125results about "Tissue screening" patented technology

The present disclosure provides methods of making tissue-derived epithelial organoids. In particular, the present disclosure provides a tissue-derived epithelial organoid embedded in a hydrogel suspended in a culture medium. The present disclosure further provides methods of using such organoids.

This method for culturing a cancer organoid includes culturing the cancer organoid on a top surface or inside of a cell structure in a medium not including an extracellular matrix, and the cell structure includes cells constituting stroma, and has two or more cell layers laminated in a thickness direction. A method for screening a test substance includes culturing a cell structure including the cancer organoid obtained by the method for culturing a cancer organoid in a presence of the test substance, and evaluating an effect of the test substance on the cancer organoid.

The present disclosure relates to methods and compositions for generating topographically organized tissues in vitro, for the resulting cultured tissue and components thereof, and for uses of such cultured tissue and its components in drug discovery, toxicology studies, and therapy.

To provide an intestinal organoid equipped with the same function as an intestine, and a method for manufacturing the organoid.SOLUTION: An intestinal organoid of the present invention is derived from an embryonic stem cell and / or an artificial pluripotent stem cell, has a structure including a cavity, and a length in a long axis direction is 5 mm or more. A method for manufacturing an intestinal organoid of the present invention includes: a process 1 of inoculating a cell selected from an embryonic stem cell and an artificial pluripotent stem cell onto a substrate and a cell culture substrate including a cell adhesion region and a cell non-adhesion region surrounding the cell adhesion region which are formed on the surface of the substrate; and a process 2 of culturing a cell inoculated in the process 1. The process 2 includes differentiating a part of a cell into an entodermal cell and differentiating a part of a cell into an ectodermal cell.SELECTED DRAWING: Figure 1D

Provided are: an agent for organoid formation and proliferation in the absence of an extracellular matrix, the agent including a Hippo signaling pathway inhibitor as an active component; a method for organoid proliferation; an organoid proliferated by the above-described proliferation method; an agent for establishing an organoid in the absence of an extracellular matrix; a method for producing an organoid; an organoid produced by the above-described production method; a regenerative medicine preparation; and a method for screening for an agent that enables culture of an organoid in the absence of an extracellular matrix.

This method for producing a brain organoid including aggregated tau protein comprises: a step (a) for culturing pluripotent stem cells in the presence of SMAD inhibitor to form embryoid bodies; a step (b) for embedding the embryoid bodies in an extracellular matrix and three-dimensionally culturing the embryoid bodies in the presence of SMAD inhibitor and GSK3β inhibitor to form an organoid that includes neural precursor cells; a step (c) for removing the organoid from the extracellular matrix and suspension-culturing the organoid in the presence of LIF to form a brain organoid; a step (d) for forcing the brain organoid to express a modified MAPT gene; and a step (e) for further suspension-culturing the brain organoid after step (d) to obtain a brain organoid having an aggregated tau protein.

What is provided is a nervous system cell-containing spheroid having suitable drug responsiveness. There are provided a nervous system cell-containing spheroid including at least one kind of nerve cells and nervous system cells other than the nerve cells, in which the proportion of the volume of one cell layer positioned at an outer edge of the spheroid to the volume of the entire spheroid is 15% to 30%; a method for producing the nervous system cell-containing spheroid; and a method for evaluating a test substance, the method including a step of incubating a nervous system cell-containing spheroid in the presence of a test substance, and a step of evaluating an effect of the test substance on the nervous system cell-containing spheroid, in which the nervous system cell-containing spheroid includes at least one kind of nerve cells and nervous system cells other than the nerve cells, and the proportion of the volume of one cell layer positioned at an outer edge of the spheroid to the volume of the entire spheroid is 15% to 30%.

To provide, 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.SOLUTION: 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.SELECTED DRAWING: None

The field of the invention is in vitro assays for the production of in vitro organ culture systems and the use of such in vitro organ culture systems for screening assays in drug screening, patient selection and personalized medical context. More specifically, the present invention relates to an in vitro method of establishing a tumor organoid from a cancer tissue sample obtained from a subject, an in vitro method of providing immune cells activated by an autologous tumor organoid, a method of preparing an in vitro organ culture system for mimicking interaction of a tumor with an immune system of a subject, and a method of preparing an in vitro organ culture system for mimicking interaction of a tumor with an immune system of a subject. The invention relates to an in vitro organ culture system, and to an in vitro organ culture system produced thereby, to a method for determining the reactivity of a tumor to at least one immunooncology drug therapy using said in vitro organ culture system, and to a kit for preparing an in vitro organ culture system that mimics the interaction of a tumor with the immune system of a subject, as disclosed herein.

