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	Transplantation of olfactory mucosa as a scaffold for axonal regeneration
following spinal cord contusion in rats

Koichi Iwatsuki M.D., Ph.D.1, Toshiki Yoshimine M.D., Ph.D. 1, Yoshiyuki
Sankai Ph.D.2, Masao Umegaki M.D., Ph.D. 1, Yu-ichiro Ohnishi M.D. 1,
Masahiro Ishihara M.D. 1, Takashi Moriwaki M.D. 1, Noriko Oda Ph.D. 1
1Department of Neurosurgery, Osaka University Medical School
2Faculty of Engineering� Information and Systems, University of Tsukuba
Address and correspondence to: Koichi Iwatsuki, MD, PhD
Department of Neurosurgery, Osaka University Medical School,
2-2 Yamadaoka, Suita, Osaka 565-0871, Japan
Tel.: +81-6-6879-3652
Fax: +81-6-6879-3659
E-mail address: kiwatsuki@nsurg.med.osaka-u.ac.jp
Key words: olfactory mucosa, spinal cord injury, transplantation, scaffold
Short title: Transplantation of olfactory mucosa
Abstract
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.
Introduction
 Traumatic spinal cord injury (SCI) is relatively common, and can result in
severe damage leading to partial or complete loss of motor and sensory
function caudal to the level of injury. This occurs as a result of severing of
descending and ascending fiber tracts. One of the most devastating
permanent complications following SCI is paraplegia, management of which
has been a constant challenge in clinical medicine. Facilitating restoration of
tract structure, and with it recovery of function, after SCI is of great interest
to neuroscientists. 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. After an SCI, astroglial scarring
occurs within lesioned areas 18. It has been shown that axonal regeneration
is in fact initiated in the injured spinal cord but that it is blocked by glial
scar formation 10. It seems that for successful axonal regeneration to take
place, a supportive local environment is required from an early stage after
the injury.
 Recently 29, a team reported partial success in bridging the ends of
the spinal cord after a complete resection using grafts of smooth muscle,
peripheral nerve 11, fetal brain cells 21, semi-fluid collagen material 8, and
embryonic spinal cord segments in the neonatal rat. These experiments
suggest that regeneration of spinal nerve fibers across a spinal cord defect
could be possible, under favorable conditions. To date, there have been very
few studies regarding events that occur in the early stages of autografts
transplantation.
 We have previously reported that grafts of the olfactory mucosa are0 ffective in restoring functional recovery in rats following spinal cord
transaction, with histological evidence of neuronal regeneration 1,13,20. In the
present 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.
Materials and Methods
Spinal cord injury model
Male Sprague-Dawley rats, weighing 250�300 g, were anesthetized using a
pentobarbiturate sodium/atropine mixture (5/5 mg/kg, intraperitoneally).
Rectal temperature was maintained at 37 � 0.5 �C using a heating pad. A
laminectomy was performed at the thoracic (Th) 8�9 vertebrae using a
microsurgery bone rongeur to expose the spinal cord without touching it. The
spinal cord, covered by the dura mater, was crush-injured by dropping a 10-g
metal rod from a height of 7.5 cm using a New York University (NYU)
impactor. Although crush injury is commonly simulated by dropping a
weight from a height of 2.5�5.0 cm 4, mild or moderate injuries tend to
produce high rates of spontaneous locomotor recovery in controls. We
dropped a rod from a height of 7.5 cm to cause severe crush injuries.
Dissection and preparation of olfactory and respiratory mucosa
Rats were deeply anesthetized using sodium pentobarbital (100 mg/kg) and
sacrificed by decapitation. The nasal septum was freed by removing the
lower jaw, upper teeth, and nasal turbinates. Both olfactory and respiratory
mucasae were identified on the septum. The olfactory mucosa is located in
the dorsocaudal portion and is easily identifiable by the yellowish
appearance of its surface. The respiratory mucosa is located ventrorostral to
the olfactory mucosa and identified by the grayish color of its surface. Each
mucosa was carefully dissected to exclude the border region between the
mucosae in order to avoid cross-contamination between the 2 types.
Transplantation of olfactory and respiratory mucosa
 A couple of weeks after injury, the injury site was exposed, and the
posterior sulcuses of the spinal cord were opened. Both olfactory and
respiratory mucosae were divided into approximately 0.5�1.0-mm sections.
Next, 2�3 sections of the olfactory and respiratory mucosae were gently
inserted into the sulcuses respectively. The each number of olfactory and
mucosa transplanted rats were five. The wound was sealed by suturing the
muscle and the skin overlying the exposed spine.
