2013 Participants
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NAME: Arrin Carter

PROJECT TITLE: Biological Engineering of a Neural Migratory Stream

The long-term goal of this proposal is to provide mechanistic insight into the
regenerative capacity of the adult mammalian brain, using a truly unique and potentially transformative approach which involves the bioengineering of neural cell migratory streams. These streams are paths taken by endogenous neural progenitor cells as they migrate from their birthplace to their final site of integration. For example, the rostral migratory stream is a migratory route from the subventricular zone (SVZ) to the olfactory bulb. The technology involves the generation of small (0.7 mm O.D.) cylinders consisting of a biocompatible-biodegradable matrix (fibrin) containing neurotrophic factors of interest (e.g., BDNF, GDNF, etc.) and/or extracellular matrix (e.g., laminin, collagen, etc.) and/or specific cell types (e.g., neural stem cells, endothelial cells, etc.). In addition to containing uniform concentrations of
either covalently bound or unbound soluble factors, a method has been developed which facilitates the generation of concentration gradients of factors through the length of the cylinder. A third (and the most novel) permutation of the method involves making a “cylinder-in-cylinder” (CinC) where a second, smaller (0.33 mm O.D.) cylinder is cast along the inside length of the larger 0.7 mm O.D. cylinder, thus allowing two biological matrices with different factors/ECMs/cells to be intimately juxtaposed. This recapitulates the complexities of in vivo neural architecture such as the rostral migratory stream, where vascular and distinct neural cell types coexist. These “engineered migratory streams” (EMS) are evaluated in vitro for
their influence on the migration and differentiation of cultured SVZ derived adult neural stem cells, and, complementing this cell culture approach, they are implanted into rat brain to determine the invivo capability of the EMS to direct endogenous neural stem cell migration and development over a several week period.

To view Arrin's website click here