 |
Previous Article | Next Article 
The Journal of Neuroscience, December 15, 1998, 18(24):10514-10524
Regeneration of Adult Rat Corticospinal Axons Induced by
Transplanted Olfactory Ensheathing Cells
Ying
Li,
Pauline M.
Field, and
Geoffrey
Raisman
The Norman and Sadie Lee Research Centre, Division of Neurobiology,
National Institute for Medical Research, Medical Research
Council, London NW7 1AA, United Kingdom
Precisely localized focal stereotaxic electrolytic lesions were
made in the corticospinal tract at the level of the first to second
cervical segments in the adult rat. This consistently destroyed all
central nervous tissue elements (axons, astrocytes, oligodendrocytes,
microglia, and microvessels) in a highly circumscribed area.
In a group of these rats immediately after lesioning, a
suspension of cultured adult olfactory ensheathing cells was
transplanted into the lesion site. Within the first week after
transplantation, the cut corticospinal axons (identified by anterograde
transport of biotin dextran) extended caudally along the axis of the
corticospinal tract as single, fine, minimally branched sprouts that
ended in a simple tip, often preceded by a small varicosity. By 3 weeks, the regenerating axons, ensheathed by P0-positive
peripheral myelin had accumulated into parallel bundles, which now
extended across the full length of the lesioned area and reentered the
caudal part of the host corticospinal tract.
The transplants contained two main types of cells: (1)
p75-expressing S cells, which later formed typical peripheral
one-to-one myelin sheaths around individual ensheathed axons, and (2)
fibronectin-expressing A cells, which aggregated into tubular sheaths
enclosing bundles of myelinated axons. The point of reentry of the
axons into the central nervous territory of the caudal host
corticospinal tract was marked by the resumption of oligodendrocytic
myelination. Thus the effect of the transplant was to form a
"patch" of peripheral-type tissue across which the cut central
axons regenerated and then continued to grow along their original
central pathway.
Key words:
regeneration; olfactory ensheathing cells; corticospinal tract; white matter; adult spinal cord repair; axon
growth; myelinated tracts; transplantation
Copyright © 1998 Society for Neuroscience 0270-6474/98/182410514-11$05.00/0
This article has been cited by other articles:

|
 |

|
 |
 
A. Hurtado, H. Podinin, M. Oudega, and B. Grimpe
Deoxyribozyme-mediated knockdown of xylosyltransferase-1 mRNA promotes axon growth in the adult rat spinal cord
Brain,
October 1, 2008;
131(10):
2596 - 2605.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
P. Verma, G. Garcia-Alias, and J. W. Fawcett
Spinal Cord Repair: Bridging the Divide
Neurorehabil Neural Repair,
September 1, 2008;
22(5):
429 - 437.
[Abstract]
[PDF]
|
 |
|

