Transplantation of bone marrow mesenchymal stem cells for denervated muscular atrophy

doi:10.3969/j.issn.2095-4344.2094

Abstract

Abstract:

BACKGROUND: Microscopic surgery or some adjuvant treatments can neither effectively delay nor treat denervated muscle atrophy by repairing damaged nerve cells. Studies have found that bone marrow mesenchymal stem cells have the potential for directional differentiation and repair damaged tissues under certain environmental factors. It is speculated that the cells can play a certain role in repairing denervated atrophic muscles.

OBJECTIVE: To investigate whether transplantation of bone marrow mesenchymal stem cells can alleviate and retard atrophy of denervated muscles.

METHODS: Primary bone marrow mesenchymal stem cells were isolated from Sprague-Dawley rats, and passage 3 cells were labeled by BrdU for cell transplantation. Thirty Sprague-Dawley rats were divided into three groups, 10 rats in each group. In the sham operation group, only the main trunk of the sciatic nerve was exposed but not clamped. In the treatment group, the main trunk of the sciatic nerve was clamped and bone marrow mesenchymal stem cell suspension was injected into the gastrocnemius muscle. In the control group, after the sciatic nerve trunk was clamped, the gastrocnemius muscle innervated by the sciatic nerve was injected with DMEM medium of equal volume (without cells and fetal bovine serum). Basso, Beattie and Bresnahan scores were used to evaluate the motor function of the rat’s left hindlimb at 1 and 2 weeks after cell transplantation. Changes in the gastrocnemius muscle fibers were observed by hematoxylin-eosin staining and BrdU immunohistochemical staining at 14 days after cell transplantation.

RESULTS AND CONCLUSION: The passage 3 bone marrow mesenchymal stem cells were positive for BrdU. The labeled cells could survive in and repair the denervated muscle tissue in the treatment group. Compared with the model group, the denervated muscle fibers of the treatment group recovered from mutual fusion and re-arranged regularly. To conclude, transplantation of bone marrow mesenchymal stem cells can alleviate and retard atrophy of denervated muscles.

Key words:

peripheral nerve injury, denervated muscle atrophy, bone marrow mesenchymal stem cells, cell transplantation, BrdU, gastrocnemius muscle

CLC Number:

Yang Ying, Yan Nan, Tian Wei, Han Cao, Zhang Xiaoyan, Zheng Xin, Liu Shidan, Zhang Shuo, Wang Zhengdong. Transplantation of bone marrow mesenchymal stem cells for denervated muscular atrophy [J]. Chinese Journal of Tissue Engineering Research, 2020, 24(25): 4000-4005.

Figures/Tables 5

References

[1] SAMII A, CARVALHO GA, SAMII M. Brachial plexus injury: factors affecting functional outcome in spinal accessory nerve transfer for the restoration of elbow flexion. J Neurosurg. 2003;98(2):307-312.

[2] 顾立强,裴国献.周围神经损伤基础与临床[J].北京:人民军医出版社,2001: 70,157.

[3] DASARI VR, VEERAVALLI KK, TSUNG AJ, et al. Neuronal apoptosis is inhibited by cord blood stem cells after spinal cord injury. J Neurotrauma. 2009;26(11):2057-2069.

[4] 吴佳佳,徐建光,马书杰.失神经骨骼肌萎缩的机制及康复治疗[J].安徽医药, 2017,21(11):1949-1953.

[5] 贺菊芳,余资江,戈果,等.大鼠坐骨神经损伤手术时机选择的实验研究[J].贵州医科大学学报,2016,41(10):1122-1127.

[6] 董英,徐昂,姜影,等.运动训练结合针刺对坐骨神经损伤大鼠肌力和神经纤维恢复的影响[J].滨州医学院学报, 2016,39(5):327-329.

[7] 马书杰,严隽陶,黄品贤,等.推拿手法防治失神经骨骼肌萎缩的实验研究[J].江苏中医药,2014,46 (11):79-81.

