Since the advent of stem cell biology, the brain and spinal cord have been intensively investigated as potential targets of stem and progenitor cell-based therapies. The CNS would seem a promising target for cell replacement therapy, in light of the plethora of diseases of the human nervous system, the overall lack of effective therapeutic approaches for most brain diseases, and the great store of developmental information available on the ontogeny of neurons and glia that can be applied to generate clinically relevant cell types. Yet the brain is an especially difficult organ in which to employ stem cell-based therapeutics. The phenotypic heterogeneity and myriad connections of its neuronal elements, the four dimensional complexity of its synaptic architecture, and the regionally-variable and poorly understood nature of neuronal interactions with astrocytes, oligodendrocytes and glial progenitor cells, all conspire to defy precise structural reconstitution.
