Abstract: A cell culture container includes a storage container, a cell culture area, a culture solution supply unit, and a discharge unit. The cell culture area is a region for culturing cells, and is provided in the storage container. The culture solution supply unit supplies the culture solution into the cell culture area at a flow rate equal to or less than a predetermined flow rate. The discharge unit discharges the liquid in the cell culture area to the outside of the storage container. A rectification unit is a structure in which a plurality of outflow ports are uniformly arranged in a direction perpendicular to the flow direction of the culture solution from the culture solution supply unit to the discharge unit.

Abstract: The instant disclosure relates to compositions derived from precursor cells, and methods of using such compositions, for the manufacture of hematopoietic stem cells (HSCs) or derivative immune cells. More particularly, methods for obtaining hematopoietic stem cells from organoid tissue or cultures comprising organoids are disclosed, wherein the organoid tissue or cultures comprise liver or colonic tissue derived from precursor cells (such as embryonic stem cells or induced pluripotent stem cells), via directed differentiation.

Abstract: Disclosed herein are bioartificial liver systems (“BAL” or “liver assist device”) that employ liver organoids. The disclosed systems may be used to provide a therapeutic benefit to an individual in need thereof, particularly an individual having compromised liver function. The systems may include an in vivo or ex vivo component, wherein a liver function is provided to the individual using the disclosed systems.

Abstract: A tissue structure for enabling comprehensive understanding of gene patterns of mature cells and a method of preparing the tissue structure are provided. A tissue structure is obtained by co-culturing an endodermal, ectodermal, or mesodermal cell derived from a stem cell and at least one cell and/or factor selected from the group consisting of a vascular cell, a mesenchymal cell, a factor secreted by a vascular cell, a factor secreted by a mesenchymal cell, and a factor secreted when both a vascular cell and a mesenchymal cell exist. A value obtained by assay of a plurality of functions using a Pearson product-moment correlation coefficient is closer to a value of a cell or biological tissue sampled from an adult than a value of a cell or biological tissue sampled from a fetus.

Abstract: Disclosed herein are hepato-biliary-pancreatic organoid (“HBPO” or “HBP organoid”) compositions, and methods of making and using hepato-biliary-pancreatic organoid compositions. The disclosed compositions may have two or more functions selected from hepatic tissue function, biliary tissue function, exocrine pancreatic function, and endocrine pancreatic tissue function. Methods of treating individuals using the hepato-biliary-pancreatic organoid compositions is also disclosed.

Abstract: Disclosed are digitized organoids comprising a detectable sensor, such as, for example, a Radio frequency identification (RFID) based sensor. Further disclosed are methods for making the digitized organoids. The disclosed methods allow for self-assembly mediated incorporation of ultracompact RFID sensors into organoids. Methods of using the digitized organoids are also disclosed.

Abstract: Disclosed are methods of treating or reducing the occurrence of a steatohepatitis disorder. The disorder may include, for example, NASH, parenteral nutrition associated liver disease (PNALD), or genetic forms of liver disease. The method may comprise the step of administering a composition comprising obeticholic acid to an individual in need thereof.

Abstract: The present invention solves the following problems [1] to [3] found in conventional methods of preparing a three dimensional structure (organ primordium) by coculturing functional cells with umbilical cord-derived vascular endothelial cells and bone marrow-derived mesenchymal cells: [1] the quality of resultant organ primordia varies greatly depending on donors; [2] the growth capacities of cell sources are limited; and [3] it is difficult to secure immunocompatibility because cells are derived from different sources. An organ bud prepared from vascular cells, mesenchymal cells and tissue or organ cells, wherein each of the vascular cell, the mesenchymal cell and the tissue or organ cell has been induced from pluripotent stem cells. A method of preparing an organ bud, comprising culturing vascular cells, mesenchymal cells and tissue or organ cells in vitro, wherein each of the vascular cell, the mesenchymal cell and the tissue or organ cell has been induced from pluripotent stem cells.

Abstract: The present invention provides a culture method for culturing, in recesses (10), a population including two or more cells including a cell derived from a stem cell and a mesenchymal cell. The cell derived from a stem cell is a cell obtained by differentiating a stem cell in vitro. The cell is a cell of one or more types selected from the group consisting of an endodermal cell, an ectodermal cell, and a mesodermal cell. The population is cultured in the recesses (10) together with a vascular cell or a secretor factor. Each recess (10) includes a space in which cells are movable. When a volume of the space is represented by V mm3 and the number of mesenchymal cells seeded in the space is represented by N, V is 400 or less and N/V is in a range from 35 to 3000.

