Disclosed are formulations and procedures to improve the accuracy of nonanimal tests. Disclosed procedures involve both the direct application of the substance to be tested to the excised eye or other suitable test matrix, such as a differentiated tissue, and the application of an aqueous layer to the apical surface and then the addition of the substance to be tested as an overlay to the aqueous layer for a period of time so as to allow metabolism of the substance to be tested by the eye or test matrix, but not so long as to result in nonirritant or nontoxic test substance resulting in a FP result.

The invention provides methods for treating pathological conditions associated with an undesirable inflammatory component. The invention is generally directed to reducing inflammation by administering cells that modulate microglia activation. The invention is also directed to drug discovery methods to screen for agents that modulate the ability of the cells to modulate microglia activation. The invention is also directed to cell banks that can be used to provide cells for administration to a subject, the banks comprising cells having desired levels of potency to modulate microglia activation.

Techniques and systems are disclosed for a bioassay that is an in vitro mimic of peripheral nerve generation using the sensory neurons that innervate the peripheral nervous system. In some embodiments, the techniques may assist in detecting the bioactivity or potency of nerve grafts (e.g., processed, acellular human allografts) for fostering or supporting peripheral nerve regeneration. In various embodiments, techniques comprise affixing neurons (e.g., a DRG) to a nerve graft segment to form a test construct; culturing the test construct in a medium; analyzing the test construct to indicate the amount of outgrowing nerve structure; and determining the potency of the nerve graft from a metric derived from the analysis. In some embodiments, techniques and materials may be used to test the effect of a varied test condition on nerve growth.

The purpose of the present invention is to efficiently produce microglia from pluripotent stem cells. Provided is a method for producing microglia from pluripotent stem cells, comprising the following steps: (a) a step of co-culturing a pluripotent stem cell together with a feeder cell for 7 days or longer, and obtaining a blood progenitor cell; (b) a step of co-culturing the blood progenitor cell obtained in step (a) together with a feeder cell in the presence of IL-3 and/or GM-CSF, and obtaining an embryonic monocyte; and (c) a step of, in the presence of M-CSF, co-culturing the embryonic monocyte obtained in step (b) together with an astrocyte, or culturing the embryonic monocyte using an astrocyte supernatant.

A method for treating a subject with depression characterized by having an increased burst firing in neurons of a lateral habenula in the subject is provided. The method includes a step of administering to the subject a pharmaceutical composition capable of inhibiting the burst firing in the lateral habenula of the subject. The pharmaceutical composition includes one or more active pharmaceutical agents, which can suppress the burst firing in the lateral habenula of the subject and can include at least one of an N-methyl-D-aspartate receptor (NMDAR) inhibitor or a T-type calcium channel inhibitor. The pharmaceutical composition can be in a formulation allowing for local administration to the lateral habenula of the subject, or can be in a formulation configured for systemic administration to the subject. A method for testing a test substance for an antidepressive effect is also provided.

Cell-based sensor devices, systems, and methods for the detection and identification of volatile compounds, and for the determination of the location of the source of the volatile compounds in an enclosed space are described.

The method for producing a cell aggregate including glial progenitor cells according to the present invention comprises: (1) a step of subjecting pluripotent stem cells to suspension culture in an embryoid-body-forming culture medium containing one or more SMAD signaling inhibitors and one or more Wnt signaling activators in the absence of feeder cells for 5 days to 10 days, to form a cell aggregate; (2) a step of subjecting the cell aggregate obtained in (1) to suspension culture in an embryoid-body-forming culture medium containing retinoic acid; (3) a step of subjecting the cell aggregate obtained in (2) to suspension culture in an embryoid-body-forming culture medium or neuron-and-glia-proliferating culture medium containing retinoic acid and one or more SHH signaling activators; and (4) a step of subjecting the cell aggregate obtained in (3) to suspension culture in a neuron-and-glia-proliferating culture medium containing no retinoic acid and one or more SHH signaling activators.

A method for inducing a hibernation-like state and a device for the same is described. The method is a chemical and physical method for reducing, in a subject, a theoretical set-point temperature of a body temperature and/or a feedback gain of heat production, or for inducing a hibernation-like state in the subject, the method including applying an excitatory stimulus to pyroglutamylated RFamide peptide (QRFP)-producing neurons. A device used to implement the method is also described.

Objects to be achieved are to provide a nerve cell with which it is possible to visualize and quantify the intracellular tau without using the exogenous promoter and to provide a pluripotent stem cell with which the nerve cell can be produced, to provide a method of screening a substance, including using the pluripotent stem cell or nerve cell described above, and a substance screened by the above method, and to provide a kit including a targeting vector and a gRNA.

There is provided a pluripotent stem cell including a DNA encoding a reporter molecule, the DNA being introduced adjacent to an endogenous tau gene such that a tau protein is expressed as a fusion protein fused with a reporter molecule.

This disclosure relates to methods for expanding inner ear supporting cells (e.g., Lgr5+ inner ear supporting cells) and differentiating inner ear supporting cells (e.g., Lgr5+ inner ear supporting cells) to inner ear hair cells (e.g., atonal homolog 1 (Atoh1)+ inner ear hair cells) and the use of the inner hear supporting cells and hair cells, e.g., for identifying candidate therapeutic compounds for the treatment of hearing loss and balance loss. Additionally, the methods described herein can be used in the treatment of a subject having hearing loss and balance loss that would benefit from increased proliferation and differentiation of inner ear supporting cells (e.g., Lgr5+ inner ear supporting cells).