PMID- 12904465
OWN - NLM
STAT- MEDLINE
DCOM- 20030909
LR  - 20200225
IS  - 1529-2401 (Electronic)
IS  - 0270-6474 (Print)
IS  - 0270-6474 (Linking)
VI  - 23
IP  - 18
DP  - 2003 Aug 6
TI  - 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.
PG  - 7045-58
AB  - The present study uniquely combines olfactory ensheathing glia (OEG) implantation 
      with ex vivo adenoviral (AdV) vector-based neurotrophin gene therapy in an 
      attempt to enhance regeneration after cervical spinal cord injury. Primary OEG 
      were transduced with AdV vectors encoding rat brain-derived neurotrophic factor 
      (BDNF), neurotrophin-3 (NT-3), or bacterial marker protein beta-galactosidase 
      (LacZ) and subsequently implanted into adult Fischer rats directly after 
      unilateral transection of the dorsolateral funiculus. Implanted animals received 
      a total of 2 x 105 OEG that were subjected to transduction with 
      neurotrophin-encoding AdV vector, AdV-LacZ, or no vector, respectively. At 4 
      months after injury, lesion volumes were smaller in all OEG implanted rats and 
      significantly reduced in size after implantation of neurotrophin-encoding AdV 
      vector-transduced OEG. All OEG grafts were filled with neurofilament-positive 
      axons, and AdV vector-mediated expression of BDNF by implanted cells 
      significantly enhanced regenerative sprouting of the rubrospinal tract. 
      Behavioral analysis revealed that OEG-implanted rats displayed better locomotion 
      during horizontal rope walking than unimplanted lesioned controls. Recovery of 
      hind limb function was also improved after implantation of OEG that were 
      transduced with a BDNF- or NT-3-encoding AdV vector. Hind limb performance during 
      horizontal rope locomotion did directly correlate with lesion size, suggesting 
      that neuroprotective effects of OEG implants contributed to the level of 
      functional recovery. Thus, our results demonstrate that genetic engineering of 
      OEG not only resulted in a cell that was more effective in promoting axonal 
      outgrowth but could also lead to enhanced recovery after injury, possibly by 
      sparing of spinal tissue.
FAU - Ruitenberg, Marc J
AU  - Ruitenberg MJ
AD  - Graduate School for Neurosciences Amsterdam, Netherlands Institute for Brain 
      Research, 1105 AZ, Amsterdam, The Netherlands.
FAU - Plant, Giles W
AU  - Plant GW
FAU - Hamers, Frank P T
AU  - Hamers FP
FAU - Wortel, Joke
AU  - Wortel J
FAU - Blits, Bas
AU  - Blits B
FAU - Dijkhuizen, Paul A
AU  - Dijkhuizen PA
FAU - Gispen, Willem Hendrik
AU  - Gispen WH
FAU - Boer, Gerard J
AU  - Boer GJ
FAU - Verhaagen, Joost
AU  - Verhaagen J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Neurosci
JT  - The Journal of neuroscience : the official journal of the Society for 
      Neuroscience
JID - 8102140
RN  - 0 (Nerve Growth Factors)
SB  - IM
MH  - Adenoviridae/*genetics
MH  - Animals
MH  - Cells, Cultured
MH  - Disease Models, Animal
MH  - Evoked Potentials, Motor/physiology
MH  - Female
MH  - Gene Expression
MH  - Gene Transfer Techniques
MH  - Genetic Vectors/*administration & dosage/genetics
MH  - Motor Activity
MH  - Neck
MH  - Nerve Growth Factors/*biosynthesis/genetics
MH  - Nerve Regeneration
MH  - Neuroglia/cytology/metabolism/*transplantation
MH  - Olfactory Bulb/cytology
MH  - Rats
MH  - Rats, Inbred F344
MH  - Recovery of Function
MH  - Red Nucleus/physiology
MH  - Spinal Cord/pathology
MH  - Spinal Cord Injuries/pathology/*therapy
MH  - Transgenes
MH  - Treatment Outcome
PMC - PMC6740651
EDAT- 2003/08/09 05:00
MHDA- 2003/09/10 05:00
PMCR- 2004/02/06
CRDT- 2003/08/09 05:00
PHST- 2003/08/09 05:00 [pubmed]
PHST- 2003/09/10 05:00 [medline]
PHST- 2003/08/09 05:00 [entrez]
PHST- 2004/02/06 00:00 [pmc-release]
AID - 23/18/7045 [pii]
AID - 10.1523/JNEUROSCI.23-18-07045.2003 [doi]
PST - ppublish
SO  - J Neurosci. 2003 Aug 6;23(18):7045-58. doi: 10.1523/JNEUROSCI.23-18-07045.2003.