2003 Director's Summary Synopsis

TECHNOLOGIES FOR ADVANCING TO CLINICAL APPLICATION
Martin Oudega, Ph.D. • Mary Bartlett Bunge, Ph.D. • Allan D.O. Levi, M.D.

One of the challenges of taking a promising repair strategy from animal experiments to human trials is to find ways to accurately evaluate the efficacy of a strategy once it is applied in humans. Schwann cell (SC) transplantation has been shown to promote nerve fiber regeneration in spinal injury in animals. In future human trials, researchers will need ways to identify cells after transplantation so they can obtain vital information about their effectiveness. Dr. Allan Levi and his colleagues sought to establish a simple, reliable method of labeling SCs. After labeling the SCs with a fluorescent marker, CFSE, they observed the labeled SCs in culture dishes as well as after transplantation into animals. Their results show that the SCs retained the fluorescent marker for at least four weeks.

In addition to the potential use of SCs, various studies suggest that neurotrophins applied to the spinal cord promote reentry of axons into the spinal cord beyond SC bridges. Looking to apply this knowledge in future human trials, Miami Project researchers are developing and testing feasible techniques for the delivery of neurotrophins. While one option for delivery of neurotrophins is to inject them directly into the spinal cord, this method may cause further damage to spinal cord tissue. Miami Project scientists, Bas Blits, Ph.D., Martin Oudega, Ph.D. and Mary Bartlett Bunge, Ph.D. have tested an alternative delivery method using a minimally invasive injection containing viral vectors. The viral vector, a genetically modified virus containing a therapeutic gene, infects cells in the spinal cord and transfers a new gene message for the cell to produce neurotrophins. Their recent study was a first attempt to combine viral vector delivery of neurotrophin genes with SC bridges. They found that the neurons did produce the specific neurotrophins; however, further studies will be required to determine the best combination of regeneration strategies to achieve reentry of axons into the spinal cord from within the SC bridge.

Synopsis Publications

 Li X, Dancausse H, Grijalva I, Oliveira M, Levi ADO (2003) Labeling Schwann cells with CFSE-an in vitro and in vivo study. J Neurosci Methods 125:83-91. .

 Blits B, Oudega M, Boer GJ, Bunge MB, Verhaagen J (2003) Adeno-associated viral vector-mediated neurotrophin gene transfer in the injured adult rat spinal cord improves hind-limb function. Neurosci 118:271-281.