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Neural Stem Cells Enhance Nerve Regeneration after Sciatic Nerve Injury in Rats

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Abstract

With the development of tissue engineering and the shortage of autologous nerve grafts in nerve reconstruction, cell transplantation in a conduit is an alternative strategy to improve nerve regeneration. The present study evaluated the effects and mechanism of brain-derived neural stem cells (NSCs) on sciatic nerve injury in rats. At the transection of the sciatic nerve, a 10-mm gap between the nerve stumps was bridged with a silicon conduit filled with 5 × 105 NSCs. In control experiments, the conduit was filled with nerve growth factor (NGF) or normal saline (NS). The functional and morphological properties of regenerated nerves were investigated, and expression of hepatocyte growth factor (HGF) and NGF was measured. One week later, there was no connection through the conduit. Four or eight weeks later, fibrous connections were evident between the proximal and distal segments. Motor function was revealed by measurement of the sciatic functional index (SFI) and sciatic nerve conduction velocity (NCV). Functional recovery in the NSC and NGF groups was significantly more advanced than that in the NS group. NSCs showed significant improvement in axon myelination of the regenerated nerves. Expression of NGF and HGF in the injured sciatic nerve was significantly lower in the NS group than in the NSCs and NGF groups. These results and other advantages of NSCs, such as ease of harvest and relative abundance, suggest that NSCs could be used clinically to enhance peripheral nerve repair.

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References

  1. Whitlock EL, Tuffaha SH, Luciano JP, Yan Y, Hunter DA, Magill CK, Moore AM, Tong AY, Mackinnon SE, Borschel GH (2009) Processed allografts and type I collagen conduits for repair of peripheral nerve gaps. Muscle Nerve 39:787–799

    Article  PubMed  CAS  Google Scholar 

  2. Lundborg G (2003) Richard P. Bunge memorial lecture. Nerve injury and repair—a challenge to the plastic brain. J Peripher Nerv Syst 8:209–226

    Article  PubMed  Google Scholar 

  3. Udina E, Ceballos D, Gold BG, Navarro X (2003) FK506 enhances reinnervation by regeneration and by collateral sprouting of peripheral nerve fibers. Exp Neurol 183:220–231

    Article  PubMed  CAS  Google Scholar 

  4. Fatemi MJ, Foroutan KS, Ashtiani AK, Mansoori MJ, Vaghardoost R, Pedram S, Hosseinpolli A, Rajabi F, Mousavi SJ (2010) Comparison of divided sciatic nerve growth within dermis, venous and nerve graft conduit in rat. J Res Med Sci 15:208–213

    PubMed  Google Scholar 

  5. Pfister LA, Papaloizos M, Merkle HP, Gander B (2007) Nerve conduits and growth factor delivery in peripheral nerve repair. J Peripher Nerv Syst 12:65–82

    Article  PubMed  CAS  Google Scholar 

  6. Zhang Y, Luo H, Zhang Z, Lu Y, Huang X, Yang L, Xu J, Yang W, Fan X, Du B, Gao P, Hu G, Jin Y (2010) A nerve graft constructed with xenogeneic acellular nerve matrix and autologous adipose-derived mesenchymal stem cells. Biomaterials 31:5312–5324

    Article  PubMed  CAS  Google Scholar 

  7. Nectow AR, Marra KG, Kaplan DL (2011) Biomaterials for the development of peripheral nerve guidance conduits. Tissue Eng Part B Rev 18:40–50

    Article  PubMed  Google Scholar 

  8. Mohanna PN, Terenghi G, Wiberg M (2005) Composite PHB–GGF conduit for long nerve gap repair: a long-term evaluation. Scand J Plast Reconstr Surg Hand Surg 39:129–137

    Article  PubMed  Google Scholar 

  9. Belkas JS, Shoichet MS, Midha R (2004) Peripheral nerve regeneration through guidance tubes. Neurol Res 26:151–160

    Article  PubMed  Google Scholar 

  10. Hall S (1997) Axonal regeneration through acellular muscle grafts. J Anat 190(Pt 1):57–71

    Article  PubMed  Google Scholar 

  11. Chalfoun CT, Wirth GA, Evans GR (2006) Tissue engineered nerve constructs: where do we stand? J Cell Mol Med 10:309–317

