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2002 Director's Summary Synopsis

STRATEGIES TO GUIDE REGENERATING FIBERS
Pantelis Tsoulfas, Ph.D. • Jacqueline Sagen, Ph.D. • Daniel J. Liebl, Ph.D.

It is well established that spinal cord fibers have the capacity to regenerate after SCI. One well-known Miami Project strategy using Schwann cell bridges has been effective in promoting axon regeneration. Researchers suspect that significant functional recovery will only occur if the regenerating fibers can make appropriate connections. With current regenerative strategies, regrowth of axons beyond the bridges is limited. The distance that the fibers need to regrow may be a factor that limits their reconnection to target neurons.

Using stem cells to provide a target for regenerating axons has intrigued Dr. Sagen and her colleagues. As a first step in determining the stem cell’s usefulness, the researchers examined whether the transplanted cells would survive. Currently when stem cells are transplanted into the central nervous system, their survival and development are limited. This may be due to a lack of cues in the environment that would support them. By treating the stem cells with neurotrophins (growth promoters), they learned that some stem cells survived. With further research, the combination of Schwann cell bridges with stem cells may be a useful strategy. If the stem cells can serve as targets for nerve fiber growth, this may lead to the repair of spinal cord pathways that control voluntary movement.

Besides using stem cells as targets for fiber growth, Dr. Liebl is interested in learning more about how the molecular environment in the spinal cord influences regeneration. His current studies center on the path that axons take as they develop and how guidance molecules regulate their growth. One family of guidance molecules is the ephrins. They attract or repel axons toward their targets. In a recent study using mutant mice, Dr. Liebl sought to learn the scope of action ephrins exert on the developing nervous system. Data from this type of study may lead to key information regarding the use of guidance molecules to promote regeneration.

Synopsis Publications

 Castellanos DA, Tsoulfas P, Frydel BR, Gajavelli S, Bes J-C, Sagen J (2002) TrkC overexpression enhances survival and migration of neural stem cell transplants in the rat spinal cord. Cell Transplant 11:297-307.

 Liebl DJ, Morris CJ, Henkemeyer M, Parada LF.  mRNA expression of ephrins and Eph receptor tyrosine kinases in the neonatal and adult mouse CNS. J Neurosci Res 2003 Jan 1;71(1):7-22.

 
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