Combination of IKVAV, LRE, and GPQGIWGQ Bioactive Signaling Peptides Increases Human Induced Pluripotent Stem Cell Derived Neural Stem Cells Extracellular Matrix Remodeling and Neurite Extension.

Extracellular matrix (ECM) remodeling is emerging as a modulator of neural maturation and axon extension. Most studies have used rodent cells to develop matrices capable of manipulating extracellular matrix remodeling for regenerative applications. However, clinically relevant human induced pluripotent stem cell derived neural stem cells (hNSC) do not always behave in a similar manner as rodent cells. In this study, hNSC response to a hyaluronic acid matrix with laminin derived IKVAV and LRE peptide signaling that has previously shown to promote ECM remodeling and neurite extension by mouse embryonic stem cells is examined. The addition of enzymatically degradable cross linker GPQGIWGQ to the IKVAV and LRE containing hyaluronic acid matrix is necessary to promote neurite extension, hyaluronic acid degradation, and gelatinase expression over hyaluronic acid matrices containing GPQGIWGQ, IKVAV and LRE, or no peptides. Changes in peptide content alters a number of matrix properties that can contribute to the cellular response, but increases in mesh size are not observed with cross linker cleavage in this study. Overall, these data imply a complex interaction between IKVAV, LRE, and GPQGIWGQ to modulate hNSC behavior.