    Article  PubMed  CAS  Google Scholar 

  12. Krick K, Tammia M, Martin R, Hoke A, Mao HQ (2011) Signaling cue presentation and cell delivery to promote nerve regeneration. Curr Opin Biotechnol 22:741–746

    Article  PubMed  CAS  Google Scholar 

  13. Terenghi G (1995) Peripheral nerve injury and regeneration. Histol Histopathol 10:709–718

    PubMed  CAS  Google Scholar 

  14. Mirsky R, Jessen KR, Brennan A, Parkinson D, Dong Z, Meier C, Parmantier E, Lawson D (2002) Schwann cells as regulators of nerve development. J Physiol Paris 96:17–24

    Article  PubMed  CAS  Google Scholar 

  15. Guenard V, Kleitman N, Morrissey TK, Bunge RP, Aebischer P (1992) Syngeneic Schwann cells derived from adult nerves seeded in semipermeable guidance channels enhance peripheral nerve regeneration. J Neurosci 12:3310–3320

    PubMed  CAS  Google Scholar 

  16. Mosahebi A, Woodward B, Wiberg M, Martin R, Terenghi G (2001) Retroviral labeling of Schwann cells: in vitro characterization and in vivo transplantation to improve peripheral nerve regeneration. Glia 34:8–17

    Article  PubMed  CAS  Google Scholar 

  17. Rodriguez AM, Pisani D, Dechesne CA, Turc-Carel C, Kurzenne JY, Wdziekonski B, Villageois A, Bagnis C, Breittmayer JP, Groux H, Ailhaud G, Dani C (2005) Transplantation of a multipotent cell population from human adipose tissue induces dystrophin expression in the immunocompetent mdx mouse. J Exp Med 201:1397–1405

    Article  PubMed  CAS  Google Scholar 

  18. Barry FP, Murphy JM (2004) Mesenchymal stem cells: clinical applications and biological characterization. Int J Biochem Cell Biol 36:568–584

    Article  PubMed  CAS  Google Scholar 

  19. Gardner RL (2007) Stem cells and regenerative medicine: principles, prospects and problems. C R Biol 330:465–473

    Article  PubMed  CAS  Google Scholar 

  20. di Summa PG, Kingham PJ, Raffoul W, Wiberg M, Terenghi G, Kalbermatten DF (2010) Adipose-derived stem cells enhance peripheral nerve regeneration. J Plast Reconstr Aesthet Surg 63:1544–1552

    Article  PubMed  Google Scholar 

  21. Koka R, Hadlock TA (2001) Quantification of functional recovery following rat sciatic nerve transection. Exp Neurol 168:192–195

    Article  PubMed  CAS  Google Scholar 

  22. Shen N, Zhu J (1995) Application of sciatic functional index in nerve functional assessment. Microsurgery 16:552–555

    Article  PubMed  CAS  Google Scholar 

  23. Yao H-P, Feng W-Y, Wei Y-X, Dong H-Y (2011) Methodology of the determination of sciatic nerve conduction velocity in rats. J China Pharm 22:18–20

    Google Scholar 

  24. Weber RV, Mackinnon SE (2005) Bridging the neural gap. Clin Plast Surg 32:605–616, viii

    Article  PubMed  Google Scholar 

  25. Moldovan M, Sorensen J, Krarup C (2006) Comparison of the fastest regenerating motor and sensory myelinated axons in the same peripheral nerve. Brain 129:2471–2483

    Article  PubMed  Google Scholar 

  26. Johnson EO, Soucacos PN (2008) Nerve repair: experimental and clinical evaluation of biodegradable artificial nerve guides. Injury 39(Suppl 3):S30–S36

    Article  PubMed  Google Scholar 

  27. Chen ZL, Yu WM, Strickland S (2007) Peripheral regeneration. Annu Rev Neurosci 30:209–233

    Article  PubMed  Google Scholar 

  28. Vargas ME, Barres BA (2007) Why is Wallerian degeneration in the CNS so slow? Annu Rev Neurosci 30:153–179

    Article  PubMed  CAS  Google Scholar 

  29. Pierucci A, de Duek EA, de Oliveira AL (2008) Peripheral nerve regeneration through biodegradable conduits prepared using solvent evaporation. Tissue Eng Part A 14:595–606

