpe, CJ ;
Byram, SC ;
Sanders, VM ;
Jones, KJ .
BRAIN BEHAVIOR AND IMMUNITY, 2005, 19 (02) :173-180
[23]   CD4+ T, but not CD8+ or B, lymphocytes mediate facial motoneuron survival after facial nerve transection [J].
Serpe, CJ ;
Coers, S ;
Sanders, VM ;
Jones, KJ .
BRAIN BEHAVIOR AND IMMUNITY, 2003, 17 (05) :393-402
[24]   Functional recovery after facial nerve crush is delayed in severe combined immunodeficient mice [J].
Serpe, CJ ;
Tetzlaff, JE ;
Coers, S ;
Sanders, VM ;
Jones, KJ .
BRAIN BEHAVIOR AND IMMUNITY, 2002, 16 (06) :808-812
[25]  
Serpe CJ, 1999, J NEUROSCI, V19
[26]   Mechanisms of immune suppression by interleukin-10 and transforming growth factor-β:: the role of T regulatory cells [J].
Taylor, A ;
Verhagen, J ;
Blaser, K ;
Akdis, M ;
Akdis, CA .
IMMUNOLOGY, 2006, 117 (04) :433-442
[27]   Suppression of allogeneic T-cell proliferation by human marrow stromal cells: Implications in transplantation [J].
Tse, WT ;
Pendleton, JD ;
Beyer, WM ;
Egalka, MC ;
Guinan, EC .
TRANSPLANTATION, 2003, 75 (03) :389-397
[28]   Effects of facial nerve axotomy on Th2-and Th1-associated chemokine expression in the facial motor nucleus of wild-type and presymptomatic mSOD1 mice [J].
Wainwright, Derek A. ;
Xin, Junping ;
Mesnard, Nichole A. ;
Politis, Christine M. ;
Sanders, Virginia M. ;
Jones, Kathryn J. .
JOURNAL OF NEUROIMMUNOLOGY, 2009, 216 (1-2) :66-75
[29]   USE OF STEM CELLS TO AUGMENT NERVE INJURY REPAIR [J].
Walsh, Sarah ;
Midha, Rajiv .
NEUROSURGERY, 2009, 65 (04) :A80-A86
[30]  
Wang Lei, 2002, Hematology, V7, P113