Can we force axons to grow?

We also investigate how to use mechanical forces to promote growth, rather than cause injury, in the nervous system. We apply small, continuous force to cultured neurons in order to induce the growth of axons from these neurons over fairly long distances. When these low forces are applied, the neurons will respond by growing their axonal projections to accommodate the length. We have developed an apparatus to focus these forces on the neuritic processes of cells, and have developed a culture of two intact neuronal cell populations that have interconnecting neurites between the populations. (Click on this link to see one of the papers that we published using this technique.)

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Axons are grown between two clusters of cell bodies, where both the rate and the final distance of growth is controlled. The thin connections between the two clusters of cell bodies in the picture does not represent an individual axon, but rather several hundred to thousands of axons that are forming an axonal tract between the two populations. The dime is used as a reference for the length of the tissue construct - the axons in this experiment were grown to a final distance of 5 cm.

The distances that we can force axons to grow using this new method is considerable - recent work has grown cultures of axons between two poulations of neurons nearly 5 cm! The capacity to grow axons such a long distance is very exciting, since it now offers a new tool to develop tissue transplants for the nervous system that can bridge long distances. Currently, alternative growth strategies are successful in only bridging much shorter distances in the nervous system. We are examining how to improve this technique, and use this model system to study the molecular 'signature' of growth in cultured neurons. As such, this tool represents a potential 'reverse engineering' approach for repair and regeneration in the nervous system. Steve Bernstein, a new member of the lab, is pursuing the optimization of this technology, as well as finding some of the unique molecular steps that occur when axonal growth is accelerated to this level.