|
 |

|
 |
 
Z. Su, L. Cao, Y. Zhu, X. Liu, Z. Huang, A. Huang, and C. He
Nogo enhances the adhesion of olfactory ensheathing cells and inhibits their migration
J. Cell Sci.,
June 1, 2007;
120(11):
1877 - 1887.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. Toft, D. T. Scott, S. C. Barnett, and J. S. Riddell
Electrophysiological evidence that olfactory cell transplants improve function after spinal cord injury
Brain,
April 1, 2007;
130(4):
970 - 984.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. M. Smith, P. Lunga, D. Story, N. Harris, J. Le Belle, M. F James, J. D. Pickard, and J. W. Fawcett
Inosine promotes recovery of skilled motor function in a model of focal brain injury
Brain,
April 1, 2007;
130(4):
915 - 925.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
P. Lu, H. Yang, M. Culbertson, L. Graham, A. J. Roskams, and M. H. Tuszynski
Olfactory Ensheathing Cells Do Not Exhibit Unique Migratory or Axonal Growth-Promoting Properties after Spinal Cord Injury
J. Neurosci.,
October 25, 2006;
26(43):
11120 - 11130.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. D. Houle, V. J. Tom, D. Mayes, G. Wagoner, N. Phillips, and J. Silver
Combining an autologous peripheral nervous system "bridge" and matrix modification by chondroitinase allows robust, functional regeneration beyond a hemisection lesion of the adult rat spinal cord.
J. Neurosci.,
July 12, 2006;
26(28):
7405 - 7415.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. Sasaki, J. A. Black, K. L. Lankford, H. A. Tokuno, S. G. Waxman, and J. D. Kocsis
Molecular Reconstruction of Nodes of Ranvier after Remyelination by Transplanted Olfactory Ensheathing Cells in the Demyelinated Spinal Cord
J. Neurosci.,
February 8, 2006;
26(6):
1803 - 1812.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
F. Feron, C. Perry, J. Cochrane, P. Licina, A. Nowitzke, S. Urquhart, T. Geraghty, and A. Mackay-Sim
Autologous olfactory ensheathing cell transplantation in human spinal cord injury
Brain,
December 1, 2005;
128(12):
2951 - 2960.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
S. Johansson, I-H. Lee, L. Olson, and C. Spenger
Olfactory ensheathing glial co-grafts improve functional recovery in rats with 6-OHDA lesions
Brain,
December 1, 2005;
128(12):
2961 - 2976.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. W. Richter, P. A. Fletcher, J. Liu, W. Tetzlaff, and A. J. Roskams
Lamina Propria and Olfactory Bulb Ensheathing Cells Exhibit Differential Integration and Migration and Promote Differential Axon Sprouting in the Lesioned Spinal Cord
J. Neurosci.,
November 16, 2005;
25(46):
10700 - 10711.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. G. Boyd, R. Doucette, and M. D. Kawaja
Defining the role of olfactory ensheathing cells in facilitating axon remyelination following damage to the spinal cord
FASEB J,
May 1, 2005;
19(7):
694 - 703.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. J. Ruitenberg, D. B. Levison, S. V. Lee, J. Verhaagen, A. R. Harvey, and G. W. Plant
NT-3 expression from engineered olfactory ensheathing glia promotes spinal sparing and regeneration
Brain,
April 1, 2005;
128(4):
839 - 853.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. Sasaki, K. L. Lankford, M. Zemedkun, and J. D. Kocsis
Identified Olfactory Ensheathing Cells Transplanted into the Transected Dorsal Funiculus Bridge the Lesion and Form Myelin
J. Neurosci.,
September 29, 2004;
24(39):
8485 - 8493.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
B. D. Burrell and C. L. Sahley
Multiple Forms of Long-Term Potentiation and Long-Term Depression Converge on a Single Interneuron in the Leech CNS
J. Neurosci.,
April 21, 2004;
24(16):
4011 - 4019.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
L. Cao, L. Liu, Z.-Y. Chen, L.-M. Wang, J.-L. Ye, H.-Y. Qiu, C.-L. Lu, and C. He
Olfactory ensheathing cells genetically modified to secrete GDNF to promote spinal cord repair
Brain,
March 1, 2004;
127(3):
535 - 549.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. G. Boyd, J. Lee, V. Skihar, R. Doucette, and M. D. Kawaja
LacZ-expressing olfactory ensheathing cells do not associate with myelinated axons after implantation into the compressed spinal cord
PNAS,
February 17, 2004;
101(7):
2162 - 2166.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
N. Keyvan-Fouladi, G. Raisman, and Y. Li
Functional Repair of the Corticospinal Tract by Delayed Transplantation of Olfactory Ensheathing Cells in Adult Rats
J. Neurosci.,
October 15, 2003;
23(28):
9428 - 9434.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
Y. Li, Y. Sauve, D. Li, R. D. Lund, and G. Raisman
Transplanted Olfactory Ensheathing Cells Promote Regeneration of Cut Adult Rat Optic Nerve Axons
J. Neurosci.,
August 27, 2003;
23(21):
7783 - 7788.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. J. Ruitenberg, G. W. Plant, F. P. T. Hamers, J. Wortel, B. Blits, P. A. Dijkhuizen, W. H. Gispen, G. J. Boer, and J. Verhaagen
Ex Vivo Adenoviral Vector-Mediated Neurotrophin Gene Transfer to Olfactory Ensheathing Glia: Effects on Rubrospinal Tract Regeneration, Lesion Size, and Functional Recovery after Implantation in the Injured Rat Spinal Cord
J. Neurosci.,
August 6, 2003;
23(18):
7045 - 7058.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
G. Raisman
A promising therapeutic approach to spinal cord repair
J R Soc Med,
June 1, 2003;
96(6):
259 - 261.
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. Lakatos, P. M. Smith, S. C. Barnett, and R. J. M. Franklin
Meningeal cells enhance limited CNS remyelination by transplanted olfactory ensheathing cells
Brain,
March 1, 2003;
126(3):
598 - 609.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
Y. Li, P. Decherchi, and G. Raisman
Transplantation of Olfactory Ensheathing Cells into Spinal Cord Lesions Restores Breathing and Climbing
J. Neurosci.,
February 1, 2003;
23(3):
727 - 731.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
H. H. Nash, R. C. Borke, and J. J. Anders
Ensheathing Cells and Methylprednisolone Promote Axonal Regeneration and Functional Recovery in the Lesioned Adult Rat Spinal Cord
J. Neurosci.,
August 15, 2002;
22(16):
7111 - 7120.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
O. Guntinas-Lichius, K. Wewetzer, T. L. Tomov, N. Azzolin, S. Kazemi, M. Streppel, W. F. Neiss, and D. N. Angelov
Transplantation of Olfactory Mucosa Minimizes Axonal Branching and Promotes the Recovery of Vibrissae Motor Performance after Facial Nerve Repair in Rats
J. Neurosci.,
August 15, 2002;
22(16):
7121 - 7131.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
T. Takami, M. Oudega, M. L. Bates, P. M. Wood, N. Kleitman, and M. B. Bunge
Schwann Cell But Not Olfactory Ensheathing Glia Transplants Improve Hindlimb Locomotor Performance in the Moderately Contused Adult Rat Thoracic Spinal Cord
J. Neurosci.,
August 1, 2002;
22(15):
6670 - 6681.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
G. W. Plant, P. F. Currier, E. P. Cuervo, M. L. Bates, Y. Pressman, M. B. Bunge, and P. M. Wood
Purified Adult Ensheathing Glia Fail to Myelinate Axons under Culture Conditions that Enable Schwann Cells to Form Myelin
J. Neurosci.,
July 15, 2002;
22(14):
6083 - 6091.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. Lu, F. Feron, A. Mackay-Sim, and P. M. E. Waite
Olfactory ensheathing cells promote locomotor recovery after delayed transplantation into transected spinal cord
Brain,
January 1, 2002;
125(1):
14 - 21.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. V. Coumans, T. T.-S. Lin, H. N. Dai, L. MacArthur, M. McAtee, C. Nash, and B. S. Bregman
Axonal Regeneration and Functional Recovery after Complete Spinal Cord Transection in Rats by Delayed Treatment with Transplants and Neurotrophins
J. Neurosci.,
December 1, 2001;
21(23):
9334 - 9344.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. B. Bunge
Book Review: Bridging Areas of Injury in the Spinal Cord
Neuroscientist,
August 1, 2001;
7(4):
325 - 339.
[Abstract]
[PDF]
|
 |
|

