The present invention discloses, in one embodiment, a method of using human induced pluripotent stem cells to generate three-dimensional human organ tissue for therapeutic drug toxicity and discovery⋅. In one embodiment, a high throughput microtiter plate is loaded with both wild type and Rett disease 3D spheroids and exposed to a drug library, and activity is measured and analyzed for disease rescue to wild type cell behavior.

Disclosed herein is a device comprising a microelectrode comprising cells cultured on a surface of the microelectrode and a porous membrane comprising an upper surface comprising cultured cells. Further, devices and methods for in in-vitro models of the blood-brain barrier (BBB) and for modeling the transport across this barrier are disclosed.

Compositions and methods are provided for biologically relevant in vitro screening of neural function, including determination of the effects of an agent on neural cells. The compositions of the invention useful in such screening methods include a neural co-culture system comprising human pluripotent stem cell (PSC)-derived neurons and human glial cells, which may be derived by culture methods allowing for rapid and robust development of highly mature neuronal activity, particularly spontaneous synchronous network bursts.

Disclosed is a producing method of a mesenchymal stem cell for brain neuronal disease prevention or treatment including ghrelin treatment, a composition for producing a mesenchymal stem cell for brain neuronal disease prevention or treatment, a mesenchymal stem cell produced by the producing method, and a pharmaceutical composition for prevention or treatment of brain neuronal disease containing the same. When using the producing method of the mesenchymal stem cells with the increased AgRP (Agouti related peptide) expression level according to the present disclosure, the mesenchymal stem cells produced by the method, or ghrelin, various brain neuronal diseases such as Alzheimer's disease may be effectively prevented or treated. When the composition for producing the mesenchymal stem cells with the increased AgRP expression level containing ghrelin according to the present disclosure is used, the mesenchymal stem cells with the increased AgRP expression level may be effectively produced.

The present invention comprises a system and method for co-culturing glia cells and neurons in a combination of glia culture medium and neuron medium wherein the glia cells and neurons have cell morphology, cell reactions and/or cell interactions that exist in vivo after the co-culturing for up to about 21 days, up to about 30 days, up to about 40 days, up to about 45 days. Since the cell morphology, cell reaction and/or cell interaction of the co-culture are similar to those seen in vivo, the present system is capable of being configured as animal models for research, drug screening, testing and conducting clinical trials.

The present invention relates to novel compositions and methods to produce 3D organ equivalents of the brain (i.e. “mini-brains”). The invention also relates to methods of using human induced pluripotent stem cells, a combination of growth and other soluble factors and gyratory shaking. Cells from healthy or diseased donors or animals can be used to allow testing different genetic backgrounds. The model can be further enhanced by using genetically modified cells, adding micro-glia or their precursors or indicator cells (e.g. with reporter genes or tracers) as well as adding endothelial cells to form a blood-brain-barrier.

A cell-containing structure is provided that allows ready-to-use nerve drug response evaluation with high reproducibility to be easily performed. The cell-containing structure for evaluating an electrical property of neurons includes: (a) a culture surface to which the neurons are able to be adhered; (b) a cell mass that is adhered to the culture surface and contains at least one of the neurons; and (c) a plurality of electrodes for measuring the electrical property of the cell mass, wherein a spontaneous firing frequency of cells contained in the cell mass is 0.25 Hz or more per electrode.

Exemplary embodiments provide in vitro brain models, such as in vitro models of a neurovascular unit or a functionally connected trineural pathway, and systems, devices and methods of use thereof. The present invention provides in vitro brain models, systems, devices and methods that mimic in vivo conditions to, for example, determine the effect of a test compound, such as a drug candidate or a toxin, on various biological responses, such as for example, cell viability, cell growth, migration, differentiation and maintenance of cell phenotype, metabolic activity, structural remodeling and tissue level pre-stress, a neural activity, such as an electrophysiological activity.

The disclosure generally relates to methods and compositions for preparing a neural tissue construct. In particular, provided herein are methods for generating a neural tissue construct using glutamatergic cortical progenitor cells; GABAergic interneuron progenitor cells; and bio-ink.

A therapeutic effect of Nurr1 and Foxa2 in inflammatory neurologic disorders by M1-to-M2 polarization of glial cells is provided. Specifically, a method of converting glial cells from an M1 phenotype to an M2 phenotype, wherein Nurr1 and Foxa2 are introduced into the glial cells to be overexpressed in the glial cells and a method of preventing or treating an inflammatory neurologic disorder, which includes glial cells into which Nurr1 and Foxa2 are introduced, or a viral vector loaded with Nurr1 and Foxa2, are provided.