REGULATORY EFFECT OF OLFACTORY ENSHEATHING CELLS ON INFLAMMATORY CYTOKINES IN REPAIR OF RAT SCIATIC NERVE DEFECT_Chinese Journal of Reparative and Reconstructive Surgery

Authors：

YAODongdong ^1,2 , ZHANGJieyuan ³ , LIBingcang ³ , ZHOUChan ⁴ ,  LIUBin ^1,2

1. School of Life Sciences, Southwest University, Chongqing, 400715, P. R. China;
2. Key Laboratory of Freshwater Fish Reproduction and Development, Ministry of Education, Chongqing, 400715, P. R. China;
3. Research Institute of Surgery, Daping Hospital/State Key Laboratory of Trauma, Burns, and Combined Injury, Third Military Medical University, Chongqing, 400715, P. R. China;
4. Chongqing Academy of Animal Science, Chongqing, 400715, P. R. China;

Corresponding author：

LIUBin, Email: xytom@swu.edu.cn

Keywords：

Peripheral nerve regeneration; Olfactory ensheathing cell; Anti-inflammation cytokine; Pro-inflammatory cytokine; Rat

DOI：

10.7507/1002-1892.20160317

Video：

Export PDF Favorites Scan Get Citation

Abstract Full text Figures/Tables Video References Cited by

Objective To investigate the expression regulation of inflammation cytokines interleukin 4 (IL-4), IL-6, IL-13, and tumor necrosis factor α (TNF-α) in rats with sciatic nerve defect following olfactory ensheathing cell (OEC) transplantation. Methods The primary OEC for cell culture and identification was dissociated from the olfactory bulb of the green fluorescent protein-Sprague Dawley (GFP-SD) rat. One hundred SD rats were randomly divided into 2 groups, and the right sciatic nerve defect (10 mm in length) model was made, then repaired with poly (lactic acid-co-glycolic acid) (PLGA). The mixture of equivalent cultured GFP-OEC and extracellular matrix (ECM) was injected into both ends of PLGA nerve conduit in the experimental group (n=55), and the mixture of DMEM and ECM in the control group (n=45). The general situation of rats was observed after operation. At 6 hours, 1 day, 3 days, 1 week, 2 weeks, 3 weeks, 4 weeks, and 6 weeks, the inflammatory cytokines were detected by Western blot. At 2, 4, and 6 weeks, the survival of GFP-OEC was observed in the experimental group. At 9 weeks, HE staining was used to observe the morphology of nerve tissue, and the sensory and motor function and the electrophysiological index were detected. Results The cultured primary cells were GFP-OECs by immunofluorescence staining. Compared with the control group, the experimental group showed significantly increased expression level of IL-4 at 2-6 weeks (P < 0.05), significantly decreased expression level of IL-6 and TNF-α at 3 days and 1 week (P < 0.05) and significantly increased expression level of IL-13 at 1 day and 3-6 weeks (P < 0.05) by Western blot detection. At 2, 4, and 6 weeks, the surviving GFP-OEC of regenerative nerve end was observed in the experimental group under the fluorescence microscope. At 9 weeks, regenerative nerve tissue was loose, and cell morphology was irregular in the experimental group, while the regenerative nerve tissue had vesicular voids and the cell number decreased significantly in the control group. At 9 weeks, the functional recovery of sciatic nerve in the experimental group was better than that of the control group, showing significant difference in the lateral foot retraction time, sciatic nerve function index, muscle action potential latency, and the amplitude of compound muscle action potential (P < 0.05). Conclusion OEC can promote the anti-inflammation cytokines expression of IL-4 and IL-13 and inhibit the pro-inflammatory cytokines expression of IL-6 and TNF-α, which can improve the local inflammatory microenvironment of sciatic nerve and effectively promote the structure and function recovery of sciatic nerve.

