The present invention relates to in vitro models of autism and methods of using the same to diagnose disorders associated with network dysfunction, e.g., autism schizophrenia, depression, obsessive-compulsive spectrum disorders, bipolar disorder, or epilepsy, and to identify compounds for use in treating these conditions.

The invention provides a cell-containing vessel comprising a plurality of neural cell-containing spheroids for which the variation calculated using the calculation method described below is less than 20%, wherein the neural cell-containing spheroids contain a plurality of types of cells including neural cells,

Calculation Method

Calcium transient assays are conducted for each of a plurality of neural cell-containing spheroids, a number of spontaneous oscillations in a 10-minute period is measured, an average and standard deviation for the number of spontaneous oscillations are calculated, and a variation is calculated using formula (1) below:

[00001]$\begin{array}{cc}\mathrm{Variation}\left(\%\right)=\mathrm{standard}\mathrm{deviation}\mathrm{for}\mathrm{number}\mathrm{of}\mathrm{spontaneous}\mathrm{oscillations}/\mathrm{average}\mathrm{number}\mathrm{of}\mathrm{spontaneous}\mathrm{oscillations}100.& \left(1\right)\end{array}$

Provided are layered cell sheets, comprising a plurality of layered cell sheets containing myoblasts, in which each cell sheet comprises cell population containing myoblasts with controlled orientations. Preferably provided are the layered cell sheets comprising a region in which the orientations of the cell population containing the myoblasts in each cell sheet are identical to each other.

A method for forming neuromuscular junctions includes forming functional neuromuscular junctions between motoneurons and muscle cells by co-culturing one or more human motoneurons and one or more rat muscle cells in a substantially serum-free medium. A synthetic mammalian neuromuscular junction includes a human motoneuron functionally linked to a rat muscle cell in a substantially serum-free medium. An artificial substrate may be used to support the one or more neuromuscular junctions.

The disclosure relates to a system and method of using the system to detect and monitor afferent synaptic nerve fiber function in vitro. The disclosure also relates to a method of screening for test agents or compounds that modulate nerve function, such as test agents that modulate pain sensation in a human subject, by exposing one or a plurality of test agents to systems comprising a first and second spheroid, wherein the first spheroid comprise cells from a mammalian dorsal root ganglia and the second spheroid comprises cells from a mammalian spinal cord.

The invention relates to an in vitro cell culture comprising neuronal cells derived from iPSC, optionally with an NGN2 transgene, astrocytes derived from iPSC with a SOX9 transgene, and oligodendrocytes derived from iPSC with a SOX10 transgene.

Synthetic human blood vessels can be constructed using human brain derived endothelial cells and incorporated into a tissue model that contains astrocytes and other neurons and microglia. Multi-cell type microvessels incorporate cell types such as astrocytes and pericytes in order to construct a highly representative blood-brain barrier in vitro model with a functional lumen containing brain-derived microvascular endothelial cells and a polymer wall containing human astrocytes and/or pericytes.

Hair follicle bulge region/LLP region CD34(+) MeSCs can be isolated from mammalian skin bearing hair follicles. These cells are multipotent and retain the ability to differentiate into cells of neural crest lineage, including glia-like cells that express the glial marker Gfap, and are able to express myelin basic protein, and to remyelinate naked (unmyelinated or demyelinated) neuronal processes with a functional, dense myelin sheath. These cells of neural crest lineage can be used to produce a dense myelin sheath on neurons which lack myelin due to genetic defect, trauma, toxin, infection, or disease process. Therefore, embodiments of the invention provide methods for preparing such cells, the cells themselves and compositions containing the cells, as well as methods for using the cells.

The present invention relates to a kit comprising a co-culture microdevice containing peripheral sensory neurons (PSN) and human epidermal keratinocytes (HEK) in a cell culture adapted for both cell types. It is also described a method for screening an active compound using the kit according to the present invention, as well as the use thereof for in vitro drug tests and for producing a cosmetic product for various dermatological applications, such as atopic dermatitis, sensitive skin, photoaging, wound healing and epidermal thickness in aged skin.

This disclosure relates to methods and compositions useful for culturing astrocytes, producing astrocytes, expanding astrocytes, or promoting astrocyte development. In certain embodiments, this disclosure relates to cell culture compositions comprising components disclosed herein. In certain embodiments, this disclosure relates to methods of culturing astrocytes, promoting astrocyte development, or producing astrocytes comprising contacting a cell, stem cell, induced pluripotent cell, astrocyte, pre-astrocyte cell, or tissue with proteins BMP4, TGF-2, TSLP, DKK1, and NLGN1 providing astrocytes.