And a means for further improving the evaluation precision is provided in the aspect of evaluating pharmacokinetics / toxicity and efficacy by using the cell aggregate of a plurality of samples. A plate having a plurality of holes in which a liquid and an aggregate of kidney cells are accommodated, the openings of the holes being covered with a film, and the ratio of the total volume of the aggregate and the liquid relative to the total volume of the holes being a predetermined ratio.

The present invention relates to an intestinal epithelium model faithfully reproducing the pathophysiological mechanisms observed in vivo in the context of an inflammatory state of the intestinal barrier. The model according to the present invention comprises two compartments separated by a semi-permeable membrane. The first compartment, corresponding to the apical pole of the intestinal epithelium, comprises a coculture of Caco-2 cells differentiated into enterocytes and HT29-MTX cells differentiated into goblet cells. The second compartment, corresponding to the basolateral pole of the intestinal epithelium, comprises a culture of THP-1 monocytic cells differentiated into macrophages.The model according to the present invention is characterized in that the cells contained in the first compartment produce interleukin (IL-6) at a concentration greater than 100 pg / mL, and interleukin 8 (IL-8) at a concentration greater than 150 pg / mL, and the cells contained in the second compartment produce tumor necrosis factor α (TNF-α) at ​​a concentration greater than 40 pg / mL and interleukin 1β (IL-1β) at a concentration greater than 90 pg / mL. The present invention also relates to the method for obtaining this model as well as to a method for selecting candidate compounds for the treatment of inflammatory bowel diseases by verifying their ability to stop inflammation upon increase in permeability or to verify the restoration of permeability and the mucus layer.

This invention relates to the field of microfluidic chip technology, specifically to a dynamic microfluidic chip device, its preparation method, and its applications for studying CAR-T therapy for gliomas. The preparation method includes: fabrication of the microfluidic chip; reconstruction of neural tissue; reconstruction of the blood-brain barrier; and simulation of the glioma microenvironment. The dynamic microfluidic chip device includes a microfluidic chip; the microfluidic chip includes, from left to right, a vascular channel, a brain parenchyma channel, a tumor channel, and a subarachnoid channel; each of the vascular channel, brain parenchyma channel, tumor channel, and subarachnoid channel includes a cell culture chamber with an inlet on one side; the cell culture chambers of the vascular channel and the subarachnoid channel have corresponding outlets on the other side. The applications include: CAR-T cell infusion; observation of transmembrane migration; and detection of biomarkers. This invention, through the dynamic microfluidic chip device, its preparation method, and its applications, aims to achieve more accurate in vitro evaluation of CAR-T cell therapy.

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.

The present disclosure is directed to methods of producing a predictive model or human avatars for assessing Central Nervous System (CNS) disorders using organoids, optionally with artificial intelligence (Al).

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 Ω / cm2. 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.

The present invention relates to a three-dimensional organotypic skin model of hydrogel comprising: - an epidermis of human keratinocytes; - a dermis of human fibroblasts; and - immune cells derived from human induced pluripotent stem cells.

The present invention relates to purified biocompatible mucus capable of forming a gel. The mucus of the present invention may be provided in a tissue model along with a cell population. The mucin or tissue model of the present invention may be useful in in vitro models of digestion, mucus penetration, and / or epithelial transport.

An endometrium model including: a gel that includes a stroma system extracellular matrix; and endometrial epithelial cells, wherein at least a portion of the endometrial epithelial cells are exposed at the surface of the gel, and at least a portion of the endometrial epithelial cells that are exposed at the surface of the gel form a lumen structure and a non-lumen structure in a continuous manner. Additionally, a method for producing said endometrium model. Additionally, an endometrial implantation model including said endometrium model and embryo cells.

It is provided a protocol to induce the formation of lower respiratory tract organoids in only 21 days, the organoids containing markers of both proximal and distal regions. The organoids is obtained by leveraging cellular interactions between airway bronchial epithelial cells and fibroblasts. It is also provided the use of the organoids to study respiratory viral infections with strong similarity to adult lung tissue.

To provide methods for producing an artificial skeletal muscle tissue from pluripotent stem cells.SOLUTION: The present invention describes a method for preparing an engineered skeletal muscle tissue, as well as skeletal myoblasts, skeletal myotubes, and satellite cells, a medium used being serum-free and different chemicals and their concentrations, as well as the physical stimuli, being defined. Additionally, the methods described herein are performed without transfection of human cells with transgenes. The engineered skeletal muscle cells exhibit myoblast-, myotube-, or satellite cell-specific genetic markers, demonstrating efficient differentiation of these cell types. Despite its engineered production, the skeletal muscle tissue possesses excellent stimulus-dependent contractility and exhibits contractions in response to different stimulation frequencies.SELECTED DRAWING: None

Organ-on-chip system, including a bio-engineered lung region that is functionally connected to a bio-engineered lymphatic region via a functionalized connection region. The bio-engineered lung region includes cultured or transplanted lung cells / tissue, which can mimic in vivo lung function, and the bio-engineered lymphatic region includes lymphatic cells / tissue, which can mimic in vivo lymphatic function. The connection region allows for stimuli and cell secretions to be transported between the lung region and the lymphatic region to confer immune competency to the lung region, as the lymphatic region can generate an immune response based on stimuli received from the lung region, for example, in response to infections or therapeutic agents

The present invention provides methods for engrafting a bone marrow organoid with CD34+ hematopoietic stem and progenitor cells. Compositions comprising the factors needed for engraftment are also provided.

