Provided are: a production device by which a cell structure having a three-dimensional structure is produced using a plurality of linear members; a production system therefor; and a production method therefor. The production device 100 comprises a top plate 110, pins 120A to 120D, a first slide plate 130, a second slide plate 140, a stopper 150, a base plate 160, an outer peripheral needle-shaped member 170 and an inner peripheral needle-shaped member 180. Cell aggregates 400 are put into a three-dimensional tubular space S1 that is defined by the outer peripheral needle-shaped member 170 and the inner peripheral needle-shaped member 180. Then, the top plate 110 is pressed downward on the accumulated cell aggregates 400. Thus, the cell aggregates 400 are immersed in a culture solution 210 and stuck together so that a tubular cell structure 500 is produced using the three-dimensional space S1 as a mold.

Provided herein are methods of producing a distinct bilayer culture of retinal epithelial cells (RPE) with photoreceptor cells and/or photoreceptor precursor cells (PR/PRP). Further provided herein is a therapy comprising transplantation of the RPE and PR/PRP bilayer as well as methods for testing candidate drugs using the bilayer.

The present specification provides a spontaneous-contracting cardiac organoid, a method for manufacturing the organoid, and a method for evaluating drug toxicity by using same, the cardiac organoid comprising: a chamber in which a fluid is stored; a first pipe connected to the chamber so that the fluid flows therethrough; a second pipe connected to the chamber so that the fluid is discharged therethrough; and a valve formed on the first pipe so as to spontaneously open/close an inflow pipe.

The present invention provides a culture method capable of maturing an organoid through long-term culture, and suitable for producing a conformational organ. The culture method of the present invention is a method for culturing an organoid and/or cells constituting an organ immobilized in a chamber with a culture fluid perfused, and the culture fluid is perfused in such a manner as to generate a turbulent flow in the chamber.

A method for generating a heart organoid is provided. The method includes forming a cellular aggregate of pluripotent stem cells, activating Wnt signaling in the cellular aggregate to cause the cellular aggregate to differentiate into a three-dimensional cardiac mesoderm, and inhibiting the Wnt signaling in the cardiac mesoderm to form the heart organoid. The heart organoid includes myocardial tissue, endocardial tissue defining at least one chamber, and epicardial tissue disposed on at least an outer surface of the myocardial tissue. The heart organoid beats. Heart organoids prepared in accordance with the method are also provided.

The present invention relates to 3D brain organoids, uses thereof, methods and culture medium for generating such organoids. An aspect of the invention provides brain organoids and methods of generating such organoids with bilaterally symmetric optic vesicles, containing both neuronal and non-neuronal cell types, and exhibiting functional circuitry. These organoids can be generated within short time intervals (e.g., 50 days) and therefore are useful for medical modelling and applications.

The present invention relates generally to a three-dimensional cell and tissue culture system for the female reproductive tract. In particular provided herein the system includes individual female reproductive cultures in a dynamic microfluidic setting or integrated using a microfluidic microphysiologic system. In some embodiments, the present invention provides ex-vivo female reproductive tract integration in a three dimensional (3D) microphysiologic system.

Disclosed are compositions, in particular, organoid compositions, derived from more than one donor cell. Further disclosed are methods of making compositions, for example, organoid compositions, that comprise a differentiated cell population derived from more than one donor cell. Donor cells may include, for example, a precursor cell such as an embryonic stem cell or other precursor cell. The disclosed methods use synchronization conditions to produce a synchronized pooled-precursor cell population, which may then be differentiated into an organoid composition. Methods of using the compositions are also disclosed.

The present invention relates to microfluidic fluidic systems and methods for the in vitro modeling diseases of the lung and small airway. In one embodiment, the invention relates to a system for testing responses of a microfluidic Small Airway-on-Chip infected with one or more infectious agents (e.g. respiratory viruses) as a model of respiratory disease exacerbation (e.g. asthma exacerbation). In one embodiment, this disease model on a microfluidic chip allows for a) the testing of anti-inflammatory and/or anti-viral compounds introduced into the system, as well as b) the monitoring of the participation, recruitment and/or movement of immune cells, including the transmigration of cells. In particular, this system provides, in one embodiment, an in-vitro platform for modeling severe asthma as “Severe Asthma-on-Chip.” In some embodiments, this invention provides a model of viral-induced asthma in humans for use in identifying potentially effective treatments.

The present invention relates to a novel bioreactor system for preparing an engineered three- dimensional biological tissue construct. The bioreactor system comprises a cultivation chamber that is designed to allow the formation, cultivation and the subsequent testing and/or stimulation of tissue constructs on one or more support elements with a minimum risk of microbial contamination or mechanical damage The invention furthermore relates to a method for preparing an engineered tissue construct using the novel bioreactor system. The invention also relates to the use of the bioreactor system for preparing engineered biological tissue constructs, preferably tissue constructs which are suitable for being used in clinical tissue replacement and reconstructive therapy, drug development, drug screening, toxicity testing, cosmetic studies, safety testing, developmental studies, disease modeling, or food purposes.