[8] 刘磊.电刺激对失神经骨骼肌萎缩中核因子-КB、肌肉环状指蛋白-1表达变化的影响[J].北方药学,2013,10 (8):81.

[9] 裴艳宏,刘坤祥.黄芪丹参联合对大鼠失神经骨骼肌萎缩的作用[J].中国医学工程,2013,21 (9):5-6.

[10] 付秀美,王荣良,杨海艳,等.脂肪源性干细胞对大鼠坐骨神经功能恢复的影响[J].承德医学院学报,2016,33(6):451-453.

[11] 贺菊芳,余资江.神经干细胞移植治疗周围神经损伤的研究进展[J].贵州医科大学学报,2016,41(10):1117-1121.

[12] 蔡学华,吕艳丽.坐骨神经损伤修复机制及治疗效果评价[J].双足与保健, 2017,26(23):112,114.

[13] 方洪松,周建林,彭昊,等.不同来源间充质干细胞生物学特性差异[J].中国组织工程研究,2015,19(32):5243-5248.

[14] 蒲超,张珊珊,李伟,等.犬骨髓间充质干细胞体外分离培养及分化鉴定[J].川北医学院学报,2016,31(6):782-785.

[15] 杨俊丽,韩霞,孙明启,等.兔骨髓间充质干细胞的生物学特征及原代培养[J].中国组织工程研究,2015,19(50):8043-8047.

[16] 李丹,张金国.大鼠骨髓间充质干细胞体外培养体系的建立[J].济宁医学院学报,2015,38(5):321-323.

[17] 宋珂,石琦,青莹,等.大鼠骨髓间充质干细胞分离培养及鉴定的相关研究[J].临床口腔医学杂志,2015,31(9):531-536.

[18] 易敏,付必莽,李志伟,等.兔骨髓间充质干细胞的培养及初步鉴定[J].昆明医科大学学报,2015,36(9):17-19.

[19] 阮光萍,刘菊芬,王金祥,等.鸡卵清提取液促进C57小鼠骨髓间充质干细胞增殖的研究[J].西南国防医药,2015,25(8):826-828.

[20] DOCHEVA D, POPOV C, MUTSCHLER W, et al. Human mesenchymal stem cells in contact with their environment: surface characteristics and the integrin system. J Cell Mol Med. 2007;11(1):21-38.

[21] ZAPPIA E, CASAZZA S, PEDEMONTE E, et al. Mesenchymal stem cells ameliorate experimental autoimmune encephalomyelitis inducing T-cell anergy. Blood. 2005;106(5):1755-1761.

[22] LI Y, CHEN J, CHEN XG, et al. Human marrow stromal cell therapy for stroke in rat: neurotrophins and functional recovery. Neurology. 2002; 59(4):514-523.

[23] SASAKI M, RADTKE C, TAN AM, et al. BDNF-hypersecreting human mesenchymal stem cells promote functional recovery, axonal sprouting, and protection of corticospinal neurons after spinal cord injury. J Neurosci. 2009;29(47):14932-14941.

[24] CARONI P. Activity-sensitive signaling by muscle-derived insulin-like growth factors in the developing and regenerating neuromuscular system. Ann N Y Acad Sci. 1993;692:209-222.

[25] 王佃亮,李燕妮.间充质干细胞移植治疗作用机制[J].转化医学杂志, 2019, 8(5):257-261.

[26] 黄华, Raynald,安沂华,等. 移植人骨髓间充质干细胞促进大鼠脊髓损伤后的神经功能恢复[J].武警后勤学院学报(医学版), 2016,25(11):865-868.

[27] 冯烨军,陈明.骨髓间充质干细胞在神经修复中的研究进展[J].神经损伤与功能重建,2016,11(5):426-428.

[28] 刘晓光,肖卫华,赵淋淋,等.间充质干细胞移植治疗骨骼肌损伤的研究进展[J].中国康复医学杂志,2015,30(12):1313-1317.

