Skip to main content
SpringerLink
Log in

Olfactory-ensheathing cells promote physiological repair of injured recurrent laryngeal nerves and functional recovery of glottises in dogs

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

The aim of this study was to investigate whether the transplantation of olfactory-ensheathing cells (OECs) could physiologically repair severely injured recurrent laryngeal nerve (RLN) in dogs. Adult Beagle dogs were surgically introduced with a 10-mm defect in the left RLN and transplanted with a nerve guide (NEUROLAC) containing dog olfactory mucosa-olfactory-ensheathing cells (OM-OECs) in matrigel. The effects of OM-OECs on the morphology, histology, and electrophysiology of the injured RLNs, glottis movement, and voice acoustics were comparatively studied. Two months after transplantation, the normal dogs (group N) had intact left RLNs that contained axons well organized as bundles, transmitted action potentials of high amplitudes without latent phases, and modulated glottis movement to produce normal voices. The RLN-damaged dogs transplanted with OM-OECs (group CTT) had pieces of nerves regenerated in the place of the defects, which contained fewer axons scattered in the internal nerve membrane and wrapped peripherally by the connective tissue, prevented the distal trunk of the defected RLN from shrinking, transmitted action potentials of lower amplitudes with latent phases, and modulated a slightly impaired glottis movement to produce voices with slight differences compared to the N dogs. The RLN-damaged dogs without OM-OECs (group NC) had no nerves generated at the defective or the damaged area, leading to a shrinkage in the enervated distal nerve trunks; a blockage in nerve pulse transit; a paralysis of the left vocal cords; an impaired glottis movement; and abnormal voices. Transplantation of OM-OECs promoted nerve regeneration, and the recoveries of glottises and voices in dogs with RLN injury.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

References

  1. Haller JM, Iwanik M, Shen FH (2012) Clinically relevant anatomy of recurrent laryngeal nerve. Spine (Phila Pa 1976) 37:97–100. https://doi.org/10.1097/BRS.0b013e31821f3e86

    Article  Google Scholar 

  2. Hayward NJ, Grodski S, Yeung M, Johnson WR, Serpell J (2013) Recurrent laryngeal nerve injury in thyroid surgery: a review. ANZ J Surg 83:15–21. https://doi.org/10.1111/j.1445-2197.2012.06247.x

    Article  PubMed  Google Scholar 

  3. Jiang Y, Gao B, Zhang X, Zhao J, Chen J, Zhang S, Luo D (2014) Prevention and treatment of recurrent laryngeal nerve injury in thyroid surgery. Int J Clin Exp Med 7:101–107

    PubMed  PubMed Central  Google Scholar 

  4. Alfares FA, Hynes CF, Ansari G, Chounoune R, Ramadan M, Shaughnessy C, Reilly BK, Zurakowski D, Jonas RA, Nath DS (2016) Outcomes of recurrent laryngeal nerve injury following congenital heart surgery: a contemporary experience. J Saudi Heart Assoc 28:1–6. https://doi.org/10.1016/j.jsha.2015.05.002

    Article  PubMed  Google Scholar 

  5. Tuzuner A (2014) Recurrent laryngeal nerve palsy following blunt trauma of lateral neck. Austin J Surg 1:1021

    Google Scholar 

  6. Hermann M, Alk G, Roka R, Glaser K, Freissmuth M (2002) Laryngeal recurrent nerve injury in surgery for benign thyroid diseases: effect of nerve dissection and impact of individual surgeon in more than 27,000 nerves at risk. Ann Surg 235:261–268

    Article  PubMed  PubMed Central  Google Scholar 

  7. Joliat GR, Guarnero V, Demartines N, Schweizer V, Matter M (2017) Recurrent laryngeal nerve injury after thyroid and parathyroid surgery: Incidence and postoperative evolution assessment. Medicine (Baltimore) 96:e6674. https://doi.org/10.1097/MD.0000000000006674

    Article  Google Scholar 

  8. Gillig PM, Sanders RD (2010) Cranial nerves IX, X, XI, and XII. Psychiatry (Edgmont) 7:37–41

    Google Scholar 

  9. Zabrodsky M, Boucek J, Kastner J, Kuchar M, Chovanec M, Betka J (2012) Immediate revision in patients with bilateral recurrent laryngeal nerve palsy after thyroid and parathyroid surgery. How worthy is it? Acta Otorhinolaryngol Ital 32:222–228

