Object: The inability of the spinal cord to regenerate after
SCI is due to the extremely limited regenerative capacity of most central nervous
system (CNS) axons, along with the hostile environment of the adult CNS, which does
not support axonal growth. It seems that for successful axonal regeneration to take
place, a supportive local environment is required after the injury. We have previously
reported that transplantation of the olfactory mucosa is effective in restoring
functional recovery in rats following spinal cord transaction.
In this study, we examined histological features of olfactory mucosa grafts in rats
subjected to a spinal cord contusion protocol. Respiratory mucosa was utilized as
a control, as we have previously found that respiratory mucosa does not support
neuronal generation. Methods: The rats spinal
cords were crash-injured by dropping a 10-g metal rod from a height of 7.5 cm, and
a couple of weeks later, the injury sites were exposed, and both olfactory and respiratory
mucosae were inserted into the posterior sulcuses of the spinal cord. The each number
of olfactory and mucosa transplanted rats were five. The Basso, Beattie, and Bresnahan
(BBB) score was observed. Immunohistochemical study for neurofilament was performed. Results: Olfactory mucosa transplanted rats following spinal
cord injury can support at least partial hind limb motor recovery compared with
respiratory mucosa transplanted rats and
we identified numerous axons surrounding the transplanted olfactory mucosa cells,
and penetrating the olfactory mucosa at the transplant site. Conclusion: Olfactory mucosa
might be a suitable scaffold for axonal regeneration.
Cite this paper
K. Iwatsuki, T. Yoshimine, Y. Sankai, M. Umegaki, Y. Ohnishi, M. Ishihara, T. Moriwaki and N. Oda, "Transplantation of Olfactory Mucosa as a Scaffold for Axonal Regeneration Following Spinal Cord Contusion in Rats," Neuroscience and Medicine, Vol. 4 No. 2, 2013, pp. 112-116. doi: 10.4236/nm.2013.42018.
 J. W. McDonald and C. Sadowsky, “Spinal-Cord Injury,” Lancet, Vol. 359, No. 9304, 2002, pp. 417-425.
 M. T. Filbin, “Axon Regeneration: Vaccinating against Spinal Cord Injury,” Current Biology, Vol. 10, No. 3, 2000, pp. R100-R103.
 S. Yoshii, M. Oka, M. Shima, M. Akagi and A. Taniguchi, “Bridging a Spinal Cord Defect Using Collagen Filament,” Spine, Vol. 28, 2003, pp. 2346-2351.
 L. G. Nygren, L. Olson and A. Seiger, “Mnoaminergic Reinnervation of the Transected Spinal Cord by Homologous Fetal Brain Grafts,” Brain Research, Vol. 129, No. 2, 1977, pp. 227-235.
 G. Galabov, “Regeneration of Sectioned Spinal Cord by Implanatation of a Peripheral Nerve,” Doklady Bolgarskoi Akademii Nauk, Vol. 19, 1966, pp. 449-452.
 J. Cde la Torre, “Catecholamine Fiber Regeneration across a Collagen Bioimplant after Spinal Cord Transection,” Brain Research Bulletin, Vol. 9, No. 1-6, 1982, pp. 545-552. doi:10.1016/0361-9230(82)90162-9
 M. Aoki, H. Kishima, K. Yoshimura, M. Ishihara, M. Ueno, K. Hata, et al., “Limited Functional Recovery in Rats with Complete Spinal Cord Injuryafter Transplantation of Whole-Layer Olfactory Mucosa: Laboratory Investigation,” Journal of Neurosurgery: Spine, Vol. 12, No. 2, 2010, pp. 122-130. doi:10.3171/2009.9.SPINE09233
 K. Iwatsuki, T. Yoshimine, H. Kishima, M. Aoki, K. Yoshimura, M. Ishihara, et al., “Transplantation of Olfactory Mucosa Following Spinal Cord Injury Promotes Recovery in Rats,” Neuroreport, Vol. 19, 2008, pp. 1249-1252. doi:10.1097/WNR.0b013e328305b70b
 J. Nakayama, T. Takao, H. Kiuchi, K. Yamamoto, S. Fukuhara, Y. Miyagawa, et al., “Olfactory Mucosal Transplantation after Spinal Cord Injury Improves Voiding Efficiency by Suppressing Detrusor-Sphincter Dyssynergia in Rats,” The Journal of Urology, Vol. 184, No. 2, 2010, pp. 775-782. doi:10.1016/j.juro.2010.03.105
 D. M. Basso, M. S. Beattie and J. C. Bresnahan, “A Sensitive and Reliable Locomotor Rating Scale for Open Field Testing in Rats,” Journal of Neurotrauma, Vol. 12, No. 1, 1995, pp. 1-21. doi:10.1089/neu.1995.12.1
 N. Keyvan-Fouladi, G. Raisman and Y. Li, “Functional Repair of the Corticospinal Tract by Delayed Transplantation of Olfactory Ensheathing Cells in Adult Rats,” The Journal of Neuroscience, Vol. 23, 2003, pp. 9428-9434.
 Y. Ogawa, K. Sawamoto, T. Miyata, S. Miyao, M. Watanabe, M. Nakamura, et al., “Transplantation of in Vitro—Expanded Fetal Neural Progenitor Cells Results in Neurogenesis and Functional Recovery after Spinal Cord Contusion Injury in Adult Rats,” Journal of Neuroscience Research, Vol. 69, No. 6, 2002, pp. 925-933.
