Personalized Human Cortical Spheroids

The recently discovered ability to generate human neurons from somatic cells that have been reprogrammed into pluripotent stem cells provides a novel tool for studying the pathophysiology of neuropsychiatric disorders. We have recently developed a relatively simple approach for generating from human pluripotent stem cells three-dimensional neural spherical structures resembling the human cerebral cortex, which we call human cortical spheroids. These floating spheroids grow up to 5 mm in diameter, and they include deep- and superficial-layer pyramidal neurons arranged concentrically in an inside-outside manner, as well as astrocytes. After developing in culture for ∼10 weeks, cortical spheroids display transcriptional characteristics of late midfetal human cortex. Neurons in these three-dimensional structures display spontaneous electrical activity and form functional synapses, and the emerging neural network activity can be probed in preparations similar to slice recordings of the animal brain. By more accurately reproducing the nervous system milieu, neural spheroids promise to bring novel insights into the unique features of the human cerebral cortex. Ultimately, personalized three-dimensional neural cultures derived from patients with specific psychiatric disorders promise to reveal disease-relevant cellular phenotypes and to provide an in vitro platform for drug screenings.