Viral vector-mediated gene transfer of neurotrophins to promote regeneration of the injured spinal cord

Hendriks, William T.J., Ruitenberg, Marc J., Blits, Bas, Boer, Gerard J. and Verhaagen, Joost (2004). Viral vector-mediated gene transfer of neurotrophins to promote regeneration of the injured spinal cord. In Aloe, Luigi and Calzà, Laura (Ed.), NGF and related molecules in health and disease (pp. 451-476) Amsterdam , Netherlands: Elesevier. doi:10.1016/S0079-6123(03)46029-9


Author Hendriks, William T.J.
Ruitenberg, Marc J.
Blits, Bas
Boer, Gerard J.
Verhaagen, Joost
Title of chapter Viral vector-mediated gene transfer of neurotrophins to promote regeneration of the injured spinal cord
Title of book NGF and related molecules in health and disease
Place of Publication Amsterdam , Netherlands
Publisher Elesevier
Publication Year 2004
Sub-type Other
DOI 10.1016/S0079-6123(03)46029-9
Series Progress in brain research , v. 146
ISBN 978-0-444-51472-1
ISSN 0079-6123
Editor Aloe, Luigi
Calzà, Laura
Volume number 146
Chapter number 29
Start page 451
End page 476
Total pages 26
Total chapters 33
Language eng
Subjects 1109 Neurosciences
Abstract/Summary Injuries to the adult mammalian spinal cord often lead to severe damage to both ascending (sensory) pathways and descending (motor) nerve pathways without the perspective of complete functional recovery. Future spinal cord repair strategies should comprise a multi-factorial approach addressing several issues, including optimalization of survival and function of spared central nervous system neurons in partial lesions and the modulation of trophic and inhibitory influences to promote and guide axonal regrowth. Neurotrophins have emerged as promising molecules to augment neuroprotection and neuronal regeneration. Although intracerebroventricular, intrathecal and local protein delivery of neurotrophins to the injured spinal cord has resulted in enhanced survival and regeneration of injured neurons, there are a number of drawbacks to these methods. Viral vector-mediated transfer of neurotrophin genes to the injured spinal cord is emerging as a novel and effective strategy to express neurotrophins in the injured nervous system. Ex vivo transfer of neurotrophic factor genes is explored as a way to bridge lesions cavities for axonal regeneration. Several viral vector systems, based on herpes simplex virus, adenovirus, adeno-associated virus, lentivirus, and moloney leukaemia virus, have been employed. The genetic modification of fibroblasts, Schwann cells, olfactory ensheathing glia cells, and stem cells, prior to implantation to the injured spinal cord has resulted in improved cellular nerve guides. So far, neurotrophic factor gene transfer to the injured spinal cord has led to results comparable to those obtained with direct protein delivery, but has a number of advantages. The steady advances that have been made in combining new viral vector systems with a range of promising cellular platforms for ex vivo gene transfer (e.g., primary embryonic neurons, Schwann cells, olfactory ensheating glia cells and neural stem cells) holds promising perspectives for the development of new neurotrophic factor-based therapies to repair the injured nervous system.
Keyword Central nervous system
Gene therapy
Neurotrophins
Regeneration
Spinal cord injury
Viral vectors
Q-Index Code BX
Additional Notes ISSN: 0079-6123

 
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Created: Wed, 27 Jan 2010, 23:53:58 EST by Kelly Whitehorne on behalf of Faculty of Science