Enhancing Neurogenesis for Brain Tissue Regeneration

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ABSTRACT The regeneration of brain tissue has been considered one of the greatest challenges for regenerative medicine. Only a few invertebrate species spontaneously regenerate brain tissue, but this does not occur in mammals, although a repair response in form of an increased neurogenesis occurs. This neurogenesis provides the cellular substrate required for tissue regeneration. However, tissue regeneration also requires a structural substrates where neural progenitors can integrate and form new tissue. We have demonstrated that bioscaffolds formed out of extracellular matrix (ECM) serve this function when implanted into a stroke cavity. Nevertheless, neuron density in this newly forming tissue is too low and we therefore here propose to: 1) establish optimal conditions for neurogenesis stimulation through growth factor delivery and 2) to exploit this enhanced neurogenesis to re-populate an ECM bioscaffold implanted into the stroke cavity. We expect that this combined approach will increase neuron density in the newly forming brain tissue and this will lead to an improved outcome of behavioral functions. A combined ECM plus neurogenesis stimulation approach can potentially provide a new treatment paradigm for chronic stroke patients. At present, there is no therapeutic intervention that addresses the issue of a tissue cavity in these patients.