Surface Topography During Neural Stem Cell Differentiation Regulates Cell Migration and Cell Morphology

Abstract

We sought to determine the contribution of scaffold topography to the migration and morphology of neural stem cells by mimicking features of scaffolds found in vivo. We mimicked two types of CNS scaffolds encountered by neural stem cells during development in vitro by constructing different diameter electrospun polycaprolactone (PCL) fiber mats, a substrate that we have shown to be topographically similar to brain scaffolds. We compared the effects of large fibers (made to mimic blood vessel topography) with those of small diameter fibers (made to mimic radial glial process topography) on the migration and differentiation of neural stem cells. Neural stem cells showed differential migratory and morphological reactions with laminin in different topographical contexts. We demonstrate, for the first time, that neural stem cell biological responses to laminin are dependent on topographical context. Topography‐induced cell morphology changes were inhibited by nocodazole, but not by cytochalasin‐D or ROCK‐inhibitor, suggesting that microtubule function is necessary for topography‐induced morphology changes. We propose that the physical structure of distinct scaffolds induces unique signaling cascades that regulate migration and morphology in embryonic neural progenitor cells.Support or Funding InformationBS acknowledges Pelotonia Foundation Undergraduate Research Fellowship. AS acknowledges The Ohio State University/Metro High School Graduate Teaching Assistant Fellowship. The project described was supported by Award Number Grant 8UL1TR000090‐05, from the National Center for Advancing Translational Sciences. The content is solely the responsibility of the authors and does not necessarily represent official views of the National Center for Advancing Translational Sciences or the National Institutes of Health. This work was sponsored by and represents activity of The Ohio State University Center for Regenerative Medicine and Cell Based Therapies (regenerativemedicine.osu.edu).