Effects of umbilical cord Wharton’s jelly mesenchymal stem cell transplantation on the expression of inflammatory factors in rats with spinal cord injury

doi:10.3969/j.issn.2095-4344.2015.23.021

Abstract

Abstract:

BACKGROUND: The production and release of a large amount of inflammatory factors caused by immune system inflammatory response mainly contributes to secondary spinal cord injury.
OBJECTIVE: To investigate the effects of umbilical cord Wharton’s jelly mesenchymal stem cell transplantation on repair of injured neurological function and expression of inflammatory factors monocyte chemoattractant protein 1 and interleukin 10 in rats with acute spinal cord injury.
METHODS: Eighty-one healthy adult male Sprague-Dawley rats were randomly and equally divided into sham operation, model and cell transplantation groups, with 27 rats per group. Rats in the latter two groups were subjected to hemisection of the spinal cord to establish acute spinal cord injury models. Rat models in the cell
transplantation group received umbilical cord Wharton’s jelly mesenchymal stem cell injection (1×10⁶) via the tail vein. Rat neurological function was evaluated using the BBB score at different time points after spinal cord injury. The expression of monocyte chemoattractant protein 1 and interleukin 10 in injured spinal cord tissue was detected using ELISA assay at different time points after spinal cord injury. Migration and neuronal differentiation of umbilical cord Wharton’s jelly mesenchymal stem cells in the injured spinal cord tissue were determined using immunohistochemical staining method.
RESULTS AND CONCLUSION: Compared with the sham operation and model groups, rat neurological function was significantly recovered in the cell transplantation group (P < 0.05). Compared to the model group, monocyte chemoattractant protein 1 level in the serum and monocyte chemoattractant protein 1 mRNA and protein expression in the injured spinal cord tissue were significantly lower (P < 0.05), but interleukin 10 mRNA and protein expression in the injured spinal cord tissue was significantly higher (P < 0.05), in the cell transplantation group. In the cell transplantation group, umbilical cord Wharton’s jelly mesenchymal stem cells could migrate to the injured region and express glial fibrillary acidic protein. These findings suggest that umbilical cord Wharton’s jelly mesenchymal stem cells promote rat neurological function recovery by regulating the inflammatory response in the injured spinal cord tissue, which is likely to be one of mechanisms by which transplantation of umbilical cord Wharton’s jelly mesenchymal stem cells treats spinal cord injury.

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

CLC Number:

R394.2

Ma Shan-shan, Qu Rui-na, Tian Yi, Yao Ning, Cui Yuan-bo, Han Kang, Xing Qu, Yang Bo, Guan Fang-xia. Effects of umbilical cord Wharton’s jelly mesenchymal stem cell transplantation on the expression of inflammatory factors in rats with spinal cord injury [J]. Chinese Journal of Tissue Engineering Research, 2015, 19(23): 3729-3735.

Figures/Tables 5

References

[1] Torres-Espín A, Redondo-Castro E, Hernández J, et al. Bone marrow mesenchymal stromal cells and olfactory ensheathing cells transplantation after spinal cord injury--a morphological and functional comparison in rats. Eur J Neurosci. 2014; 39(10):1704-1717.

[2] Oliveri RS, Bello S, Biering-Sørensen F. Mesenchymal stem cells improve locomotor recovery in traumatic spinal cord injury: systematic review with meta-analyses of rat models. Neurobiol Dis. 2014;62:338-353.

[3] Wang L, Wang Q, Zhang XM. Progress on bone marrow mesenchymal stem cells transplantation for spinal cord injury. Zhongguo Gu Shang. 2014;27(5):437-440.

[4] Yao LQ, He C, Zhao Y,et al.Human umbilical cord blood stem cell transplantation for the treatment of chronic spinal cord injury.Neural Regen Res. 2013;8(5): 397-403

[5] Zhang C, He XJ, Li HP,et al.Chondroitinase ABC plus bone marrow mesenchymal stem cells for repair of spinal cord injury.Neural Regen Res. 2013;8(11): 965-974

[6] Tanna T, Sachan V. Mesenchymal stem cells: potential in treatment of neurodegenerative diseases. Curr Stem Cell Res Ther. 2014;9(6):513-521.