Behavioral assessment
 The Basso, Beattie, and Bresnahan (BBB) score is an operationally
defined 21-point scale. It is designed to assess the degree of hind limb
locomotor recovery following impact injury to the thoracic spinal cord in rats3. In the present study, the BBB score in each animal was determined by 2
independent observers, who were blinded to the purpose and other protocols
of this study. The scores were averaged and compared between the 2 groups
using the Student�s t test (unpaired). Statistical significance was set at p <
0.05.
Preparation of tissue for histology and immunohistochemistry
 For immunohistochemical examination, 3 rats from each of the
transplantation groups were sacrificed 8 weeks after the transplantation.
Rats were deeply anesthetized by an intraperitoneal injection of sodium
pentobarbital (100 mg/kg), and perfused intracardially with 50 ml PBS,
followed by 200 ml of a fixative containing 2% paraformaldehyde in 0.1 M
phosphate buffer, pH 7.4. Specimens were processed using a standard
procedure for embedding in OCT compound, and cut horizontally into
7-�m-thick frozen sections with a cryostat (CM1510S; Leica). Frozen sections were mounted on coated glass slides.
 For histological examination, horizontal sections were stained with
hematoxylin and eosin (HE), and used for observing blood vessels, and
measuring the volume of cavities in the spinal cord. For immunohistochemistry, sections were washed 3 times with PBS, and blocked
with a 0.1% bovine serum albumin solution containing 0.1% Tween 20 in
PBS for 30 min. Sections were then incubated overnight in a solution
containing primary antibodies as follows: anti-p75NGFR (Chemicon, Cat. No.MAB365; 1:500 in 0.1 M PBS pH 7.4) for olfactory ensheathing cells,
anti-glial fibrillary acidic protein (GFAP) monoclonal antibody (1:300;
Sigma) for astrocytes, and anti-neurofilament 200 kD rabbit polyclonal
antibody (1:100; Chemicon) for axons. After washing, the sections were
incubated overnight with secondary antibodies as follows: FITC- or
Cy-3-labeled anti-mouse IgG antibody (1:1000; Amersham Biosciences) for
astrocytes, or Cy-3-labeled anti-rabbit IgG antibody (1:1000; Amersham
Biosciences) for axons. Sections were then mounted and examined by a
fluorescence microscope (Axio Imager MI; Carl Zeiss).
 All experimental procedures were approved by the Animal Ethics
Committees of the Osaka University Medical School.
Results
The averaged BBB scores of the olfactory mucosa transplanted rats
(n = 5) were 3.13 � 1.12, 5.25 � 1.21, 6.88 � 1.34, and 10.83 � 1.23, measured
1, 2, 4, and 8 weeks after transplantation, respectively. The averaged BBB
scores of the respiratory mucosa transplanted rats (n = 5), measured over the
same time frame, were 2.2 � 0.84, 2.8 � 1.15, 3.5 � 1.02, and 4.0 � 0.71. These
data indicate that the recovery of hind limb movement in the olfactory
mucosa transplanted rats improved significantly in comparison to the
control, respiratory mucosa transplanted rats (p < 0.05)(Fig. 1). In the
histological assessment, expression of neurofilament was observed strongly
at the injury site in the olfactory mucosa transplanted rats(Fig.2,3). The numerous fibers that were strongly stained with neurofilament were surrounding the GFP-positive cells and penetrating the transplanted olfactory mucosa(Fig.3). In contrast, there were no apparent neurofilament stained fibers at the marginal spinal cord of the respiratory mucosa transplanted rats(Fig.4).
Discussion
 Injuries to the central nervous system (CNS) in humans are usually
associated with a low degree of neurological recovery and, in the majority of
cases, life-long debilitation. This lack of recovery, however, is not due to any
intrinsic inability of CNS axons to regenerate; rather, the environment of the
CNS is strongly inhibitory to axonal regeneration. Following SCI, astroglial
scars form within lesioned areas of the spinal cord 18. Although the majority
of known inhibitors of neurite outgrowth are myelin membrane proteins,
equally potent inhibitors have also been identified in astroglial scars, for
example, chondroitin sulfate proteoglycans and semaphoring 3A.
Manipulating the local environment in order to provide a favorable scaffold,
supportive of axonal regeneration, is one of the more promising strategies for
treatment of SCI.
 Spinal cord reconstruction using implantation of cells from various sources
has been gaining attention in recent years 15,22. Neuronal stem cells have the
potential to differentiate into both neuronal and glial cells, and are therefore
prime candidates for cell replacement therapy following CNS injury.
Neuronal stem cells constitutively secrete significant quantities of several
neurotrophic factors that act to support host axonal regeneration after SCI12.
Partial restoration of function after contusion of the spinal cord has been
accomplished by injecting neural/glial precursors (NSCs), differentiated in
vitro from mouse embryonic stem cells, into the lesion 9 days after injury 17.
