How Topography Influences the Fate of Human Neural Progenitor Cells

Abstract: Novel biomimetic three-dimensional scaffolds have emerged over the last decades, and are promising for applications in regenerative therapies, as well as in in vitro disease modelling and drug testing. Thanks to their added dimension, these scaffolds are able to more accurately mimic the topography of native cellular microenvironments compared to traditionally used two-dimensional culture substrates. Here we cultured human neural progenitor cells on electrospun fibrous scaffolds in order to investigate how the fibrous topographical landscape influences differentiation capacity and phenotypic fate. In contrast to previous findings, we found that differentiation of progenitor cells cultured on fibrous scaffolds does not differ significantly from that of progenitors cultured on flat glass slides. However, we found that the substrate has a significant effect on the morphology and alignment of cell nuclei. To examine mechanotransductory pathways responsible for interpreting topographical cues into cell responses we cultured cells with the myosin II inhibitor blebbistatin. As there were no differences in differentiation between cells cultured on fibrous scaffolds or glass slides, we could not elucidate any mechanotransductory pathways. Nevertheless, we found that myosin II inhibition led to altered cell and nucleus morphology. Finally, we highlight the need for more consistent methods and continued research on this topic.