Dual Pathway for Promotion of Stem Cell Neural Differentiation Mediated by Gold Nanocomposites

The neural differentiation of embryonic stem cells (ESCs) is of great value in the treatment of neurodegenerative diseases. On the basis of the two related signaling pathways that direct the neural differentiation of ESCs, we used gold nanoparticles (GNP) as a means of combining chemical and physical cues to trigger the neurogenic differentiation of stem cells. Neural differentiation-related functional units (glyco and sulfonate units on glycosaminoglycans, GAG) were anchored on the GNP surface and were then transferred to the cell membrane surface via GNP-membrane interactions. The functional units were able to activate the GAG-related signaling pathway, in turn promoting differentiation and maturation of stem cells into neuronal lineages. In addition, using the photothermal effect of GNP, the differentiation-inducing factor retinoic acid (RA), could be actively delivered into cells via laser irradiation. The RA-related intracellular signaling pathway was thereby further triggered, resulting in strong promotion of neurogenesis with a 300-fold increase in mature neural marker expression. The gold nanocomposites developed in this work provide the basis for a new strategy directing ESCs differentiation into nerve cells with high efficiency and high purity by acting on two related signaling pathways.