    PubMed  PubMed Central  CAS  Google Scholar 

  10. Lynch J, Parameswaran R (2017) Management of unilateral recurrent laryngeal nerve injury after thyroid surgery: a review. Head Neck 39:1470–1478. https://doi.org/10.1002/hed.24772

    Article  PubMed  Google Scholar 

  11. Wen W, Zhou SM, Li ZJ (1999) [Repair of recurrent laryngeal nerve injuries after thyroidectomy]. Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi 13:217–219

    PubMed  CAS  Google Scholar 

  12. van Lith-Bijl JT, Stolk RJ, Tonnaer JA, Groenhout C, Konings PN, Mahieu HF (1997) Selective laryngeal reinnervation with separate phrenic and ansa cervicalis nerve transfers. Arch Otolaryngol Head Neck Surg 123:406–411

    Article  PubMed  Google Scholar 

  13. Kanemaru S, Nakamura T, Omori K, Kojima H, Magrufov A, Hiratsuka Y, Ito J, Shimizu Y (2003) Recurrent laryngeal nerve regeneration by tissue engineering. Ann Otol Rhinol Laryngol 112:492–498. https://doi.org/10.1177/000348940311200602

    Article  PubMed  Google Scholar 

  14. Chambers KJ, Raol N, Song PC, Randolph GW, Hartnick CJ (2015) Laryngeal reinnervation using a split-hypoglossal nerve graft in a canine model. JAMA Otolaryngol Head Neck Surg 141:620–627. https://doi.org/10.1001/jamaoto.2015.0929

    Article  PubMed  Google Scholar 

  15. Zheng Z, Liu G, Chen Y, Wei S (2013) Olfactory ensheathing cell transplantation improves sympathetic skin responses in chronic spinal cord injury. Neural Regen Res 8:2849–2855. https://doi.org/10.3969/j.issn.1673-5374.2013.30.007

    Article  PubMed  PubMed Central  Google Scholar 

  16. Raisman G, Li Y (2007) Repair of neural pathways by olfactory ensheathing cells. Nat Rev Neurosci 8:312–319. https://doi.org/10.1038/nrn2099

    Article  PubMed  CAS  Google Scholar 

  17. Radtke C, Kocsis JD (2012) Peripheral nerve injuries and transplantation of olfactory ensheathing cells for axonal regeneration and remyelination: fact or fiction? Int J Mol Sci 13:12911–12924. https://doi.org/10.3390/ijms131012911

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  18. Radtke C, Kocsis JD (2014) Olfactory-ensheathing cell transplantation for peripheral nerve repair: update on recent developments. Cells Tissues Organs 200:48–58. https://doi.org/10.1159/000369006

    Article  PubMed  CAS  Google Scholar 

  19. de Corgnol AC, Guerout N, Duclos C, Verin E, Marie JP (2011) Olfactory ensheathing cells in a rat model of laryngeal reinnervation. Ann Otol Rhinol Laryngol 120:273–280. https://doi.org/10.1177/000348941112000410

    Article  PubMed  Google Scholar 

  20. Guerout N, Paviot A, Bon-Mardion N, Duclos C, Genty D, Jean L, Boyer O, Marie JP (2011) Co-transplantation of olfactory ensheathing cells from mucosa and bulb origin enhances functional recovery after peripheral nerve lesion. PLoS ONE 6:e22816. https://doi.org/10.1371/journal.pone.0022816

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  21. Guerout N, Paviot A, Bon-Mardion N, Honore A, Obongo R, Duclos C, Marie JP (2014) Transplantation of olfactory ensheathing cells to evaluate functional recovery after peripheral nerve injury. J Vis Exp. https://doi.org/10.3791/50590

    Article  PubMed  PubMed Central  Google Scholar 

  22. Roloff F, Ziege S, Baumgartner W, Wewetzer K, Bicker G (2013) Schwann cell-free adult canine olfactory ensheathing cell preparations from olfactory bulb and mucosa display differential migratory and neurite growth-promoting properties in vitro. BMC Neurosci 14:141. https://doi.org/10.1186/1471-2202-14-141

    Article  PubMed  PubMed Central  Google Scholar 

  23. Zhu S, Ge J, Wang Y, Qi F, Ma T, Wang M, Yang Y, Liu Z, Huang J, Luo Z (2014) A synthetic oxygen carrier-olfactory ensheathing cell composition system for the promotion of sciatic nerve regeneration. Biomaterials 35:1450–1461. https://doi.org/10.1016/j.biomaterials.2013.10.071

