NT-3 expression from engineered olfactory ensheathing glia promotes spinal sparing and regeneration

Ruitenberg, Marc J., Levison, Dane B., Lee, Seok Voon, Verhaagen, Joost, Harvey, Alan R. and Plant, Giles W. (2005) NT-3 expression from engineered olfactory ensheathing glia promotes spinal sparing and regeneration. Brain, 128 4: 839-853. doi:10.1093/brain/awh424

Author Ruitenberg, Marc J.
Levison, Dane B.
Lee, Seok Voon
Verhaagen, Joost
Harvey, Alan R.
Plant, Giles W.
Title NT-3 expression from engineered olfactory ensheathing glia promotes spinal sparing and regeneration
Journal name Brain   Check publisher's open access policy
ISSN 0006-8950
Publication date 2005-04-01
Sub-type Article (original research)
DOI 10.1093/brain/awh424
Volume 128
Issue 4
Start page 839
End page 853
Total pages 15
Place of publication London, U.K.
Publisher Oxford University Press
Language eng
Subject 1103 Clinical Sciences
Formatted abstract
Adenoviral (AdV) vectors encoding neurotrophin-3 (AdV-NT-3) or the bacterial marker enzyme ß-galactosidase (LacZ gene) were used to transduce olfactory ensheathing glia (OEG) cultures. AdV vector-transduced OEG expressed high levels of recombinant neurotrophin as shown by in situ hybridization and enzyme-linked immunosorbent assay techniques. The biological activity of vector-derived NT-3 was determined in a dorsal root ganglia neurite outgrowth assay. Engineered cell suspensions were then injected into adult Fischer 344 rat spinal cord immediately after unilateral cervical (C4) corticospinal tract (CST) transection. Transplanted animals received a total of 200 000 cells; either non-transduced OEG or OEG transduced with AdV vectors encoding NT-3 or LacZ, respectively. At 3 months after injury, lesion volumes were significantly smaller in all OEG-transplanted rats when compared with control (medium-injected) rats. Anterograde tracing of the lesioned CST projection, originating from the contralateral sensorimotor cortex, showed a significantly greater number of distal CST axons only in OEG-NT-3-transplanted rats. Behavioural analysis was performed on all rats using open field locomotion scoring, and a forelimb reaching task with Eshkol–Wachman movement notation. Analysis of behavioural tests revealed no significant differences in recovery between experimental groups, although movement analysis indicated that possible compensatory mechanisms were occurring after OEG implantation. The results demonstrate that OEG transplantation per se can promote tissue sparing after injury, but, after appropriate genetic modification, these olfactory-derived cells become far more effective in promoting long-distance maintenance/regeneration of lesioned adult CST axons. © The Author (2005). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved.
Keyword Corticospinal tract
Gene therapy
Olfactory ensheathing glia
Q-Index Code C1

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
School of Biomedical Sciences Publications
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Created: Thu, 21 Jan 2010, 02:06:43 EST by Gerald Martin on behalf of Faculty of Science