Enhanced\nMigration of Neural Stem Cells by Microglia\nGrown on a Three-Dimensional Graphene Scaffold

Abstract

One of the key challenges\nin engineering neural tissues for cell-based\ntherapies is to develop a biocompatible scaffold material to direct\nneural stem cell (NSC) behaviors. One great advantage for a scaffold\nwould be to induce NSC migration toward pathological sites during\nregeneration and repair. In particular, the inflammatory responses\nin the pathological zone, which are mainly mediated by microglia in\nthe central nervous system, affect the repair capacity of NSCs through\nNSC migration. Recently, graphene was used as a neural interface and\nscaffold material, but few studies have addressed the relationship\nbetween microglia and NSCs in a graphene culture system. In this study,\nwe used a combination of immunofluorescence, Western blotting, enzyme-linked\nimmunosorbent assays, and scanning electron microscopy to investigate\nhow conditioned medium (CM) produced from microglia grown on two-dimensional\ngraphene (2D-G) films or three-dimensional graphene (3D-G) foams govern\nNSC migration. The results revealed that the CM produced by microglia\ngrown in 3D-G cultures could promote neurosphere formation, facilitate\nNSC migration from the neurospheres, and increase single cell polarization\nby activating the stromal cell-derived factor 1 α (SDF-1α)/CXC\nchemokine receptor 4 (CXCR4) signaling pathway and enhancing cell\nadhesion on the substrate. By contrast, the 2D-G CM failed to achieve\nthese results. Our study suggests the great potential of 3D-G as a\nneural scaffold for NSC-based therapy in tissue engineering and regenerative\nmedicine.