Effect of combination of acellular nerve grafts and stem cells for sciatic nerve regeneration: a Meta-analysis

doi:10.3969/j.issn.2095-4344.2017.22.026

Abstract

Abstract:

BACKGROUND: Acellular nerve scaffolds have the three-dimensional structure of natural nerves and low immunogenicity, but their effect on long nerve defects is still not ideal. Therefore, it is necessary to construct tissue- engineered nerve using acellular nerve and seed cells in order to improve the therapeutic effect.

OBJECTIVE: To systemically review the efficacy of combination of acellular nerve grafts (ANGs) and mesenchymal stem cells (MSCs) or Schwann cells (SCs) transplantation in the treatment of sciatic nerve defects in a rat model.

METHODS: Randomized controlled trials (RCTs) about the effects of combination of ANGs and MSCs or SCs transplantation for sciatic nerve defects in rats were searched in PubMed, The Cochrane Library, EMbase, CNKI, WanFang and VIP from inception to July 2016. Three reviewers independently screened literature according to the inclusion and exclusion criteria, extracted data, and assessed the risk of bias of included studies. Then, a Meta-analysis was performed using Review Manger5.3 software.

RESULTS AND CONCLUSION: A total of 10 RCTs involving 252 rats were included. The results of meta-analysis showed that: compared with the control group (simple acellular nerve scaffold group), the sciatic functional index (SFI) of the combined group (combination of ANGs and MSCs or SCs transplantation) were superior at 2 weeks [SMD=2.73, 95% CI (1.92, 3.45), P < 0.000 01], 4 weeks [SMD=4.57, 95% CI (3.43, 5.70), P < 0.000 01], 6 weeks [SMD=1.62, 95% CI (0.18,3.06), P=0.03], 8 weeks [SMD=4.90, 95% CI (2.96, 6.84), P < 0.000 01] after surgery. The nerve conduction velocity [SMD=1.39, 95% CI (0.99, 1.78), P < 0.000 01), latency period (MD=-0.98, 95% CI (-1.19, -0.76), P < 0.000 01], and amplitude [SMD=1.23, 95% CI (0.62, 1.85), P < 0.000 1] were superior at 12 weeks after surgery. The myelin sheath thickness was superior at 8 weeks [MD=0.14, 95% CI (0.07, 0.21), P < 0.000 1], 12 weeks [SMD=1.85, 95% CI (1.63, 2.08), P < 0.000 01] and the number of myelinated nerve fibers were superior at 12 weeks [SMD=3.59, 95%CI (2.63, 4.55), P < 0.000 01] after surgery. The gastrocnemius wet weight was superior at 8 weeks after surgery [SMD=4.22, 95% CI (2.40, 6.03), P < 0.000 01]. Current evidence indicates that the combination of ANGs and MSCs or SCs can promote the regeneration and functional recovery of the peripheral nerve. Due to the limited quality of the included studies, the above conclusion should be verified by conducting high-quality and large-scale RCTs.

中国组织工程研究杂志出版内容重点：生物材料；骨生物材料; 口腔生物材料; 纳米材料; 缓释材料; 材料相容性；组织工程

Key words: Peripheral Nerves, Schwann Cells, Mesenchymal Stem Cells, Tissue Engineering

CLC Number:

R318

Xiang Fei-fan, Yang Yun-kang, Tan Xiao-qi, Wei Dai-qing, Yang Kun, Sun Yuan-lin, Zhou Ju.

Effect of combination of acellular nerve grafts and stem cells for sciatic nerve regeneration: a Meta-analysis

[J]. Chinese Journal of Tissue Engineering Research, 2017, 21(22): 3602-3608.

Figures/Tables 6

References

[1]Isaacs J. Major peripheral nerve injuries. Hand Clin. 2013; 29(3):371-382.

[2]Sachanandani NF, Pothula A, Tung TH. Nerve gaps. Plast Reconstr Surg. 2014;133(2):313-319.

[3]Isaacs J, Browne T. Overcoming short gaps in peripheral nerve repair: conduits and human acellular nerve allograft. Hand (N Y). 2014;9(2):131-137.

[4]He B, Zhu Q, Chai Y, et al. Safety and efficacy evaluation of a human acellular nerve graft as a digital nerve scaffold: a prospective, multicentre controlled clinical trial. J Tissue Eng Regen Med. 2015;9(3):286-295.