However, implantation of NSCs alone did not produce any significant
restorative effect because the majority of the NSCs grafted into the spinal
cord differentiated with an astrocytic phenotype 6,12. Although astrocytes can
secrete neurotrophic factors and limit the extent of the inflammatory
reaction, extensive astroglial scarring within the lesioned area blocks axon
growth.
 However, one of the major disadvantages associated with implantation or
injection of cells alone is the limited proportion of viable cells surviving in
the injury site after the procedure, as cells tend to migrate away from the
injury site 23. To achieve significant functional reconstruction of the spinal
cord after spinal cord injuries, it is either necessary to populate lesion sites
with tissue-specific, regeneration-competent cells that replace or rescue
dying cells, or to activate endogenous neural progenitor cells that do likewise27.
 In this study, numerous neurofilaments were observed strongly in the
transplanted olfactory mucosa. Unlike respiratory mucosa, it permits axonal
regeneration after SCI and therefore may be an appropriate scaffold on
which to reconstruct axons.
 Indeed, the olfactory mucosa is an excellent autologous source of
adult neuronal precursor cells. The neurons and the sustentacular cells
there renew themselves constantly throughout life by proliferation of basal
global stem cells 5,7,25. Furthermore, the mucosa contains olfactory
ensheathing cells, which have previously been the subject of much attention
for their potential in the repair of spinal cord injuries 2,26,16,24. Recent studies
of spinal cord axon regeneration have reported good long-term results using
various types of tissue scaffolds 14,19,28. Olfactory tissue would allow
autologous transplantation, is easily accessible, and can be obtained by a
simple biopsy that is performed through the external nares 9. These
considerations, combined with the results of the present study, make nasal
mucosa an attractive potential scaffold for axonal regeneration.
Conclusions
 As we have previously reported, olfactory mucosa transplantation following
spinal cord injury can support at least partial hind limb motor recovery. In
this study, we identified numerous axons surrounding the transplanted cells,
and penetrating the mucosa at the transplant site without marginal spinal
white matter. Olfactory mucosa might therefore be a more suitable scaffold
for axonal regeneration than white matter, which contains inhibiting factors
for axonal regeneration in the spinal cord.

0This study was supported by the "Center for Cybernics Research-World
Leading Human-Assistive Technology Supporting a Long-Lived and Healthy
Society'" granted through the �Funding Program for World-Leading
Innovative R&D on Science and Technology (FIRST Program),� initiated by
the Council for Science and Technology Policy.
Figure Legends
Fig.1  A significantly greater degree of functional recovery as measured by
hindlimb usage was observed in the olfactory mucosa transplanted rats (OM)
compared with the respiratory mucosa transplanted rats (RM) 4 weeks after
the transplantation (; ). BBB: Basso, Beattie, and Bresnahan Locomotor
Rating Scale.
Fig.2  Histology (HE). A transplanted mucosa (indicated by an arrow) is
recognizable in the contused spinal cord.
Fig.3  Immunohistological study. Numerous fibers (arrow), strongly stained
with neurofilament, are seen penetrating the transplanted olfactory mucosa
(a). The fibers surround the GFP-positive cells (b).
Fig.4  Immunohistological study. No apparent fibers stained with
neurofilament are found in the respiratory mucosa (GFP positive)
transplanted spinal cord.


References
1. Aoki M, Kishima H, Yoshimura K, Ishihara M, Ueno, M, Hata K, et al.
Limited functional recovery in rats with complete spinal cord injury
after transplantation of whole-layer olfactory mucosa: laboratory
investigation. J Neurosurg Spine. 2010;12:122-130
2. Barnett SC, Riddell JS. Olfactory ensheathing cells (OECs) and the
treatment of CNS injury: advantages and possible caveats. J Anat.
2004;204:57-67
3. Basso DM, Beattie MS, Bresnahan JC. A sensitive and reliable
locomotor rating scale for open field testing in rats. J Neurotrauma.
1995;12:1-21
4. Basso DM, Beattie MS, Bresnahan JC. Graded histological and
locomotor outcomes after spinal cord contusion using the NYU
weight-drop device versus transection. Exp Neurol. 1996;139:244-256
5. Calof AL, Bonnin A, Crocker C, Kawauchi S, Murray RC, Shou J, et al.
Progenitor cells of the olfactory receptor neuron lineage. Microsc Res
Tech. 2002;58:176-188
6. Cao QL, Zhang YP, Howard RM, Walters WM, Tsoulfas P, Whittemore
SR, et al. Pluripotent stem cells engrafted into the normal or lesioned
adult rat spinal cord are restricted to a glial lineage. Exp Neurol.
