Migration and homing of bone marrow mesenchymal stem cells in segmental nerve injury

doi:10.3969/j.issn.2095-4344.2015.28.008

Abstract

Abstract:

BACKGROUND: A large number of studies have confirmed that tissue-engineered stem cell therapy is feasible to repair peripheral nerve injury, but the repair mechanism is unclear.

OBJECTIVE: To observe the differentiation and homing of bone marrow mesechnymal stem cells under local nerve microenvironment by exploring the migration and effect of bone marrow mesenchymal stem cells in the repair of damaged nerve.

METHODS: Male SD rats, aged 8 weeks, were selected to establish segmental nerve injury models by freezing the sciatic nerve. Thirty-six model rats were randomized into three groups (n=12): frozen nerve injury group, cell injection into the nerve group, cell injection around the nerve group. Before modeling and at 4, 8, 12 weeks after cell implantation, the sciatic nerve function index was measured. Electrophysiological test, contractility recovery rate, wet weight recovery rate of the triceps surae were detected and Masson staining was performed; toluidine blue staining of the distal nerve injury and immunofluorescence staining of the damaged nerve were performed.

RESULTS AND CONCLUSION: At 4, 8, 12 weeks after cell implantation, the sciatic nerve function index was ranked as follows: frozen nerve injury group < cell injection around the nerve group < cell injection into the nerve group, but no significant difference was found among the three groups. Electrophysiological results showed that there was no difference in the latency and amplitude of compound muscle action potential between two cell therapy groups, but compared with the frozen nerve injury group, the latency was shorter and the amplitude was higher in the two cell therapy groups (P < 0.05). Cross-sectional area of the muscle fibers was lower in the frozen nerve injury group compared with the other two groups. Immunofluorescence staining showed that Nestin, S100 and P0 proteins were all expressed in the two cell therapy groups 12 weeks after cell implantation. These findings indicate that bone marrow mesenchymal stem cells added into the surrounding tissues of segmental damaged nerve can migrate into the damaged nerve, and even differentiate into Schwann cells and neural stem cells, which has a similar effect to the cell injection into the damaged cells.

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

Key words: Sciatic Nerve, Trauma, Nervous System, Bone Marrow, Mesenchymal Stem Cell Transplantation

CLC Number:

R394.2

Zhou Xue-feng, Ren Zhi-wu, Lu Ming, Wang Yu, Sun Zhen, Peng Jiang. Migration and homing of bone marrow mesenchymal stem cells in segmental nerve injury[J]. Chinese Journal of Tissue Engineering Research, 2015, 19(28): 4465-4471.

Figures/Tables 4

References

[1] Siemionow M, Brzezicki G. Chapter 8: Current techniques and concepts in peripheral nerve repair. Int Rev Neurobiol. 2009; 87:141-172.

[2] Millesi H. Techniques for nerve grafting. Hand Clin. 2000; 16(1): 73-91.

[3] Dornseifer U, Matiasek K, Fichter MA, et al. Surgical therapy of peripheral nerve lesions: current status and new perspectives. Zentralbl Neurochir. 2007;68(3):101-110.

[4] Roganovic Z, Ilic S, Savic M. Radial nerve repair using an autologous denatured muscle graft: comparison with outcomes of nerve graft repair. Acta Neurochir (Wien). 2007; 149(10):1033-1038.

[5] Xue C, Hu N, Gu Y, et al. Joint use of a chitosan/PLGA scaffold and MSCs to bridge an extra large gap in dog sciatic nerve. Neurorehabil Neural Repair. 2012;26(1):96-106.

[6] Frerichs O, Fansa H, Schicht C,et al. Reconstruction of peripheral nerves using acellular nerve grafts with implanted cultured Schwann cells. Microsurgery. 2002;22(7):311-315.

[7] .Lin H, Liu F, Zhang C, et al. Pluripotent hair follicle neural crest stem-cell-derived neurons and schwann cells functionally repair sciatic nerves in rats. Mol Neurobiol. 2009; 40(3):216-223.