The present invention provides a drug toxicity evaluation platform (evaluation method and kit therefor, etc.) that makes it possible to perform a detailed analysis of the likelihood that a drug will cause injury (DILI, etc.) to the liver or another organ. This method for evaluating drug toxicity includes a step for adding a drug to a co-culture of an organoid and blood cells, and a step for evaluating the toxicity of said drug to said organoid.

An anticancer drug assessment method including the steps of: culturing a cell structure containing stromal cells in which a gene encoding a live cell marker protein has been knocked out and cancer cells in the presence of an anticancer drug; and assessing the anticancer drug using an expression level of the live cell marker protein as an index in this order, wherein in the assessment, the expression level of the live cell marker protein is measured using a culture supernatant, or in the assessment, a substance that fluoresces or produces color when reacted with the live cell marker protein is added, and the expression level of the live cell marker protein is measured based on the amount of fluorescence or coloration of the substance.

Three-dimensional tumor avatars comprising an artificial scaffold, tumor cells, tumor associated endothelial cells and tumor associated fibroblast cells are provided. Kits comprising the 3D tumor avatars, methods of producing the 3D tumor avatars and methods of using the 3D tumor avatars are also provided.

The invention relates to a skin injury organ model and a method for screening drugs by using the skin injury organ model, and the skin injury organ model is characterized in that skin cells, accessory structures, nerve cells, fat cells and the like form structures similar to actual skin by using an air-liquid interface skin organ preparation technology; and the damaged skin is prepared by irradiating the skin-like organ with ultraviolet rays which actually reach the ground surface. In the present invention, the skin barrier is damaged and the activity of a matrix proteolytic enzyme is improved to promote the decomposition of collagen while increasing the secretion of pro-inflammatory cytokines by irradiating with solar-simulated ultraviolet light comprising 94.5% ultraviolet light (UV-A) and 5.5% ultraviolet light (UV-B), thereby well simulating the characteristics of skin injury caused by ultraviolet light. Therefore, the invention can be used as a model of skin injury and photoaging caused by ultraviolet rays, and can be useful in potential therapeutic drug screening.

We provide a treatment for atopic dermatitis. [Solution] A use is provided for manufacturing a pharmaceutical composition for the prevention or treatment of atopic dermatitis, comprising Cutibacterium acnes or its culture medium as an active ingredient.

This application describes methods for producing artificial skeletal muscle tissue from pluripotent stem cells. Methods for producing skeletal myoblasts, skeletal myotubes, and satellite cells from pluripotent stem cells are also disclosed. In the described methods, differentiation and maturation of pluripotent stem cells are directed toward skeletal myotubes and satellite cells. This application also describes artificial skeletal muscle tissue having multinucleated skeletal muscle fibers with satellite cells. Furthermore, the present invention relates to mesodermally differentiated skeletal myoblast progenitor cells, myogenically specialized skeletal myoblast progenitor cells, skeletal myoblasts, satellite cells, and skeletal myotubes that can be produced by means of the disclosed methods. This application also describes the use of skeletal muscle tissue or the disclosed cells in drug testing or medicine. Finally, this application relates to in vitro methods in which skeletal muscle tissue or the disclosed cells are used.

Disclosed herein are 3D printed vascular tissues and compositions and methods for making the 3D printed vascular tissues. The 3D printed vascular tissues can be used to model vascular tissue damage (e.g., vascular leakage) and in screening assays for agents that cause or inhibit or treat vascular tissue damage.

The invention relates to a method of generating endolymph-producing epithelial cells and in vitro use of a hedgehog signalling inhibitor for differentiation of inner ear progenitor cells into endolymph-producing epithelial cells; in vitro endolymph-producing epithelial cells and an inner ear organoid comprising endolymph-producing epithelial cells. Also provided is in vitro use of an inner ear organoid in drug discovery; the endolymph-roducing epithelial cells for use in a method of treating diseases of the inner ear; and a method of testing one of more therapeutic agents using these cells or organoids. Lastly, also provided is a kit and an organoid maturation medium.