Glial Cells

Reactive astrocyte activity on a material is an indicator of how well the material will minimize undesirable glial scarring after implantation. This is relevant for CNS applications of neural tissue scaffolds and also for evaluating materials from which microelectrodes will be fabricated. As with many other in vitro studies, cell adhesion and proliferation are strong indicators for cell activity associated with a material. This is particularly relevant for astrocytes due to their tendency to proliferate after CNS injury. Again, an ideal material for a CNS implant will reduce astrocyte adhesion and proliferation. Rat astrocytes are commonly used in experiments (CRL-2005, American Type Culture Collection, Manassas, VA). Proteins associated with astrocyte activity, such as glial fibrillary acidic protein (GFAP) can also be labeled and imaged with immunocytochemistry techniques to evaluate cell activation.

Schwann cell activity is relevant for neural cell scaffold applications in the PNS due to their presence, but it is also relevant in the CNS due to regeneration approaches that use transplanted Schwann cells to promote CNS activity and myelinate regenerating CNS axons (Huang and Huang 2006). Oligodendrocytes and olfactory ensheathing cells, too, are known to form an endoneurial sheath for growing axons and have been identified as candidates for cell transplants. Schwann cells, which promote tissue regeneration in the PNS, and olfactory ensheathing cells have been shown to enhance nerve regeneration when transplanted into the CNS (Ramon-Cueto and Valverde 1995; Schmidt and Leach 2003). The morphology of Schwann cells has been shown to be an important factor in axon guidance.

Polymer molds of Schwann cells alone have been shown to guide growing axons (Bruder et al. 2007). This stresses the importance of topography of neural tissue scaffold and also the role of supporting cells in nerve regeneration strategies.

Co-cultures of relevant cell types can provide insight into how cells will interact with a material and also interact with each other. Once implanted into the body, the material will be exposed to a number of cell types in the local environment. These cells may compete to adhere to the material surface. A co-culture is a more physiological in vitro assay because it more accurately reproduces the conditions to which the material will be exposed. Different cell types, most notably the interaction between Schwann and neural cells, also produce biochemical cues which may influence cell behavior. Trophic factors, such as BDNF, are axon chemoattrac-tants produced by Schwann cells (Meyer et al. 1992). Assays to investigate competitive adhesion or cell organization on a material's surface can provide insight into how the neural tissue will interact with the implant. Glial markers produced by Schwann cells have been studied with immunocytochemistry techniques (Corey et al. 2007).

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