Citation： YAODongdong, ZHANGJieyuan, LIBingcang, ZHOUChan, LIUBin. REGULATORY EFFECT OF OLFACTORY ENSHEATHING CELLS ON INFLAMMATORY CYTOKINES IN REPAIR OF RAT SCIATIC NERVE DEFECT. Chinese Journal of Reparative and Reconstructive Surgery, 2016, 30(12): 1538-1544. doi: 10.7507/1002-1892.20160317 Copy

1.	姚东东, 张洁元, 刘彬, 等.周围神经损伤修复微环境的研究进展.中国修复重建外科杂志, 2015, 29(9):1167-1172.
2.	Cámara-Lemarroy CR, Guzmán-de la Garza FJ, Fernández-Garza NE. Molecular inflammatory mediators in peripheral nerve degeneration and regeneration. Neuroimmunomodulation, 2010, 17(5):314-324.
3.	Hendrix S, Nitsch R. The role of T helper cells in neuroprotection and regeneration. J Neuroimmunol, 2007, 184(1-2):100-112.
4.	Vidal PM, Lemmens E, Dooley D, et al. The role of "anti-inflammatory" cytokines in axon regeneration. Cytokine Growth Factor Rev, 2013, 24(1):1-12.
5.	Moghaddam A, Child C, Bruckner T, et al. Posttraumatic inflammation as a key to neuroregeneration after traumatic spinal cord injury. Int J Mol Sci, 2015, 16(4):7900-7916.
6.	刘彬, 可金星, 蔡绍皙, 等. PLGA/ECM神经支架性质的体外评价.生物工程学报, 2012, 28(3):349-357.
7.	Zhang JY, Liu Z, Chen HJ, et al. Synergic effects of EPI-NCSCs and OECs on the donor cells migration, the expression of neurotrophic factors, and locomotor recovery of contused spinal cord of rats. J Mol Neurosci, 2015, 55(3):760-769.
8.	Ekberg JA, Amaya D, Mackay-Sim A, et al. The migration of olfactory ensheathing cells during development and regeneration. Neurosignals, 2012, 20(3):147-158.
9.	Rao YJ, Zhu WX, Du ZQ, et al. Effectiveness of olfactory ensheathing cell transplantation for treatment of spinal cord injury. Genet Mol Res, 2014, 13(2):4124-4129.
10.	Radtke C, Kocsis JD. Olfactory-ensheathing cell transplantation for peripheral nerve repair:Update on recent developments. Cells Tissues Organs, 2014, 200(1):48-58.
11.	Sasaki M, Lankford KL, Zemedkun M, et al. Identified olfactory ensheathing cells transplanted into the transected dorsal funiculus bridge the lesion and form myelin. J Neurosci, 2004, 24(39):8485-8493.
12.	Sundback CA, Shyu JY, Wang Y, et al. Biocompatibility analysis of poly (glycerol sebacate) as a nerve guide material. Biomaterials, 2005, 26(27):5454-5464.
13.	Young C, Miller E, Nicklous DM, et al. Nerve growth factor and neurotrophin-3 affect functional recovery following peripheral nerve injury differently. Restor Neurol Neurosci, 2001, 18(4):167-175.
