Spinal cord injury (SCI) is a devastating condition characterized by the loss of neuronal pathways responsible for coordinating motor and sensory information between the brain and the rest of the body. The mammalian spinal cord is limited in its ability to repair itself, so treatments devised to replace damaged tissue and promote regeneration are essential towards developing a cure. This work describes the development of a guidance channel strategy for spinal cord transection. Chitosan guidance channels were designed as a delivery vehicle for neural stem/progenitor cell (NSPC) transplants and drug-eluting poly(lactic-co-glycolic acid) (PLGA) microspheres. PLGA microspheres were embedded into chitosan channels by a spin-coating method. These microsphere-loaded channels demonstrated the ability for controlled short-term bioactive release of the small molecule drug dibutyryl cyclic-AMP (dbcAMP) and long-term bioactive release of the protein alkaline phosphatase. NSPCs were shown to be responsive to dbcAMP delivery, which results in greatly enhanced differentiation into neurons. The effect of directed neuronal differentiation was investigated after spinal cord transection in rat, resulting in a dramatic increase in NSPC transplant survival. Guidance channels containing NSPCs treated with dbcAMP resulted in robust tissue bridge formation after SCI, demonstrating extensive axonal regeneration and promoting functional recovery.
| Identifer | oai:union.ndltd.org:TORONTO/oai:tspace.library.utoronto.ca:1807/31804 |
| Date | 10 January 2012 |
| Creators | Kim, Howard |
| Contributors | Shoichet, Molly, Tator, Charles |
| Source Sets | University of Toronto |
| Language | en_ca |
| Detected Language | English |
| Type | Thesis |
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