    Article  PubMed  CAS  Google Scholar 

  30. di Summa PG, Kalbermatten DF, Pralong E, Raffoul W, Kingham PJ, Terenghi G (2011) Long-term in vivo regeneration of peripheral nerves through bioengineered nerve grafts. Neuroscience 181:278–291

    Article  PubMed  Google Scholar 

  31. Cui L, Jiang J, Wei L, Zhou X, Fraser JL, Snider BJ, Yu SP (2008) Transplantation of embryonic stem cells improves nerve repair and functional recovery after severe sciatic nerve axotomy in rats. Stem Cells 26:1356–1365

    Article  PubMed  CAS  Google Scholar 

  32. Hirouchi M, Ukai Y (2002) Current state on development of neuroprotective agents for cerebral ischemia. Nihon Yakurigaku Zasshi 120:107–113

    Article  PubMed  CAS  Google Scholar 

  33. Reynolds BA, Weiss S (1992) Generation of neurons and astrocytes from isolated cells of the adult mammalian central nervous system. Science 255:1707–1710

    Article  PubMed  CAS  Google Scholar 

  34. Sofroniew MV, Howe CL, Mobley WC (2001) Nerve growth factor signaling, neuroprotection, and neural repair. Annu Rev Neurosci 24:1217–1281

    Article  PubMed  CAS  Google Scholar 

  35. Yamauchi J, Miyamoto Y, Hamasaki H, Sanbe A, Kusakawa S, Nakamura A, Tsumura H, Maeda M, Nemoto N, Kawahara K, Torii T, Tanoue A (2011) The atypical guanine-nucleotide exchange factor, dock7, negatively regulates Schwann cell differentiation and myelination. J Neurosci 31:12579–12592

    Article  PubMed  CAS  Google Scholar 

  36. Udina E, Cobianchi S, Allodi I, Navarro X (2011) Effects of activity-dependent strategies on regeneration and plasticity after peripheral nerve injuries. Ann Anat 193:347–353

    Article  PubMed  CAS  Google Scholar 

  37. Zheng LF, Wang R, Yu QP, Wang H, Yi XN, Wang QB, Zhang JW, Zhang GX, Xu YZ (2010) Expression of HGF/c-Met is dynamically regulated in the dorsal root ganglions and spinal cord of adult rats following sciatic nerve ligation. Neurosignals 18:49–56

    Article  PubMed  CAS  Google Scholar 

  38. Nagayama T, Nagayama M, Kohara S, Kamiguchi H, Shibuya M, Katoh Y, Itoh J, Shinohara Y (2004) Post-ischemic delayed expression of hepatocyte growth factor and c-Met in mouse brain following focal cerebral ischemia. Brain Res 999:155–166

    Article  PubMed  CAS  Google Scholar 

  39. Shimamura M, Sato N, Sata M, Wakayama K, Ogihara T, Morishita R (2007) Expression of hepatocyte growth factor and c-Met after spinal cord injury in rats. Brain Res 1151:188–194

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

This work was supported by the Taishan Scholar with affiliation of Otology and Neuroscience Center of BMU, the program of National Natural Science Foundation of China (No. 81171142), New Century Excellent Talents in Universities (No. NCET-08-0876), the Natural Science Foundation of Shandong (No. Y2008C18), the Science and Technology Development Project of Binzhou Medical College (No. BY2008KJ25), the Science and Technology Development Project of Yantai (No. 2011073), the Medical Science and Technology Development Project of Shandong (No. 2009HW007) to F.H., and Taishan Scholar to Q.Y.Z. We thank Dr. Cindy Benedict-Alderfer for editing this manuscript.

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The authors declare that they have no conflict of interest, personally, professionally, or financially, relating to the publication of this work.

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Correspondence to Qian Liu or Fei Huang.

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Lin Xu and Shuai Zhou contributed equally to this article.

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Xu, L., Zhou, S., Feng, GY. et al. Neural Stem Cells Enhance Nerve Regeneration after Sciatic Nerve Injury in Rats. Mol Neurobiol 46, 265–274 (2012). https://doi.org/10.1007/s12035-012-8292-7

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  • DOI: https://doi.org/10.1007/s12035-012-8292-7

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