[8] Zhang CS, Lv G.Repair of sciatic nerve defects using tissue engineered nerves.Neural Regen Res. 2013;8(21): 1985- 1994.

[9] Wang Y, Zhao Z, Ren Z, et al. Recellularized nerve allografts with differentiated mesenchymal stem cells promote peripheral nerve regeneration. Neurosci Lett. 2012;514(1): 96-101.

[10] Wang D, Liu XL, Zhu JK, et al. Repairing large radial nerve defects by acellular nerve allografts seeded with autologous bone marrow stromal cells in a monkey model. J Neurotrauma. 2010;27(10):1935-1943.

[11] Smit X, van Neck JW, Ebeli MJ, et al. Static footprint analysis: a time-saving functional evaluation of nerve repair in rats. Scand J Plast Reconstr Surg Hand Surg. 2004;38(6):321- 325.

[12] 赵喆. 以天然神经细胞外基质为支架构建组织工程神经修复周围神经缺损[D].北京:军医进修学院,2011.

[13] Zhao Z, Wang Y, Peng J, et al. Repair of nerve defect with acellular nerve graft supplemented by bone marrow stromal cells in mice. Microsurgery. 2011;31(5):388-394.

[14] 沈宁江,朱家恺.小腿三头肌肌力评价坐骨神经运动功能恢复的实验研究[J].中华显微外科杂志,1994,17(4):266-268.

[15] 赵曙光,李辉,范慧敏. 低温冷冻神经损伤与再生研究[J]. 同济大学学报:医学版,2010,31(4):15-18.

[16] Fasano VA, Peirone SM, Zeme S, et al. Cryoanalgesia. Ultrastructural study on cryolytic lesion of sciatic nerve in rat and rabbit. Acta Neurochir Suppl (Wien). 1987;39:177-180.

[17] 孙江森,李彪,龚跃昆. 骨髓间充质干细胞标记及示踪技术的研究与进展[J]. 中国组织工程研究,2012,16(6):1107-1110.

[18] Chopp M, Li Y. Treatment of neural injury with marrow stromal cells. Lancet Neurol. 2002;1(2):92-100.

[19] Zhang YR,Zhang H,Zhang GC,et al.Combining acellular nerve allografts with brain-derived neurotrophic factor transfected bone marrow mesenchymal stem cells restores sciatic nerve injury better than either intervention alone. Neural Regen Res. 2014;9(20): 1814-1819.

[20] Totey S, Totey S, Pal R, et al. Adult stem cells: a clinical update. J Stem Cells. 2009;4(2):105-121.

[21] Wang J, Ding F, Gu Y, et al. Bone marrow mesenchymal stem cells promote cell proliferation and neurotrophic function of Schwann cells in vitro and in vivo. Brain Res. 2009;1262:7-15.

[22] Guérette D, Khan PA, Savard PE, et al. Molecular evolution of type VI intermediate filament proteins. BMC Evol Biol. 2007;7: 164.

[23] Cocchia D, Miani N. Immunocytochemical localization of the brain-specific S-100 protein in the pituitary gland of adult rat. J Neurocytol. 1980;9(6):771-782.

[24] Ghandour MS, Langley OK, Labourdette G, et al. Specific and artefactual cellular localizations of S 100 protein: an astrocyte marker in rat cerebellum. Dev Neurosci. 1981;4(1):66-78.

[25] 张殿英,姜保国,傅忠国,等. 周围神经损伤后S-100蛋白的分布和变化研究[J].中国矫形外科杂志,2002,9(4):348-350.

[26] Kim S, Jeon TJ, Oberai A, et al. Transmembrane glycine zippers: physiological and pathological roles in membrane proteins. Proc Natl Acad Sci U S A. 2005;102(40):14278- 14283.

[27] Kochański A. Mutations in the Myelin Protein Zero result in a spectrum of Charcot-Marie-Tooth phenotypes. Acta Myol. 2004;23(1):6-9.