Abstract: Disclosed are methods of inducing formation of a liver organoid from precursor cells, such as iPSC cells. The disclosed liver organoids may be used for screening for a serious adverse event (SAE), such as liver failure and/or drug induced liver injury (DILI), and/or drug toxicity. The disclosed liver organoids may also be used to treat an individual having liver damage, or for identifying a preferred therapeutic agent.

Abstract: Disclosed are methods of treating or reducing the occurrence of a steatohepatitis disorder. The disorder may include, for example, NASH, parenteral nutrition associated liver disease (PNALD), or genetic forms of liver disease. The method may comprise the step of administering a composition comprising obeticholic acid to an individual in need thereof.

Abstract: An operation isolator forms an aseptic space. An incubator is connected to the operation isolator, in which cells are stored and cultured. A storage chamber stores articles used in the operation isolator. In order to carry articles from the outside into the storage chamber, a decontamination pass-box is provided. The storage chamber and the operation isolator are directly or indirectly connected to each other.

Abstract: Provided is a culture chamber that includes a plurality of recesses each formed of a bottom portion and an opening portion. The bottom portion has a hemispherical shape or a truncated cone shape. The opening portion is defined by a wall that surrounds an area from a boundary between the opening portion and the bottom portion to an end of each of the recesses, the wall having a taper angle in a range from 1 to 20 degrees. An equivalent diameter of the boundary is from 50 ?m to 2 mm and a depth from a bottom of the bottom portion to the end of each of the recesses is from 0.6 or more times to 3 or less times the equivalent diameter, and the wall defining the opening portion forms a surface continuous to the bottom portion. An inclination of the continuous surface changes at the boundary.

Abstract: Disclosed herein are methods of making and using lipotoxic organoid models. In certain aspects, the methods may comprise the steps of contacting a liver organoid with a free fatty acid (FFA) composition. In one aspect, the FFA composition may comprise oleic acid, linoleic acid, palmitic acid, or combinations thereof.

Abstract: 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.

Abstract: A culture chamber includes a plurality of recesses (10) each formed of a bottom portion (11) and an opening portion (12). The bottom portion (11) has a hemispherical shape and the opening portion (12) is defined by a wall that surrounds an area from a boundary between the opening portion (12) and the bottom portion (11) to an end of each of the recesses (10), the wall having a taper angle in a range from 1 degree to 20 degrees. An equivalent diameter of the boundary is in a range from 50 ?m to 2 mm and a depth from a bottom of the bottom portion (11) to the end of each of the recesses is in a range from 0.6 or more times to 3 or less times the equivalent diameter, and the wall defining the opening portion (12) forms a surface continuous to the bottom portion (11).

Abstract: Disclosed are methods of treating or reducing the occurrence of a steatohepatitis disorder. The disorder may include, for example, NASH, parenteral nutrition associated liver disease (PNALD), or genetic forms of liver disease. The method may comprise the step of administering a composition comprising obeticholic acid to an individual in need thereof.

Abstract: Disclosed are methods of inducing formation of a liver organoid from precursor cells, such as iPSC cells. The disclosed liver organoids may be used for screening for a serious adverse event (SAE), such as liver failure and/or drug induced liver injury (DILL), and/or drug toxicity. The disclosed liver organoids may also be used to treat an individual having liver damage, or for identifying a preferred therapeutic agent.

Abstract: A virus infection model which overcomes the drawbacks of conventional hepatitis virus infection models is provided. A method for constructing a virus infection model capable of recapitulating a viral life cycle, comprising infecting a cell condensate formed by culturing a tissue or organ cell in vitro with a virus. A virus infection model capable of recapitulating a viral life cycle, comprising a virus-infected cell condensate, wherein the cell condensate is formed by culturing a tissue or organ cell in vitro. A method of screening for substances with antiviral activity, comprising using the virus infection model.

Abstract: The present invention provides a technique that serves as a platform for inducing human organ cells at a low cost, stably and in a large quantity. A cell inducible after differentiating pluripotent stem cells and then passaging the resultant cells at least once or more times, which is negative for undifferentiated (pluripotent) cell markers NANOG, OCT4, MYC and LIN28A, negative for endoderm cell markers CXCR4, CER1, HHEX and GATA4, positive for intestinal endoderm cell markers CDX2 and HOXB9, negative for a mesenchymal cell marker brachyury (T), negative for a pancreatic cell marker PDX1, and capable of differentiating into at least a hepatocyte, a pancreatic cell and an intestinal cell. Also provided are methods of preparing and amplifying the above cells; a method of preparing organ cells using the above cells; and a method of constructing a working cell bank for preparing organ cells, comprising cryopreserving the above cells.