In accordance with at least one aspect of this disclosure, an in vitro cell construct includes, a cellular layer including endothelial cells having undergone a biological transformation defining a three-dimensional structure with vasculature formed around basement membrane mimetic gel inner core.

Provided are cortical interneurons and other neuronal cells and in vitro methods for producing such cortical interneurons and other neuronal cells by the directed differentiation of stem cells and neuronal progenitor cells. The present disclosure relates to novel methods of in vitro differentiation of stem cells and neural progenitor cells to produce several type neuronal cells and their precursor cells, including cortical interneurons, hypothalamic neurons and pre-optic cholinergic neurons. The present disclosure describes the derivation of these cells via inhibiting SMAD and Wnt signaling pathways and activating SHH signaling pathway. The present disclosure relates to the novel discovery that the timing and duration of SHH activation can be harnessed to direct controlled differentiation of neural progenitor cells into either cortical interneurons, hypothalamic neurons or pre-optic cholinergic neurons. The present disclosure also relates to compositions of cortical interneurons, hypothalamic neurons or pre-optic cholinergic neurons, and their precursors, that are highly enriched and can be used in variety of application. These cells can be used therapeutically to treat neurodegenerative and neuropsychiatric disorders, and can be used for disease modeling and drug screening.

In one aspect, methods of promoting asymmetric nerve growth and/or regeneration are described herein. In some embodiments, such a method comprises exposing a population of transected or severed nerves to a first molecular growth cue and to a second molecular growth cue. The population of transected nerves comprises one or more nerves of a first nerve type and one or more nerves of a second nerve type differing from the first nerve type. Additionally, the first molecular growth cue preferentially promotes growth of the first nerve type, as compared to the second nerve type. Similarly, the second molecular growth cue preferentially promotes growth of the second nerve type, as compared to the first nerve type. Moreover, the first molecular growth cue is spatially separated from the second molecular growth cue.