Tissue Engineering of Rodent Optic Nerves as a Model for Myelination

Lead Research Organisation: University of Leeds
Department Name: Institute of Membrane & Systems Biology

Abstract

The development and proper functioning of the human central nervous requires that we develop insulation for long nerve fibres called axons. In many ways this is similar to the insulation required to make electrical wires function correctly. A special type of cell called an oligodendrocyte is responsible for providing this insulation in the form of a substance we call myelin. There are some diseases where the myelin either does not form correctly, such as cerebral palsy, or where myelin breaks down later in life, such as multiple sclerosis. If the causes of these diseases and the loss of myelin are to be identified scientists require model systems that allow them to experiment with developing oligodendrocytes and thereby identify the key factors that affect them. This proposal is for a program of research to culture white matter, the type of tissue found in the brain where myelination occurs, so that the mechanism of myelination can be discovered in its native environment. To achieve this biologists will work with engineers to create a new piece of equipment that is purpose built for the project.

Technical Summary

Myelination is a complex process that cannot be modeled using unicellular culture of oligodendrocytes and the production of myelinating cell cultures is difficult, time consuming and still does not truly model myelination as it occurs in vivo. We propose a cross discipline collaboration between the laboratories of Dr. M G Salter of the Faculty Biological Sciences and Dr Sotirios Korossis of the School of Mechanical Engineering, both at Leeds University, to create a unique culturing system designed to model white matter development in a way that is amenable to genetic modification and scientific study. When complete this system will allow us to successfully culture an optic nerve from the pre myelinating stage through myelination to a point where it is fully myelinated and will be available as an experimental model for both myelination and injury. The technology developed will be used as the basis for future applications for funding that look to investigate the effect of re perfusion following ischemic challenge, the effect of ablation of developmental proteins involved in myelination and for morphological investigation of the process of myelination. It is important to note that this will not just be proof of principle for this particular system. By using tissue engineering to develop a more functionally relevant a model system we will be providing a proof of principal for others working on complex tissue types who are currently using simplified mono cellular culture systems as models.

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