Effect of Laminin Derived Peptides IKVAV and LRE Tethered to Hyaluronic Acid on hiPSC Derived Neural Stem Cell Morphology, Attachment and Neurite Extension

Low neural tissue extracellular matrix (ECM) content has led to the understudy of its effects on neural cells and tissue. Hyaluronic acid (HA) and laminin are major neural ECM components, but direct comparisons of their cellular effects could not be located in the literature. The current study uses human-induced pluripotent stem-cell-derived neural stem cells to assess the effects of HA, laminin, and HA with laminin-derived peptides IKVAV and LRE on cellular morphology, attachment, neurite extension and ECM remodeling. Increased attachment was observed on HA with and without IKVAV and LRE compared to laminin. Cellular morphology and neurite extension were similar on all surfaces. Using a direct binding inhibitor of Cav2.2 voltage gated calcium channel activity, a known binding partner of LRE, reduced attachment on HA with and without IKVAV and LRE and altered cellular morphology on surfaces with laminin or IKVAV and LRE. HA with IKVAV and LRE reduced the fluorescent intensity of fibronectin staining, but did not alter the localization of ECM remodeling enzymes matrix metalloprotease 2 and 9 staining compared to HA. Overall, the data indicate HA, IKVAV and LRE have complementary effects on human-induced pluripotent stem-cell-derived neural stem cell behavior.