The present invention relates to a chemical compound comprising (i) a polycationic polymer, coupled to (ii) a dye. The present invention further relates to a method for visualizing a glycosamine-containing structure in a biological sample comprising a) contacting an inner lumen of said biological sample with a dye-conjugated polycationic polymer, preferably with the chemical compound according to the present invention; b) tissue-clearing said biological sample; and, thereby, c) visualizing an internal glycosamine-containing structure in said biological sample. The present invention also relates to a method for determining the number and/or size of glomeruli in a kidney or a sample thereof making use of the method for visualizing a glycosamine-containing structure; and also relates to kits and uses related to said chemical compounds and said methods.

The disclosure provides a mouse model of arteriovenous malformation, such as found in Hereditary Hemorrhagic Telangiectasia, that accurately and persistently models the disease progression in various organisms, including humans. The disclosure further provides a mouse comprising a mutant Ephrin pathway gene, such as Alk1, in brain endothelial cells only, and methods of screening for therapeutically useful modulators of Ephrin pathway gene expression or gene product activity useful in treating or ameliorating a symptom of arteriovenous malformation, such as Hereditary Hemorrhagic Telangiectasia or hemorrhagic stroke.

The present disclosure describes systems and methods for determining spatial accumulation of signaling molecules within tissue samples. Embodiments of the present disclosure are directed to integrating spatial and expression data for cells in a tissue. Embodiments further describe identifying cell linkages and rendering transcriptome profiles to spatial coordinates. Some embodiments further convolve diffusion information for various ligands and measure effective concentrations within cell areas. Using this information, embodiments are able to predict cell-cell signaling information.

Provided is a cell structure including: a connective tissue structure; and an epithelial structure placed on the connective tissue structure, in which the connective tissue structure contains a fragmented extracellular matrix component and first cells including mesenchymal cells, at least a part of the fragmented extracellular matrix component is placed between the first cells, and the epithelial structure contains epithelial cells.

Provided is a technology allowing for stable supply of brain microvascular endothelium-like cells. This coating agent for inducing differentiation of pluripotent stem cells into brain microvascular endothelium-like cells contains at least one component of a Laminin-221 fragment or an N-terminal Vitronectin.

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 present invention provides a method of constituting a tissue construct in vitro using a tissue without depending on scaffold materials. A method of integrating a biological tissue with a vascular system in vitro, comprising coculturing a biological tissue with vascular cells and mesenchymal cells. A biological tissue which has been integrated with a vascular system by the above-described method. A method of preparing a tissue or an organ, comprising transplanting the biological tissue described above into a non-human animal and differentiating the biological tissue into a tissue or an organ in which vascular networks have been constructed. A method of regeneration or function recovery of a tissue or an organ, comprising transplanting the biological tissue described above into a human or a non-human animal and differentiating the biological tissue into a tissue or an organ in which vascular networks have been constructed. A method of preparing a non-human chimeric animal, comprising transplanting the biological tissue described above into a non-human animal and differentiating the biological tissue into a tissue or organ in which vascular networks have been constructed. A method of evaluating a drug, comprising using at least one member selected from the group consisting of the biological tissue described above, the tissue or organ prepared by the method described above, and the non-human chimeric animal prepared by the method described above. A composition for regenerative medicine, comprising a biological tissue which has been integrated with a vascular system by the method described above.

The present invention provides for methods for identifying modulators of extracellular matrix (ECM) movement towards a site requiring deposition of ECM. Such modulators can be applied for use in a method for the modulation of ECM movement towards a site requiring deposition of ECM, e.g. a wound, thereby allowing treatment of a condition involving ECM deposition. Since the modulator may either be an inhibitor or promoter, either excessive or insufficient ECM deposition could be dealt with by the means and methods of the present invention.

A method of screening for a substance that acts on a cell mass includes producing a cell mass by three-dimensional culture of primary cancer cells using a tumor tissue, adding a test substance to the cell mass, and evaluating an action of the test substance on the cell mass. The cell mass is produced by culturing cells obtained from the tumor tissue in a medium containing a 5% v/v or less extracellular matrix on a substantially low-adhesive cell culture substrate and producing the cell mass of the primary cancer cells.

Co-crystals and pharmaceutically acceptable salts and methods for the preparation of the co-crystals and the pharmaceutically acceptable salts of 8-chloro-N-(4-(trifluoromethoxy)phenyl)quinolin-2-amine, pharmaceutical compositions including them as well as their use as medicines and more particularly for use in the prevention and/or treatment of inflammatory diseases, diseases caused by viruses and/or cancer or dysplasia.