Regenerating axons within the central nervous system (CNS) remains a fundamental challenge in neuroscience. Recently, we have shown that a large number (10/5) of axons integrated with CNS neuronal cultures will grow rapidly (8-10 mm/day) and over long distances ( >5 cm) if the axons are placed under a continuous mechanical tension. We feel the impact of this discovery could be significant. This technique provides a method to culture cell transplants for bridging lesions in the white matter that are centimeters long, distances that are not readily traversed with such a large number of axons using other techniques (e.g., ensheathing cell transplants, directed material scaffolds, controlled release). In addition, this model represents an opportunity to study the mechanisms of accelerated axonal growth in a large population of axons that was previously not possible. However, the technology is at a critical nascent stage with risk - it is not widely used or available to investigators, and we do not know if axonal tracts developed with this technique have viable electrophysiological function. In this proposed, we will build the appropriate technical infrastructure for rapidly culturing a large number of cell transplant constructs using commercially available materials, creating a more generalizable resource for the neuroscience community. Embedded within this re-design of the system is to allow for the measurement of electrophysiological properties of the constructs. Once developed, we use this to propose a series of studies on how a specific cytoskeletal component (neurofilaments) may be a key limiting factor in controlling the growth rate with this technique.
| Pfister, Bryan J; Iwata, Akira; Taylor, Andrew G et al. (2006) Development of transplantable nervous tissue constructs comprised of stretch-grown axons. J Neurosci Methods 153:95-103 |
| Pfister, Bryan J; Iwata, Akira; Meaney, David F et al. (2004) Extreme stretch growth of integrated axons. J Neurosci 24:7978-83 |
