Archives—December 2010

Engineering Microenvironment for Neurogenesis

Friday, December 3
U113 M&M Building
11:00 am

Presenter: Li Yao, Ph.D., National Center for Biomedical Engineering Science, National University of Ireland, Galway, Ireland

Abstract: Advances in neuroscience over the past two decades begin to offer hope for patients with injury in nervous system. Since the demonstration in 1980 that central  nervous system axons have the capacity to regenerate within peripheral nervous system graft, much has been accomplished toward understanding factors that contribute to a physiologically permissive environment. Axonal regeneration after injury or disease is the major challenge in both peripheral and central nervous system. Neural engineering is a promising approach for axonal regeneration by preventing inhibitory factors and enhancing guided axonal growth. In peripheral nerve regeneration, neural conduits have been investigated to bridge nerve defects. In our recent study, the advance in the design of engineered scaffolds that mimic peripheral nerve multiple basal lamina have improved guided axonal regeneration in vivo. Despite recent advances, the limited demonstration of functional improvement in in vivo models of spinal cord injury has prevented advancement of regenerative therapy to clinical use. This may be due in large part to the multifaceted nature of spinal cord injuries, which presents a major challenge to therapeutic development. In order for viable treatment strategies to be realized clinically, it is likely that combinations of current therapeutic approaches must be used. We are developing a functionalised graft that targets injury mechanisms at the molecular, cellular and tissue levels of spinal cord  injury. Biodegradable polymers can simultaneously provide structural guidance at a cellular level and a reservoir  for sustained gene delivery. This integrative approach suggests a possible treatment strategy and may serve as an in vivo model for studying optimisation of various combinations of treatments.  Effectively directed neuron migration is critical for development and repair in the central nervous system. Endogenous electrical signals are present in many developing systems and crucial cellular behaviours such as neuronal cell division, cell migration and cell differentiation are all under the influence of such endogenous electrical cues. Pre-clinical in vivo studies have used electric fields to attempt to enhance re-growth of damaged spinal cord axons with some success. We recently demonstrated that small electric fields not only guide axonal growth, but also can direct the earlier events of neuronal migration and neuronal cell division. This raises the possibility that applied or endogenous electric fields, perhaps in combination, may direct transplanted neural stem cells, or regenerating neurons, to the desired site after brain injury or neuron degeneration. The high complexity of both structure and function of the central nervous system however, poses significant challenges to techniques for applying electric fields to promote neurogenesis. The evolution of functional biomaterials and nanotechnology may provide promising solutions for the application of electric fields in guiding neuron migration in neurogenesis within the central nervous system.