2001; 67:48-58
7. Cunningham AM, Manis PB, Reed RR, Ronnett GV. Olfactory
receptor neurons exist as distinct subclasses of immature and mature
cells in primary culture. Neuroscience. 1999;93:1301-1312
8. de la Torre JC. Catecholamine fiber regeneration across a collagen
bioimplant after spinal cord transection. Brain Res Bull.
1982;9:545-552
9. Feron F, Perry C, McGrath JJ, Mackay-Sim A. New techniques for
biopsy and culture of human olfactory epithelial neurons. Arch
Otolaryngol Head Neck Surg. 1998;124:861-866
10. Filbin MT. Axon regeneration: Vaccinating against spinal cord injury.
Curr Biol. 2000;10:R100-103
11. Galabov G. Regeneration of sectioned spinal cord by implanatation of
a peripheral nerve. Dokl Bulg Acad Nauk. 1966;19:449-452
12. Han SS, Kang DY, Mujtaba T, Rao, MS, Fischer, I. Grafted
lineage-restricted precursors differentiate exclusively into neurons in
the adult spinal cord. Exp Neurol. 2002;177:360-375
13. Iwatsuki K, Yoshimine T, Kishima H, Aoki M, Yoshimura K, Ishihara
M, et al. Transplantation of olfactory mucosa following spinal cord
injury promotes recovery in rats. Neuroreport. 2008;19:1249-1252
14. Kataoka K, Suzuki Y, Kitada M, Hashimoto T, Chou H, Bai H, et al.
Alginate enhances elongation of early regenerating axons in spinal
cord of young rats. Tissue Eng. 2004;10:493-504
15. Keyvan-Fouladi N, Raisman G, Li Y. Functional repair of the
corticospinal tract by delayed transplantation of olfactory ensheathing
cells in adult rats. J Neurosci. 2003;23:9428-9434
16. Li Y, Field PM, Raisman G. Repair of adult rat corticospinal tract by
transplants of olfactory ensheathing cells. Science.
1997;277:2000-2002
17. McDonald JW, Liu XZ, Qu Y, Liu S, Mickey SK, Turetsky D, et al.
Transplanted embryonic stem cells survive, differentiate and promote
recovery in injured rat spinal cord. Nat Med. 1999;5:1410-1412
18. McDonald JW, Sadowsky C. Spinal-cord injury. Lancet.
2002;359:417-425
19. Moore MJ, Friedman JA, Lewellyn EB, Mantila SM, Krych AJ,
Ameenuddin S, et al. Multiple-channel scaffolds to promote spinal
cord axon regeneration. Biomaterials. 2006, 27:419-429
20. Nakayama J, Takao T, Kiuchi H, Yamamoto K, Fukuhara S,
Miyagawa Y, et al. Olfactory mucosal transplantation after spinal
cord injury improves voiding efficiency by suppressing
detrusor-sphincter dyssynergia in rats. J Urol. 2010;184:775-782
21. Nygren LG, Olson L, Seiger A Mnoaminergic reinnervation of the
transected spinal cord by homologous fetal brain grafts. Brain Res.
1977;129:227-235
22. Ogawa Y, Sawamoto K, Miyata T, Miyao S, Watanabe M, Nakamura
M, 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. J Neurosci Res. 2002;69:925-933
23. Okada S, Ishii K, Yamane J, Iwanami A, Ikegami T, Katoh H, et al. In
vivo imaging of engrafted neural stem cells: its application in
evaluating the optimal timing of transplantation for spinal cord injury.
Faseb J. 2005;19:1839-1841
24. Ramon-Cueto A, Valverde F. Olfactory bulb ensheathing glia: a
unique cell type with axonal growth-promoting properties. Glia.
1995;14:163-173
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al. Adult human olfactory stem cells. Brain Res. 2001;890:11-22
26. Smith PM, Lakatos A, Barnett SC, Jeffery ND, Franklin RJ, et al.
Cryopreserved cells isolated from the adult canine olfactory bulb are
capable of extensive remyelination following transplantation into the
adult rat CNS. Exp Neurol. 2002;176:402-406
27. Stocum DL. Stem cells in CNS and cardiac regeneration. Adv Biochem
Eng Biotechnol. 2005;93:135-159
28. Stokols S, Tuszynski MH. Freeze-dried agarose scaffolds with uniaxial
channels stimulate and guide linear axonal growth following spinal
cord injury. Biomaterials. 2006;27:443-451
29. Yoshii S, Oka M, Shima M, Akagi M, Taniguchi A. Bridging a spinal
cord defect using collagen filament. Spine (Phila Pa 1976).
2003;28:2346-2351


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