 S. S. Han, D. Y. Kang, T. Mujtaba, M. S. Rao and I. Fischer, “Grafted Lineage-Restricted Precursors Differentiate Exclusively into Neurons in the Adult Spinal Cord,” Experimental Neurology, Vol. 177, No. 2, 2002, pp. 360-375. doi:10.1006/exnr.2002.7995
 J. W. McDonald, X. Z. Liu, Y. Qu, S. Liu, S. K. Mickey, D. Turetsky, et al., “Transplanted Embryonic Stem Cells Survive, Differentiate and Promote Recovery in Injured Rat Spinal Cord,” Nature Medicine, Vol. 5, 1999, pp. 1410-1412. doi:10.1038/70986
 Q. L. Cao, Y. P. Zhang, R. M. Howard, W. M. Walters, P. Tsoulfas, S. R. Whittemore, et al., “Pluripotent Stem Cells Engrafted into the Normal or Lesioned Adult Rat Spinal Cord Are Restricted to a Glial Lineage,” Experimental Neurology, Vol. 167, No. 1, 2001, pp. 48-58.
 S. Okada, K. Ishii, J. Yamane, A. Iwanami, T. Ikegami, H. Katoh, et al., “In Vivo Imaging of Engrafted Neural Stem Cells: Its Application in Evaluating the Optimal Timing of Transplantation for Spinal Cord Injury,” FASEB Journal, Vol. 19, 2005, pp. 1839-1841.
 D. L. Stocum, “Stem Cells in CNS and Cardiac Regeneration,” Advances in Biochemical Engineering, Vol. 93, 2005, pp. 135-159. doi:10.1007/b99969
 A. L. Calof, A. Bonnin, C. Crocker, S. Kawauchi, R. C. Murray, J. Shou, et al., “Progenitor Cells of the Olfactory Receptor Neuron Lineage,” Microscopy Research and Technique, Vol. 58, No. 3, 2002, pp. 176-188.
 A. M. Cunningham, P. B. Manis, R. R. Reed and G. V. Ronnett, “Olfactory Receptor Neurons Exist as Distinct Subclasses of Immature and Mature Cells in Primary Culture,” Neuroscience, Vol. 93, No. 4, 1999, pp. 1301-1312. doi:10.1016/S0306-4522(99)00193-1
 F. J. Roisen, K. M. Klueber, C. L. Lu, L. M. Hatcher, A. Dozier, C. B. Shields, et al., “Adult Human Olfactory Stem Cells,” Brain Research, Vol. 890, No. 1, 2001, pp. 11-22. doi:10.1016/S0006-8993(00)03016-X
 S. C. Barnett and J. S. Riddell, “Olfactory Ensheathing Cells (OECs) and Thetreatment of CNS Injury: Advantages and Possible Caveats,” Journal of Anatomy, Vol. 204, No. 1, 2004, pp. 57-67.
 Y. Li, P. M. Field and G. Raisman, “Repair of Adult Rat Corticospinal Tract by Transplants of Olfactory Ensheathing Cells,” Science, Vol. 277, No. 5334, 1997, pp. 2000-2002. doi:10.1126/science.277.5334.2000
 A. Ramon-Cueto and F. Valverde, “Olfactory Bulb Ensheathing Glia: A Unique Cell Type with Axonal Growth-Promoting Properties,” Glia, Vol. 14, No. 3, 1995, pp. 163-173. doi:10.1002/glia.440140302
 P. M. Smith, A. Lakatos, S. C. Barnett, N. D. Jeffery, R. J. Franklin, et al., “Cryopreserved Cells Isolated from the Adult Canine Olfactory Bulb Are Capable of Extensive Remyelination Following Transplantation into the Adult Rat CNS,” Experimental Neurology, Vol. 176, No. 2, 2002, pp. 402-406. doi:10.1006/exnr.2002.7936
 K. Kataoka, Y. Suzuki, M. Kitada, T. Hashimoto, H. Chou, H. Bai, et al., “Alginate Enhances Elongation of Early Regenerating Axons in Spinal Cord of Young Rats,” Tissue Engineering, Vol. 10, No. 3-4, 2004, pp. 493-504. doi:10.1089/107632704323061852
 M. J. Moore, J. A. Friedman, E. B. Lewellyn, S. M. Mantila, A. J. Krych, S. Ameenuddin, et al., “Multiple-Channel Scaffolds to Promote Spinal Cord Axon Regeneration,” Biomaterials, Vol. 27, No. 3, 2006, pp. 419-429. doi:10.1016/j.biomaterials.2005.07.045
 S. Stokols and M. H. Tuszynski, “Freeze-Dried Agarose Scaffolds with Uniaxial Channels Stimulate and Guide Linear Axonal Growth Following Spinal Cord Injury,” Biomaterials, Vol. 27, No. 3, 2006, pp. 443-451.
 F. Feron, C. Perry, J. J. McGrath and A. Mackay-Sim, “New Techniques for Biopsy and Culture of Human Olfactory Epithelial Neurons,” Archives of Otolaryngology—Head and Neck Surgery, Vol. 124, 1998, pp. 861-866.