The invention relates to culturing motor neuron cells together with skeletal muscle cells in a fluidic device under conditions whereby the interaction of these cells mimic the structure and function of the neuromuscular junction (NMJ) providing a NMJ-on-chip. Good viability, formation of myo-fibers and function of skeletal muscle cells on fluidic chips allow for measurements of muscle cell contractions. Embodiments of motor neurons co-cultures with contractile myo-fibers are contemplated for use with modeling diseases affecting NMJ's, e.g. Amyotrophic lateral sclerosis (ALS).

Systems and methods for producing and using a body having a first structure defining a first chamber, a second structure defining a second chamber, a membrane located at an interface region between the first chamber and the second chamber to separate the first chamber from the second chamber. The first chamber comprises a first permeable matrix disposed therein and the first permeable matrix comprises at least one or a plurality of lumens each extending therethrough, which is optionally lined with at least one layer of cells. The second chamber can comprise cells cultured therein. The systems and methods described herein can be used for various applications, including, e.g., growth and/or differentiation of primary cells, and/or simulation of a microenvironment in living tissues and/or organs (to model physiology or disease states, and/or to identify therapeutic agents). The systems and methods can also permit co-cultures of two or more different cell types.

Described herein are methods for generating human forebrain endothelial cells, compositions comprising the cells, and methods of use thereof in therapy. Provided herein are methods for generation of human embryonic forebrain-like endothelial cells (e.g., periventricular endothelial cells) from human embryonic stem cells; the methods include addition or GABA and WNT7A for efficient differentiation, and isolation of GABRB37CD31+ cell population by FACS.

Provided herein are methods and compositions related to the use of human monocyte-derived microglia-like (MDMi) cells. In some embodiments, the methods and compositions provided herein relate to the use of MDMi cells to assess the effect of a clinical intervention on a human subject (e.g., a subject with a neurodegenerative disorder). In some embodiments, the methods and compositions provided herein relate to the use of MDMi cells to stratify human subjects into subgroup populations (e.g., populations that are likely to respond to a clinical intervention or are unlikely to respond to a clinical intervention). In some embodiments, the methods and compositions provided herein relate to the use of MDMi cells to identify candidate neurodegenerative disease biomarkers. In certain embodiments, the methods and compositions provided herein relate to the use of MDMi cells to screen potential therapeutic agents to identify candidate agents for the treatment of a neurodegenerative disease.

The invention relates to culturing brain endothelial cells, and optionally astrocytes and neurons in a fluidic device under conditions whereby the cells mimic the structure and function of the blood brain barrier. Culture of such cells in a microfluidic device, whether alone or in combination with other cells, drives maturation and/or differentiation further than existing systems.

The present invention relates to a method for differentiating a spherical neural mass (SNM) into retinal outer layer cells, and a composition containing the retinal outer layer cells prepared by the differentiation method. If the differentiation method of the present invention is used, the SNM can be efficiently differentiated into retinal outer layer cells, and thus the present invention can be effectively used in research development and commercialization related thereto.

Functional, brain region-specific neural spheroids comprising neuronal cells and optionally glial cells at varying ratios are disclosed, as are methods of making such spheroids and methods for their use, such as for modeling particular brain regions that may be implicated in diseases, or for observing drug effects.

Disclosed is a process of manufacturing cell spheroids using a bioink. More particularly, provided is a method of manufacturing a cell spheroid, the method including extruding a first bioink including an alginate; extruding a second bioink including cells into the extruded first bioink; adding a calcium chloride (CaCl2) solution to the alginate included in the first bioink; and dissolving the second bioink, present in the first bioink, in a cell culture medium to form a cell spheroid from the cells.

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.

Provided herein is an in vitro model of the blood brain barrier. In some embodiments, the model includes: an endothelial cell layer, and brain tissue layer comprising neuronal cells, and optionally one or more of astrocytes, pericytes, oligodendrocytes, and microglia. In some embodiments, the model further comprises a porous membrane between said endothelial cell layer and the neuronal cell layer. A microfluidic device comprising the same and methods of use thereof are also provided.