[7] Dasari VR, Veeravalli KK, Dinh DH. Mesenchymal stem cells in the treatment of spinal cord injuries: A review. World J Stem Cells. 2014;6(2):120-133.

[8] 魏开斌,卓锋,刘红,等. 移植脐带间充质干细胞治疗脊髓损伤的实验研究[J].中国矫形外科杂志,2012,20(22):2081-2085.

[9] 刘静,韩冬梅,王志东,等.脐带间充质干细胞治疗脊髓损伤临床分析[J].中华损伤与修复杂志:电子版,2011,6(4):564-570, 576.

[10] 王颖,冯世庆,赵鹏,等.大鼠脊髓损伤后不同时期移植人脐带间充质干细胞的修复效果观察[J].中国脊柱脊髓杂志,2010,20(11): 918-925.

[11] 韩明远,冯世庆,李辉,等. 移植人脐带间充质干细胞修复大鼠脊髓损伤[J].中国组织工程研究与临床康复,2010,14(19):3483- 3489.

[12] 朱玉海,冯世庆,孔晓红,等. 人脐带间充质干细胞与自体激活雪旺细胞联合移植修复脊髓损伤的实验研究[J].中华创伤骨科杂志,2009,11(8):747-751.

[13] Ormond DR, Shannon C, Oppenheim J, et al. Stem cell therapy and curcumin synergistically enhance recovery from spinal cord injury. PLoS One. 2014;9(2):e88916.

[14] 锁志刚,丁惠强,飞翔,等. Caspase-1及其下游炎症因子在大鼠脊髓损伤中的表达及意义[J].宁夏医科大学学报, 2011, 33(1):48-51.

[15] Nelissen S, Vangansewinkel T, Geurts N, et al. Mast cells protect from post-traumatic spinal cord damage in mice by degrading inflammation-associated cytokines via mouse mast cell protease 4. Neurobiol Dis. 2014;62:260-272.

[16] 徐玉生,李星辰,金伟林,等.褪黑素对大鼠急性脊髓损伤后不同时期IL-10表达的影响[J].郑州大学学报:医学版, 2013, 48(2): 193-197.

[17] 渠瑞娜,马珊珊,田毅,等.人脐带沃顿胶干细胞对急性大鼠脊髓损伤的作用及脊髓组织中 TNF-α和 BDNF 表达的影响[J]. 郑州大学学报:医学版, 2014, 49(6):765-769.

[18] 张文进,黄华,关方霞,等.人脐带间充质干细胞治疗脊髓损伤及其对内源性细胞增殖的影响[J]. 实用医学杂志, 2013, 29(6): 880-882.

[19] 董锋,林建华,吴朝阳.骨髓间质干细胞经静脉移植对大鼠脊髓损伤后TNF-α、IL-1β mRNA表达的影响[J]. 中国骨与关节损伤杂志, 2010, 25(8):697-699.

[20] Tsumuraya T, Ohtaki H, Song D, et al. Human mesenchymal stem/stromal cells suppress spinal inflammation in mice with contribution of pituitary adenylate cyclase-activating polypeptide (PACAP). J Neuroinflammation. 2015;12:35.

[21] Urdzíková LM, R??i?ka J, LaBagnara M, et al. Human mesenchymal stem cells modulate inflammatory cytokines after spinal cord injury in rat. Int J Mol Sci. 2014;15(7): 11275- 11293.

[22] Basso DM, Beattie MS, Bresnahan JC. A sensitive and reliable locomotor rating scale for open field testing in rats. J Neurotrauma. 1995;12(1):1-21.

[23] Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 2001;25(4):402-408.

[24] Cheng T, Yang B, Li D, et al. Wharton's Jelly Transplantation Improves Neurologic Function in a Rat Model of Traumatic Brain Injury. Cell Mol Neurobiol. 2015 Feb 1. [Epub ahead of print]

[25] 王革生, 张庆俊, 韩忠朝. 人脐带间充质干细胞移植对大鼠脊髓损伤神经功能恢复的评价[J].中华神经外科杂志,2006, 22(1): 18-21.

