Topography, extracellular matrix proteins, secreted molecules and endogenous electric fields: Cues that influence the differentiation of neural progenitor cells

Neural progenitor cells (NPCs) have the potential to be used as a cell based therapy to treat Alzheimer disease, spinal cord injury and other significant damage to the central nervous system. In order to utilize the therapeutic potential of NPCs, we must first learn to control their migration, proliferation, differentiation and growth. An ideal methodology would entail directed stem cell migration to damaged tissue; proliferation until the target is reached; differentiation into the most beneficial phenotype; and integration of cells into the existing tissue. A myriad of stimulants that alter NPC behavior, exist in vivo. Characterizing the individual contributions of each stimulant or cue in vivo can be difficult to deconvolute, unless discerned in vitro. We investigate several of these cues individually and synergistically. We focus on the influence of extracellular matrix proteins, components secreted from surrounding cells in the central nervous system (i.e. - astrocytes, microglia) and the physical micro- and nano-architecture surrounding NPCs. One other stimulus that has not been explored much, but is investigated here extensively, is the influence of electric fields that mimic the electric gradient existent in the developing and adult nervous system. We investigate the contribution of electric fields as stimuli to NPCs and the possible use of electric fields to reap the therapeutic potential of NPCs. In summary, investigation of the influence of a synergistic combination of external cues on the behavior of neural progenitor cells provides insights into their behavior and enables potential control of stem cell differentiation.