    Article  PubMed  CAS  Google Scholar 

  24. Fischer AH, Jacobson KA, Rose J, Zeller R (2008) Hematoxylin and eosin staining of tissue and cell sections. CSH Protoc. https://doi.org/10.1101/pdb.prot4986

    Article  PubMed  Google Scholar 

  25. Sridharan G, Shankar AA (2012) Toluidine blue: A review of its chemistry and clinical utility. J Oral Maxillofac Pathol 16:251–255. https://doi.org/10.4103/0973-029X.99081

    Article  PubMed  PubMed Central  Google Scholar 

  26. Imaizumi T, Lankford KL, Waxman SG, Greer CA, Kocsis JD (1998) Transplanted olfactory ensheathing cells remyelinate and enhance axonal conduction in the demyelinated dorsal columns of the rat spinal cord. J Neurosci 18:6176–6185

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  27. Chiu SC, Hung HS, Lin SZ, Chiang E, Liu DD (2009) Therapeutic potential of olfactory ensheathing cells in neurodegenerative diseases. J Mol Med (Berlin) 87:1179–1189. https://doi.org/10.1007/s00109-009-0528-2

    Article  Google Scholar 

  28. Daly W, Yao L, Zeugolis D, Windebank A, Pandit A (2012) A biomaterials approach to peripheral nerve regeneration: bridging the peripheral nerve gap and enhancing functional recovery. J R Soc Interface 9:202–221. https://doi.org/10.1098/rsif.2011.0438

    Article  PubMed  CAS  Google Scholar 

  29. Schmidt CE, Leach JB (2003) Neural tissue engineering: strategies for repair and regeneration. Annu Rev Biomed Eng 5:293–347. https://doi.org/10.1146/annurev.bioeng.5.011303.120731

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

This work was funded by the Foundation for Military Medicine, China (BWS11J035) and Key Disciplines Group Construction Project of Pudong Health Bureau of Shanghai (PWZxq2017-04).

Author information

Author notes

    Authors and Affiliations

    1. Department of Otolaryngology Head and Neck Surgery, Changzheng Hospital, Second Military Medical University, No. 415 Fengyang Road, Shanghai, 200003, China

      Hongyi Liu, Yu Pu, Yaping Xu, He Xu, Huanhai Liu, Yin Cheng & Jingping Fan

    2. Department of Otolaryngology Head and Neck Surgery, Gongli Hospital, Second Military Medical University, Shanghai, 200135, China

      Weihua Xu & Xiaoping Chen

    Authors
    1. Hongyi Liu
      View author publications

      You can also search for this author in PubMed Google Scholar

    2. Yu Pu
      View author publications

      You can also search for this author in PubMed Google Scholar

    3. Yaping Xu
      View author publications

      You can also search for this author in PubMed Google Scholar

    4. He Xu
      View author publications

      You can also search for this author in PubMed Google Scholar

    5. Huanhai Liu
      View author publications

      You can also search for this author in PubMed Google Scholar

    6. Yin Cheng
      View author publications

      You can also search for this author in PubMed Google Scholar

    7. Weihua Xu
      View author publications

      You can also search for this author in PubMed Google Scholar

    8. Xiaoping Chen
      View author publications

      You can also search for this author in PubMed Google Scholar

    9. Jingping Fan
      View author publications

      You can also search for this author in PubMed Google Scholar

    Corresponding authors

    Correspondence to Xiaoping Chen or Jingping Fan.

    Ethics declarations

    Conflict of interest

    All the authors declare that they have no conflict of interest.

    Additional information

    Hongyi Liu and Yu Pu contributed equally to this work.

    Rights and permissions

    Reprints and permissions

    About this article

    Check for updates. Verify currency and authenticity via CrossMark

    Cite this article

    Liu, H., Pu, Y., Xu, Y. et al. Olfactory-ensheathing cells promote physiological repair of injured recurrent laryngeal nerves and functional recovery of glottises in dogs. Mol Cell Biochem 446, 115–125 (2018). https://doi.org/10.1007/s11010-018-3279-y

    Download citation

    • Received:

    • Accepted:

    • Published:

    • Issue Date:

    • DOI: https://doi.org/10.1007/s11010-018-3279-y

    Keywords

    Search

    Navigation