Journal article
Transplants of cells genetically modified to express neurotrophin‐3 rescue axotomized Clarke's nucleus neurons after spinal cord hemisection in adult rats
Journal of neuroscience research, v 65(6), pp 549-564
15 Sep 2001
PMID: 11550223
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
To test the idea that genetically engineered cells can rescue axotomized neurons, we transplanted fibroblasts and immortalized neural stem cells (NSCs) modified to express neurotrophic factors into the injured spinal cord. The neurotrophin‐3 (NT‐3) or nerve growth factor (NGF) transgene was introduced into these cells using recombinant retroviral vectors containing an internal ribosome entry site (IRES) sequence and the β‐galactosidase or alkaline phosphatase reporter gene. Bioassay confirmed biological activity of the secreted neurotrophic factors. Clarke's nucleus (CN) axons, which project to the rostral spinal cord and cerebellum, were cut unilaterally in adult rats by T8 hemisection. Rats received transplants of fibroblasts or NSCs genetically modified to express NT‐3 or NGF and a reporter gene, only a reporter gene, or no transplant. Two months postoperatively, grafted cells survived at the hemisection site. Grafted fibroblasts and NSCs expressed a reporter gene and immunoreactivity for the NGF or NT‐3 transgene. Rats receiving no transplant or a transplant expressing only a reporter gene showed a 30% loss of CN neurons in the L1 segment on the lesioned side. NGF‐expressing transplants produced partial rescue compared with hemisection alone. There was no significant neuron loss in rats receiving grafts of either fibroblasts or NSCs engineered to express NT‐3. We postulate that NT‐3 mediates survival of CN neurons through interaction with trkC receptors, which are expressed on CN neurons. These results support the idea that NT‐3 contributes to long‐term survival of axotomized CN neurons and show that genetically modified cells rescue axotomized neurons as efficiently as fetal CNS transplants. J. Neurosci. Res. 65:549–564, 2001. © 2001 Wiley‐Liss, Inc.
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Details
- Title
- Transplants of cells genetically modified to express neurotrophin‐3 rescue axotomized Clarke's nucleus neurons after spinal cord hemisection in adult rats
- Creators
- B. Timothy HimesYi LiuJoanna M SolowskaEvan Y SnyderItzhak FischerAlan Tessler
- Publication Details
- Journal of neuroscience research, v 65(6), pp 549-564
- Publisher
- John Wiley & Sons, Inc; New York
- Number of pages
- 16
- Grant note
- Department of Veteran Affairs NIH (NS24707)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Neurobiology and Anatomy
- Web of Science ID
- WOS:000170899200010
- Scopus ID
- 2-s2.0-0035885111
- Other Identifier
- 991014878313004721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Neurosciences