Abstract: Disclosed herein are improved methods of maturing pluripotent stem cell-derived liver organoids with the use of hemoglobin metabolites such as bilirubin. Furthermore, by modulating the amounts of bilirubin used, liver organoids can be used as a model for hyperbilirubinemia. The scalability and tractability of these liver organoids made them excellent targets for drug screening against diseases such as hyperbilirubinemia. Also shown herein is the use of exogenous L-gulonolactone oxidase for improving viability of bilirubin-treated liver organoids.

Abstract: The present disclosure relates to construction of three-dimensional organs from pluripotent stem cells. The present disclosure also relates to a method of forming a cell condensate for self-organization.

Abstract: The present disclosure relates to an organ bud and a method of preparing an organ bud.

Abstract: The present invention provides a means for reconstituting tissues and organs having mature functions.

Abstract: An object of the present invention is to provide an ever-better method for producing sinusoidal endothelial cells. The present invention provides a method for producing sinusoidal endothelial cells from sinusoidal endothelial progenitor cells, the method comprising the step of culturing the sinusoidal endothelial progenitor cells in a medium containing one or more substances selected from the interleukin 6 (IL-6) family, for example, oncostatin M (OSM), interleukin 6 (IL-6), or interleukin 11 (IL-11).

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 the following method as an approach for enriching desired cells, particularly, yolk sac mesoderm cells or amniotic ectoderm cells, contained in an embryogenesis region-specific micropattern structure of a cell cluster formed by differentiation-inducing factors from a colony of pluripotent stem cells such as iPS cells: a method for producing a cell cluster enriched in desired cells from pluripotent stem cells, comprising the step of two-dimensionally culturing the pluripotent stem cells under Wnt signal regulation.

Abstract: The present invention provides drug toxicity evaluation platforms (such as an evaluation method and a kit therefor) that enable detailed analysis of the possibility and the like of developing drug-induced damage (such as DILI) to the liver and other organs. The method for evaluating drug toxicity of the present invention includes: a step of adding a drug to a co-culture system of an organoid and blood cells; and a step of evaluating the toxicity of the drug to the organoid.

Abstract: Provided is a culture chamber capable of preparing spheroids with a uniform size with high efficiency and having a micro-space structure which is designed to facilitate replacement of a medium and harvesting of cells. The 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 one of a hemispherical shape and a truncated cone 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.

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: The present invention provides means for producing a parathyroid gland organoid. A culture method of the present invention includes a cell population containing a parathyroid gland cell in a ratio of 50% or more, and a mesenchymal cell in a ratio of 10% or more; and a step of culturing the cell population.

Abstract: Disclosed herein are insulin resistance reporters for use in quantifying insulin response in biological cells. These biological cells may be stem cell compositions or derivatives thereof comprising the insulin resistance reporter. The stem cell derivatives include but are not limited to insulin responsive cells, tissues, or organoids, such as pancreatic, brain, adipose, muscle, or liver cells, or tissues or organoids thereof. Also disclosed herein are methods of using said insulin resistance reporters and cells with these insulin resistance reporters as models to examine insulin resistance and screening for compounds that are potentially useful for the treatment of diseases or disorders associated with insulin resistance. The cells comprising an insulin resistance reporter may be hepatic cells or liver organoid compositions, which can be used in investigating hepatic insulin resistance, for example, as a result of non-alcoholic fatty liver disease or steatohepatitis.

Abstract: 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.

Abstract: A pharmaceutical composition may be used in administering oxygen to a subject. The pharmaceutical composition may contain a perfluorocarbon dissolving oxygen therein. Further, a pharmaceutical composition may be used in decreasing the blood carbon dioxide partial pressure of a subject, and the pharmaceutical composition may contain a perfluorocarbon. Such a composition may be suitable for administered oral administration, nasogastric administration, trans-fistula gastric administration, or administration into a large intestine.

Abstract: A cell evaluation method includes acquiring a first evaluation index and a first index calculated using the first evaluation index with respect to comparative target cells in a culture process including a cell differentiation-inducing process in which cell differentiation is induced, calculating a second index on the basis of the first evaluation index with respect to evaluation target cells different from the comparative target cells, and evaluating differentiation of the evaluation target cells by comparing the first index with the second index.

Abstract: 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.

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: A method for screening for a therapeutic drug for a disease involving excessive activation of a complement, using a s cytotoxicity marker associated with the complement as an index, including (1a) a step of adding a complement to a cell produced from a stem cell to cause the cell to form a cytotoxicity marker associated with the complement, and (2a) a step of adding a therapeutic drug candidate, and selecting a substance that decreases the amount of the cytotoxicity marker is provided by the present invention.

Abstract: Existing single cell analysis techniques are generally high-resolution but are limited in the number of possible different experimental conditions. Disclosed herein are compositions and methods for multiplexed barcoding of a heterogenous population of cells using cationic polymers for delivery of nucleic acid barcodes to a cell population.

Abstract: Production and maintenance of hematopoietic stem cells in in vitro culture systems has proven to be elusive. Disclosed herein are hematopoietic stem cell compositions that originate from organoids such as liver organoids. These organoids also comprise a rare type of immune cell that is not yet fully elucidated due to the difficulty in isolating said immune cell from biological samples. Also disclosed herein are methods of producing said hematopoietic stem cells and immune cells from organoids, as well as methods of expanding hematopoietic stem cells from other sources using these organoids.