Functionality of neuronal networks derived from human embryonic stem cells

Abstract

In this paper, we describe methods for studying the maturation of human embryonic stem cell (hESC) -derived neuronal networks. The production of functional hESC-derived neuronal cells is critical for their application in treat ing neurodegenerative disorders. Microelectrode array technology allows measuring the electrophysiological activity of the cells while the network maturates. Our results indicate that the hESC-derived neuronal networks were spontaneously active and exhibited time dependent maturation in recorded electrical impulse firing patterns starting from spontaneous random spiking and eventually maturating into bursting activity. Immunocytochemical studies revealed that these networks were positive for the neuronal marker microtubule-associated protein 2 (MAP-2) and glial fibrillary acidic protein (GFAP). The formed networks responded to modulation with sodium-ion channel, glutamate and GABA receptors affecting substances, indicating that pharmacologically susceptible neuronal networks with functional synapses had been generated. The findings indicate that hESC-derived neuronal cells can generate communicating networks and are therefore suitable for use in developmental and drug screening studies, and potentially for regenerative medicine in the future. © 2009 Springer-Verlag.