[26] 朱青,汪晶,刘元渊,等.脊髓损伤的病理机制和细胞移植治疗进展[J].神经损伤与功能重建, 2013, 8(3): 217-220.

[27] 谢周通,徐皓,陈建梅,等.免疫因素在脊髓损伤中的作用[J].中国组织工程研究, 2013, 17(37): 6664-6670.

[28] 郑晶晶,姚安会,刘芳芳,等.小鼠脊髓损伤早期不同炎症因子的表达变化[J]. 细胞与分子免疫学杂志, 2012, 28(4):391-394.

[29] 王晓凯,孙天胜,李放,等. SIRT1对大鼠急性脊髓损伤炎症反应的影响[J]. 中华临床医师杂志, 2012, 6(12):3250-3253.

[30] 张群,王竞秋,宋焱峰,等.大鼠急性脊髓损伤后MCP-1及BDNF表达变化的实验研究[J].甘肃医药, 2013, 32(3): 184-186.

[31] Yang CC, Shih YH, Ko MH, et al. Transplantation of human umbilical mesenchymal stem cells from Wharton's jelly after complete transection of the rat spinal cord. PLoS One. 2008; 3(10):e3336.

[32] Zhang L, Zhang HT, Hong SQ, et al. Cografted Wharton's jelly cells-derived neurospheres and BDNF promote functional recovery after rat spinal cord transection. Neurochem Res. 2009;34(11):2030-2039.

[33] 赵峰,李圣青,遆新宇,等.骨髓间充质干细胞对肺损伤大鼠转化生长因子β及单核细胞趋化蛋白1的影响[J].中国组织工程研究与临床康复, 2008,12(29): 5627-5630.

[34] 罗文芳. 脑出血大鼠神经干细胞移植后IL-2、IL-10的表达及中药干预的影响[D]. 长沙:中南大学, 2008.

[35] Wakabayashi K, Nagai A, Sheikh AM, et al. Transplantation of human mesenchymal stem cells promotes functional improvement and increased expression of neurotrophic factors in a rat focal cerebral ischemia model. J Neurosci Res. 2010;88(5):1017-1025.

[36] Wei CC, Lin AB, Hung SC. Mesenchymal stem cells in regenerative medicine for musculoskeletal diseases: bench, bedside, and industry. Cell Transplant. 2014;23(4-5):505-512.

[37] Tan Y, Uchida K, Nakajima H, et al. Blockade of interleukin 6 signaling improves the survival rate of transplanted bone marrow stromal cells and increases locomotor function in mice with spinal cord injury. J Neuropathol Exp Neurol. 2013; 72(10):980-993.

[38] 孔令胜,靳峰,郭强,等.胎鼠神经干细胞移植对大鼠脊髓损伤后神经元特异性烯醇化酶和皮质体感诱发电位的影响研究[J].中国全科医学,2013,16(6):639-643.

[39] Dai G, Liu X, Zhang Z, et al. Transplantation of autologous bone marrow mesenchymal stem cells in the treatment of complete and chronic cervical spinal cord injury. Brain Res. 2013;1533:73-79.

[40] 董锋,林建华,吴朝阳. 骨髓间充质干细胞静脉移植脊髓损伤大鼠肿瘤坏死因子α及白细胞介素1β的表达[J].中国组织工程研究, 2012, 16(36):6730-6735.

[41] 张健,李勇,王文军,等. HUCMSCs移植对大鼠亚急性脊髓损伤GAP-43和SPRR1A蛋白表达及神经功能的影响[J].医学临床研究,2013,30(6):1070-1073.

[42] 白金柱,王岩,刘忠军,等.经静脉移植间充质干细胞在脊髓损伤鼠体内的迁移[J].中国临床康复,2006,10(25):30-33.

[43] 周志刚,李志忠,林永新,等.人脐带间充质干细胞定向诱导分化成类神经元的实验研究[J].中国病理生理杂志,2015,31(2):229- 233.