14.	Zarbakhsh S, Bakhtiyari M, Faghihi A, et al. The effects of schwann and bone marrow stromal stem cells on sciatic nerve injury in rat:a comparison of functional recovery. Cell J, 2012, 14(1):39-46.
15.	Zarbakhsh S, Moradi F, Joghataei MT, et al. Evaluation of the functional recovery in sciatic nerve injury following the co-transplantation of schwann and bone marrow stromal stem cells in rat. Basic Clin Neurosci, 2013, 4(4):291-298.
16.	Ahmed MR, Vairamuthu S, Shafiuzama M, et al. Microwave irradiated collagen tubes as a better matrix for peripheral nerve regeneration. Brain Res, 2005, 1046(1-2):55-67.
17.	Matsumoto K, Ohnishi K, Kiyotani T, et al. Peripheral nerve regeneration across an 80-mm gap bridged by a polyglycolic acid (PGA)-collagen tube filled with laminin-coated collagen fibers:a histological and electrophysiological evaluation of regenerated nerves. Brain Res, 2000, 868(2):315-328.
18.	Chuah MI, Hale DM, West AK. Interaction of olfactory ensheathing cells with other cell types in vitro and after transplantation:glial scars and inflammation. Exp Neurol, 2011, 229(1):46-53.
19.	Zhang J, Chen H, Duan Z, et al. The effects of co-transplantation of olfactory ensheathing cells and schwann cells on local inflammation environment in the contused spinal cord of rats. Mol Neurobiol, 2016.[Epub ahead of print].
20.	Omi M, Hata M, Nakamura N, et al. Transplantation of dental pulp stem cells suppressed inflammation in sciatic nerves by promoting macrophage polarization towards anti-inflammation phenotypes and ameliorated diabetic polyneuropathy. J Diabetes Investig, 2016, 7(4):485-496.
21.	Nadeau S, Filali M, Zhang J, et al. Functional recovery after peripheral nerve injury is dependent on the pro-inflammatory cytokines IL-1β and TNF:implications for neuropathic pain. J Neurosci, 2011, 31(35):12533-12542.
22.	Moghaddam A, Child C, Bruckner T, et al. Posttraumatic inflammation as a key to neuroregeneration after traumatic spinal cord injury. Int J Mol Sci, 2015, 16(4):7900-7916.
23.	Kocsis JD. Neuroprotection and immunomodulation by cell transplantation are becoming central themes in potential therapeutic approaches for cell-based therapies. Neurosci Lett, 2009, 456(3):99.
24.	You H, Wei L, Liu Y, et al. Olfactory ensheathing cells enhance Schwann cell-mediated anatomical and functional repair after sciatic nerve injury in adult rats. Exp Neurol, 2011, 229(1):158-167.