[5]Zhu S, Liu J, Zheng C, et al. Analysis of human acellular nerve allograft reconstruction of 64 injured nerves in the hand and upper extremity: a 3 year follow-up study. J Tissue Eng Regen Med. 2016 Apr 21. [Epub ahead of print]

[6]Fan L, Yu Z, Li J, et al. Schwann-like cells seeded in acellular nerve grafts improve nerve regeneration. BMC Musculoskelet Disord. 2014;15:165.

[7]Santosa KB, Jesuraj NJ, Viader A, et al. Nerve allografts supplemented with schwann cells overexpressing glial-cell-line-derived neurotrophic factor. Muscle Nerve. 2013;47(2):213-223.

[8]Zhou LN, Zhang JW, Liu XL, et al. Co-Graft of Bone Marrow Stromal Cells and Schwann Cells Into Acellular Nerve Scaffold for Sciatic Nerve Regeneration in Rats. J Oral Maxillofac Surg. 2015;73(8):1651-1660.

[9]Zhang YR, Ka K, Zhang GC, et al. Repair of peripheral nerve defects with chemically extracted acellular nerve allografts loaded with neurotrophic factors-transfected bone marrow mesenchymal stem cells. Neural Regen Res. 2015;10(9):1498-1506.

[10]Wang X, Wang S, Xiao Y. An experimental study on repair of sciatic nerve injury by schwann-like cells derived from umbilical cord blood mesenchymal stem cells. Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi. 2015;29(2):213-220.

[11]Zhang Y, Zhang H, Zhang G, 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.

[12]Gao S, Zheng Y, Cai Q, et al. Combination of acellular nerve graft and schwann cells-like cells for rat sciatic nerve regeneration.Neural Plast. 2014;2014:139085.

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

[14]Liu G, Cheng Y, Guo S, et al. Transplantation of adipose-derived stem cells for peripheral nerve repair. Int J Mol Med. 2011;28(4):565-572.

[15]Zhao Z, Zhao B, Wang Y, et al. Functional evaluation of chemically extracted acellular nerve allograft supplement with different tissues of Schwann cells for peripheral nerve regeneration. Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi. 2010;24(11):1281-1287.

[16]Sun XH, Che YQ, Tong XJ, et al. Improving nerve regeneration of acellular nerve allografts seeded with SCs bridging the sciatic nerve defects of rat. Cell Mol Neurobiol. 2009;29(3):347-353.

[17]Wei AL, Liu SQ, Tao HY, et al. Repairing peripheral nerve defects with tissue engineered artificial nerves in rats. Chin J Traumatol. 2008;11(1):28-33.

[18]Lin MY, Manzano G, Gupta R. Nerve allografts and conduits in peripheral nerve repair. Hand Clin. 2013;29(3):331-348.

[19]Sridharan R, Reilly RB, Buckley CT. Decellularized grafts with axially aligned channels for peripheral nerve regeneration. J Mech Behav Biomed Mater. 2015;41:124-135.

[20]Sullivan R, Dailey T, Duncan K, et al. Peripheral Nerve Injury: Stem Cell Therapy and Peripheral Nerve Transfer. Int J Mol Sci. 2016;17(12): E2101.

[21]Goulart CO, Jürgensen S, Souto A, et al. A combination of Schwann-cell grafts and aerobic exercise enhances sciatic nerve regeneration. PLoS One. 2014;9(10):e110090.

[22]Xiang F, Wei D, Yang Y, et al. Tissue-engineered nerve graft with tetramethylpyrazine for repair of sciatic nerve defects in rats. Neurosci Lett. 2017;638:114-120.

[23]Jiang CQ, Hu J, Xiang JP, et al. Tissue-engineered rhesus monkey nerve grafts for the repair of long ulnar nerve defects: similar outcomes to autologous nerve grafts. Neural Regen Res. 2016;11(11):1845-1850.

[24]García-Pérez MM, Martínez-Rodríguez HG, López-Guerra GG, et al. A modified chemical protocol of decellularization of rat sciatic nerve and its recellularization with mesenchimal differentiated schwann-like cells: morphological and functional assessments. Histol Histopathol. 2016 Nov 18. [Epub ahead of print]