A new approach to create a growth-permissive environment for axonal regeneration after spinal cord injury (SCI) lies in the use of olfactory ensheathing cells (OECs) as transplant material. OECs normally provide a permissive environment for olfactory axons to regenerate in the adult CNS and OEC transplantation into a rodent SCI significantly enhances functional recovery through a mechanism of axonal guidance. We found that these cells produce neurotrophic factors (NTFs) in vitro. Since NTFs promote axonal growth and target connection in the CNS, the mechanism by which OECs enhance functional recovery after SCI could involve NTFs in addition to axonal guidance factors. The goal is to elucidate the mechanism by which OECs enhance functional recovery after SCI through the following Specific Aims: 1) OECs produce NTF mRNAs in the injured hamster spinal cord in vivo. In situ hybridization will measure NTF in OECs in vivo. 2) OECs up-regulate NTF mRNAs and NTF production in culture with axolemma-enriched fraction. ELISA and RT- PCR will measure OEC NTF levels in interaction with neuron membranes. 3) OECs increase the amount of regeneration-associated genes in motorneurons after injury. In situ hybridization will be used to determine if OECs affect gene expression after transplant into a SCI.
| DeLucia, Tracey A; Alexander, Thomas D; Fargo, Keith N et al. (2007) Effects of single versus combinatorial treatment strategies on beta II-tubulin gene expression in axotomized hamster rubrospinal motoneurons. Restor Neurol Neurosci 25:573-84 |