[29] 肖恒军,转黎,陈俊,等.大鼠骨髓间充质干细胞体外定向诱导分化成平滑肌细胞[J].中国男科学杂志,2015,29(9):3-6.

[30] 黄蓉,梁瑜祯,卢炳丰,等.自体骨髓间充质干细胞移植促进缺血下肢血管新生的实验研究[J].医学研究生学报, 2015,28(7):706-710.

[31] 刘青峰,王葳,王亿龙.骨髓间充质干细胞移植对放射性肠损伤大鼠的修复作用及对JAK/STAT通路的影响[J].中国药物与临床, 2018,18(2):163-166.

[32] 王灵战,王立群,孟壮志,等.大鼠比目鱼肌肌纤维总数、横截面积及其内慢肌纤维和快肌纤维横截面积与年龄相关的变化[J].解剖学报,2015,46(5): 660-666.

[33] 罗涛,王彤敏,李力燕.EdU与BrdU在检测细胞增殖中的特点及应用进展[J].重庆医学,2015,44(32):4581-4583.

[34] 高黎,祝华,张荣,等.BrdU标记人脐带间充质干细胞及对细胞生物学行为影响的体外研究[J].重庆医科大学学报, 2014, 39(11):1617-1621.

[35] 许伟,谢兴文,赵永利,等.Brdu标记的rBMSCs在大鼠体内的迁移[J].中国骨质疏松杂志,2015,21(4):409-414.

[36] ZAIM M, KARAMAN S, CETIN G, et al. Donor age and long-term culture affect differentiation and proliferation of human bone marrow mesenchymal stem cells. Ann Hematol. 2012;91(8):1175-1186.

[37] 张明鸣,贾贵清,程惊秋,等.大鼠骨髓间质干细胞的BrdU体外标记和体内示踪研究[J].四川大学学报(医学报), 2012,43(2):266-270.

[38] MEYER JS, KOEHM SL, HUGHES JM, et al. Bromodeoxyuridine labeling for S-phase measurement in breast carcinoma. Cancer. 1993; 71(11):3531-3540.

[39] CUEVAS P, CARCELLER F, DUJOVNY M, et al. Peripheral nerve regeneration by bone marrow stromal cells. Neurol Res. 2002;24(7): 634-638.

[40] 陈菁,楚燕飞,顾玉东,等.培养雪旺细胞 NGF、CNTF 和 GDNF 共表达和共定位实验研究[J].中华手外科杂志, 2005,21(5):317-319.

[41] 邱超,郑亚妮,许硕贵.骨髓间充质干细胞移植对周围神经损伤后施旺细胞的影响[J].组织工程与重建外科杂志, 2018,14(1):28-30.

[42] 田春艳,潘月彩.神经生长因子治疗周围神经损伤的临床价值分析[J].中国医药指南,2016,14(36):152-153.

[43] 蔡明轩,颜南,王正东,等.神经细胞分泌因子促进骨骼肌细胞生长[J].中国组织工程研究,2016,20(42):6324-6329.

[44] NAKAMURA Y, MIYAKI S, ISHITOBI H, et al. Mesenchymal-stem-cell- derived exosomes accelerate skeletal muscle regeneration. FEBS Lett. 2015;589(11):1257-1265.

[45] 李鹏,郭修田.骨髓间充质干细胞成肌分化在骨骼肌再生中的应用[J].中华细胞与干细胞杂志,2018,8(3):187-191.

[46] 侯晓乐,李爱国,杨林,等.骨髓间充质干细胞移植对失神经肌肉萎缩大鼠的影响[J].新乡医学院学报,2015,32(5):391-394.

[47] KIM SS, YOO SW, PARK TS, et al. Neural induction with neurogenin1 increases the therapeutic effects of mesenchymal stem cells in the ischemic brain. Stem Cells. 2008;26(9):2217-2228.