|
 |

|
 |
 
M. Murray and I. Fischer
Transplantation and Gene Therapy: Combined Approaches for Repair of Spinal Cord Injury
Neuroscientist,
February 1, 2001;
7(1):
28 - 41.
[Abstract]
[PDF]
|
 |
|

|
 |

|
 |
 
H. B. Treloar, J. C. Bartolomei, B. W. Lipscomb, and C. A. Greer
Mechanisms of Axonal Plasticity: Lessons from the Olfactory Pathway
Neuroscientist,
February 1, 2001;
7(1):
55 - 63.
[Abstract]
[PDF]
|
 |
|

|
 |

|
 |
 
T W Ford, C W Vaughan, and P A Kirkwood
Changes in the distribution of synaptic potentials from bulbospinal neurones following axotomy in cat thoracic spinal cord
J. Physiol.,
April 1, 2000;
524(1):
163 - 178.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
K. T. Tisay and B. Key
The Extracellular Matrix Modulates Olfactory Neurite Outgrowth on Ensheathing Cells
J. Neurosci.,
November 15, 1999;
19(22):
9890 - 9899.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
L. I. Benowitz, D. E. Goldberg, J. R. Madsen, D. Soni, and N. Irwin
Inosine stimulates extensive axon collateral growth in the rat corticospinal tract after injury
PNAS,
November 9, 1999;
96(23):
13486 - 13490.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
Y. Liu, D. Kim, B. T. Himes, S. Y. Chow, T. Schallert, M. Murray, A. Tessler, and I. Fischer
Transplants of Fibroblasts Genetically Modified to Express BDNF Promote Regeneration of Adult Rat Rubrospinal Axons and Recovery of Forelimb Function
J. Neurosci.,
June 1, 1999;
19(11):
4370 - 4387.
[Abstract]
[Full Text]
[PDF]
|
 |
|
|

|