The invention relates to a liver organoid, uses thereof and method for obtaining them.

The present invention provides a method for producing a human cell aggregate containing a midbrain-hindbrain boundary neural progenitor tissue, including subjecting an aggregate of human pluripotent stem cells to suspension culturing in a serum-free medium containing insulin, and treating, in the suspension culturing, the aggregate of human pluripotent stem cells or a human cell aggregate derived therefrom with a ROCK inhibitor, a TGFβ signal inhibitor, and a first fibroblast growth factor. Furthermore, the human cell aggregate containing the midbrain-hindbrain boundary neural progenitor tissue is subjected to suspension culturing in a serum-free medium to induce formation of a neuroepithelial structure by neural progenitor in the neural progenitor tissue, whereby the human cell aggregate containing the cerebellar plate tissue can be obtained.

Provided herein are methods of making and using a number of different types of liver cells.

Provided herein are methods of producing β cells and precursors thereof utilizing a Wnt signaling inhibitor or PKC activator, or both. Also provided herein are in vitro cultures comprising said cells, methods of treating a subject with a disease characterized by high blood sugar levels over a prolonged period of time by administering said cells, and devices for encapsulating said cells.

This application relates to non-human primate (NHP) induced pluripotent stem cell (IPSC)-derived hepatocytes, for example, Cynomolgus monkey (Macaca fascicularis) induced pluripotent stem cell-derived hepatocytes, and methods of producing the same. Moreover, this application relates to methods of using NHP IPSC-derived hepatocytes for drug screening, drug safety assessment and in models of infection.

The present invention relates to a method for fabrication of a three-dimensional lung organoid comprising human stem cell-derived alveolar macrophages. Specifically, a lung organoid is fabricated by co-culturing cells not expressing the definitive endoderm marker CRCX4 according to a fabrication method of the present disclosure. The lung organoid comprises type 1 and type 2 alveolar epithelial cells as well as alveolar macrophages and realizes infectious or inflammatory responses unlike conventional lung organoids that contain no immune cells and as such, can be advantageously used in studying mechanisms of related lung diseases, excavating biomarkers, developing therapeutic agents, and so on.

The present invention provides a method of producing more mature telencephalon or a progenitor tissue thereof, in vitro, from mammalian pluripotent stem cells, comprising obtaining a telencephalon marker-positive aggregate by culturing an aggregate of pluripotent stem cells in suspension in the presence of a Wnt signal inhibitor and a TGFβ signal inhibitor, and further culturing the telencephalon marker-positive aggregate in suspension under a high oxygen partial pressure condition. In one embodiment, the suspension culture under a high oxygen partial pressure condition is performed in the presence of a Wnt signal enhancer and a bone morphogenetic factor signal transduction pathway activating substance.

To provide means for efficient growth of epithelial cells capable of being used to manufacture regenerated hair follicle germs. Provided are a culture medium for growth of epithelial cells capable of being used to manufacture regenerated hair follicle germs, the culture medium comprising basal medium and at least (1) through (3), below: and a method for growing the epithelial cells using the culture medium: (1) at least one species of BMP inhibitor: (2) at least one species of fibroblast growth factor: and (3) at least one species of sonic hedgehog (SHH) and/or SHH agonist.

A method is provided for simultaneously producing both nephron progenitor cells and ureteric epithelial progenitor cells including the step of contacting intermediate mesoderm cells with: fibroblast growth factor 9 and/or fibroblast growth factor 20 and optionally, one or more selected from the group consisting of: bone morphogenic protein 7; heparin; a Wnt agonist; retinoic acid; and an RA antagonist. The concentrations of Wnt agonist, retinoic acid and/or RA antagonist may be manipulated to favour the relative production of nephron progenitor cells and ureteric epithelial progenitor cells. The intermediate mesoderm cells are ultimately derived from human pluripotent stem cells via a posterior primitive streak stage. The nephron progenitor cells and ureteric epithelial progenitor cells may have end uses such as for kidney repair and regeneration, bioprinting of kidneys and screening compounds for nephrotoxicity.

Described herein are methods, compositions, and kits for directed differentiation of human pluripotent stem cells into caudal lateral epiblasts, posterior neuroectoderm or posterior neuroepithelium, or motor neurons having specified HOX gene expression pattern mirroring a desired position along the rostral-caudal axis during hindbrain and spinal cord development. Also described are isolated populations of cells including caudal lateral epiblasts, posterior neuroectoderm, posterior neuroepithelium, or motor neurons having a HOX gene expression pattern specified to correspond to the HOX gene expression pattern associated with a desired rostral-caudal axis position.