Abstract
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.
Highlights
Due to its relatively low content in neural tissue [1], the effects of the extracellular matrix (ECM) on neural cell and tissue function have been understudied
Hyaluronic acid (HA) is a major component of the central nervous system (CNS) ECM [5] that has been used as a backbone polymer for the development of matrices for neural stem cell growth and differentiation [6,7]
matrix metalloprotease (MMP) 2 is associated with axonal regeneration after CNS injury [10,11,12] and ECM remodeling, which is emerging as an important regulator of neural cell behavior and tissue formation [4,13]
Summary
Due to its relatively low content in neural tissue [1], the effects of the extracellular matrix (ECM) on neural cell and tissue function have been understudied. Recent evidence indicates that a number of ECM properties, including biochemical composition, have significant effects on the behavior and function of neural cell types and tissue [2,3,4]. This has significant ramifications for the development of biomaterials to support therapeutic and in vitro models of the central nervous system (CNS). MMP 2 is associated with axonal regeneration after CNS injury [10,11,12] and ECM remodeling, which is emerging as an important regulator of neural cell behavior and tissue formation [4,13]. Understanding how each molecule contributes to cellular response would be beneficial in the rational development of biomaterial supports for neural cultures
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