1. 姚东东, 张洁元, 刘彬, 等.周围神经损伤修复微环境的研究进展.中国修复重建外科杂志, 2015, 29(9):1167-1172.
2. Cámara-Lemarroy CR, Guzmán-de la Garza FJ, Fernández-Garza NE. Molecular inflammatory mediators in peripheral nerve degeneration and regeneration. Neuroimmunomodulation, 2010, 17(5):314-324.
3. Hendrix S, Nitsch R. The role of T helper cells in neuroprotection and regeneration. J Neuroimmunol, 2007, 184(1-2):100-112.
4. Vidal PM, Lemmens E, Dooley D, et al. The role of "anti-inflammatory" cytokines in axon regeneration. Cytokine Growth Factor Rev, 2013, 24(1):1-12.
5. Moghaddam A, Child C, Bruckner T, et al. Posttraumatic inflammation as a key to neuroregeneration after traumatic spinal cord injury. Int J Mol Sci, 2015, 16(4):7900-7916.
6. 刘彬, 可金星, 蔡绍皙, 等. PLGA/ECM神经支架性质的体外评价.生物工程学报, 2012, 28(3):349-357.
7. Zhang JY, Liu Z, Chen HJ, et al. Synergic effects of EPI-NCSCs and OECs on the donor cells migration, the expression of neurotrophic factors, and locomotor recovery of contused spinal cord of rats. J Mol Neurosci, 2015, 55(3):760-769.
8. Ekberg JA, Amaya D, Mackay-Sim A, et al. The migration of olfactory ensheathing cells during development and regeneration. Neurosignals, 2012, 20(3):147-158.
9. Rao YJ, Zhu WX, Du ZQ, et al. Effectiveness of olfactory ensheathing cell transplantation for treatment of spinal cord injury. Genet Mol Res, 2014, 13(2):4124-4129.
10. Radtke C, Kocsis JD. Olfactory-ensheathing cell transplantation for peripheral nerve repair:Update on recent developments. Cells Tissues Organs, 2014, 200(1):48-58.
11. Sasaki M, Lankford KL, Zemedkun M, et al. Identified olfactory ensheathing cells transplanted into the transected dorsal funiculus bridge the lesion and form myelin. J Neurosci, 2004, 24(39):8485-8493.
12. Sundback CA, Shyu JY, Wang Y, et al. Biocompatibility analysis of poly (glycerol sebacate) as a nerve guide material. Biomaterials, 2005, 26(27):5454-5464.
13. Young C, Miller E, Nicklous DM, et al. Nerve growth factor and neurotrophin-3 affect functional recovery following peripheral nerve injury differently. Restor Neurol Neurosci, 2001, 18(4):167-175.
14. Zarbakhsh S, Bakhtiyari M, Faghihi A, et al. The effects of schwann and bone marrow stromal stem cells on sciatic nerve injury in rat:a comparison of functional recovery. Cell J, 2012, 14(1):39-46.
15. Zarbakhsh S, Moradi F, Joghataei MT, et al. Evaluation of the functional recovery in sciatic nerve injury following the co-transplantation of schwann and bone marrow stromal stem cells in rat. Basic Clin Neurosci, 2013, 4(4):291-298.
16. Ahmed MR, Vairamuthu S, Shafiuzama M, et al. Microwave irradiated collagen tubes as a better matrix for peripheral nerve regeneration. Brain Res, 2005, 1046(1-2):55-67.
17. Matsumoto K, Ohnishi K, Kiyotani T, et al. Peripheral nerve regeneration across an 80-mm gap bridged by a polyglycolic acid (PGA)-collagen tube filled with laminin-coated collagen fibers:a histological and electrophysiological evaluation of regenerated nerves. Brain Res, 2000, 868(2):315-328.
18. Chuah MI, Hale DM, West AK. Interaction of olfactory ensheathing cells with other cell types in vitro and after transplantation:glial scars and inflammation. Exp Neurol, 2011, 229(1):46-53.
19. Zhang J, Chen H, Duan Z, et al. The effects of co-transplantation of olfactory ensheathing cells and schwann cells on local inflammation environment in the contused spinal cord of rats. Mol Neurobiol, 2016.[Epub ahead of print].
20. Omi M, Hata M, Nakamura N, et al. Transplantation of dental pulp stem cells suppressed inflammation in sciatic nerves by promoting macrophage polarization towards anti-inflammation phenotypes and ameliorated diabetic polyneuropathy. J Diabetes Investig, 2016, 7(4):485-496.
21. Nadeau S, Filali M, Zhang J, et al. Functional recovery after peripheral nerve injury is dependent on the pro-inflammatory cytokines IL-1β and TNF:implications for neuropathic pain. J Neurosci, 2011, 31(35):12533-12542.
22. Moghaddam A, Child C, Bruckner T, et al. Posttraumatic inflammation as a key to neuroregeneration after traumatic spinal cord injury. Int J Mol Sci, 2015, 16(4):7900-7916.
23. Kocsis JD. Neuroprotection and immunomodulation by cell transplantation are becoming central themes in potential therapeutic approaches for cell-based therapies. Neurosci Lett, 2009, 456(3):99.
24. You H, Wei L, Liu Y, et al. Olfactory ensheathing cells enhance Schwann cell-mediated anatomical and functional repair after sciatic nerve injury in adult rats. Exp Neurol, 2011, 229(1):158-167.

Chinese Journal of Reparative and Reconstructive Surgery

REGULATORY EFFECT OF OLFACTORY ENSHEATHING CELLS ON INFLAMMATORY CYTOKINES IN REPAIR OF RAT SCIATIC NERVE DEFECT

Abstract Full text Figures/Tables Video References Cited by

Previous Article

Next Article

Format

Content