Described herein is a microphysiological system for models of disease. Specifically, induced pluripotent stem cells (iPSCs) and iPSC-derived cells, including those obtained from disease patients, are seeded onto microfluidic “chip” devices to study cellular development and disease pathogenesis. Herein, neurodegenerative disease modeling, including Parkinson's Disease (PD) is shown to reproduce key PD pathology in a vascularized human model that contains neurons relating to PD pathology. Such compositions and methods are used for research for PD biomarkers, patient screening for PD risk assessment, and therapeutic discovery and testing. A panel of biomarkers are generated through analysis of living PD-chips by neural activity, whole transcriptomic, proteomic, and metabolomic analysis, and functional enzyme tests of media and tissue. Introducing therapeutics through a vasculature channel, coupled with blood brain barrier penetration studies can be assessed for efficacy in the human neural cells present in the PD-Chip.

The present invention provides hypoxia-inducible factor-2α (HIF-2α) as a target in the prevention/treatment of Parkinson's disease (PD). It is the first time to report the target that illustrated mechanisms of iron metabolism in astrocytes, accordingly to confirm the similarities and differences of iron traffic between astrocytes and neurons, leading to indicated the iron source of iron deposition in dopaminergic (DA) neurons and make sure the cause of iron is unevenly distributed in different brain regions, as well as the effects of glias on the role of iron traffic in neurons. It is HIF-2α, regulates the iron traffic in astrocytes. Therefore, not only a new action target HIF-2α is provided for preventing/treating PD iron deposition, but also a brand-new research thought and experimental evidence are provided for the iron transport mechanism of the astrocytes as the high iron source of nerve cells.

The present invention discloses a method of identifying agents that affect human astrocytes functionality using ex-vivo differentiated pluripotent stem cells (PSC). In addition, the use of human progenitor astrocytes or human astrocytes for the treatment of Amyotrophic Lateral Sclerosis (ALS) in a human subject is also disclosed.

The present invention provides a method for producing human A1 astrocytes, which includes inducing human A1 astrocytes from human astrocytes other than human A1 astrocytes; human A1 astrocytes obtained by the method for producing human A1 astrocytes; and a method for evaluating a test substance, which uses the human A1 astrocytes described above. According to the present invention, there is provided the method for producing human A1 astrocytes, which includes a step a of culturing human astrocytes other than human A1 astrocytes in the presence of TNF and IFN.

The present disclosure relates to methods for generating microglial cells derived from stem cells (e.g., human stem cells), microglial cells obtained from such methods and compositions comprising thereof, and uses of said microglial cells for disease modeling and for treating microglia related disorders.

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.

In some embodiments, the present invention provides tissue compositions including a first silk scaffold comprising a plurality of epithelial cells, a second silk scaffold comprising a plurality of stromal cells, and a plurality of neurons. In some embodiments, provided compositions can function as physiologically relevant corneal model systems for, inter alia, testing of therapeutics for corneal disease and/or injury and production of functional corneal tissue (e.g., for transplant, etc). The present invention also provides methods for making and using provided compositions.

The present disclosure generally relates to a cell culturing system, and specifically to a three-dimensional cell culturing system for neuronal cells that promotes both structural and functional characteristics that mimic those of in vivo peripheral fibers, including cell myelination. Using a dual hydrogel construct and spheroids comprising neuronal cells, the present disclosure provides methods, devices, and systems for in vitro spatially-controlled, three-dimensional models that permit intra- and extra-cellular electro-physiological measurements and recordings. The three-dimensional hydrogel constructs allow for flexibility in incorporated cell types, geometric fabrication, and electrical manipulation, providing viable systems for culture, perturbation, and testing of biomimetic neural growth with physiologically-relevant results.

Disclosed is a method of promoting neuronal growth by administering IGFBPL-1, or an agent that increases or stabilizes IGFBPL-1 activity to a subject in need thereof, e.g., a subject in need of treating optic nerve degeneration.

Provided is a structure composed of a cell population comprising endothelial cells, astrocytes and pericytes, and a 3D (three dimensional) cell growth material within which the cell population is located. The structure has a TEER value of at least 450 /cm.sup.2. The cells of the structure may be derived from the brain. The cells may be human cells, and in particular may be primary derived non-immortalised cells. The structure is particularly suited for use in a model of the blood brain barrier, and the invention also provides such a model. The structure is located in a container, in which it separates a first chamber located on a first side of the structure and a second chamber located on a second side of the structure. The first and second chambers respectively contain first and second liquids in contact with first and second sides of the structure. The liquids mimic the brain extracellular fluid and the blood. The blood brain barrier model provided may be used in models of brain disease, and to investigate uptake of agents into the brain or diseased brain.