The invention relates to improved culture methods for expanding epithelial stem cells and obtaining organoids, to culture media involved in said methods, and to uses of said organoids.

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 TGF 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.

The invention relates to improved culture methods for expanding epithelial stem cells and obtaining organoids, to culture media involved in said methods, and to uses of said organoids.

The present invention provides a method for producing a retinal progenitor cell, including (1) a first step of subjecting pluripotent stem cells to floating culture in a serum-free medium to form an aggregate of pluripotent stem cells, and (2) a second step of subjecting the aggregate formed in step (1) to floating culture in a serum-free medium or serum-containing medium each being free of a substance acting on the Sonic hedgehog signal transduction pathway but containing a substance acting on the BMP signal transduction pathway, thereby obtaining an aggregate containing retinal progenitor cells.

The present invention is drawn, in part, to biocompatible compositions comprising a biocompatible polymer matrix and conditioned cell medium comprising i) a cell culture medium and ii) one or more agents synthesized by and secreted from one or more cells cultured in the cell culture medium, as well as therapeutic uses thereof, particularly in modulating bone and/or gum tissue growth.

Provided is a method for producing chondrocytes from pluripotent stem cells, the method comprising the steps of: (i) culturing pluripotent stem cells under adherent conditions in a medium containing an HMG-CoA reductase inhibitor and one or more substances selected from the group consisting of BMP2, TGF and GDF5, and (ii) culturing the cells obtained in step (i) under suspension conditions in a medium containing an HMG-CoA reductase inhibitor and one or more substances selected from the group consisting of BMP2, TGF and GDF5. Also provided is a pharmaceutical product comprising chondrocytes obtained by the method.

The present invention relates to a method for producing pancreatic progenitor cells from pluripotent stem cells. More specifically, the present invention relates to a method for producing pancreatic progenitor cells, comprising causing the action of a factor having the inhibitory activity for cyclin-dependent kinase 8 and/or cyclin-dependent kinase 19 (hereinafter, also abbreviated to CDK8/19).

The present invention provides a method for producing a retinal progenitor cell, including (1) a first step of subjecting pluripotent stem cells to floating culture in a serum-free medium to form an aggregate of pluripotent stem cells, and (2) a second step of subjecting the aggregate formed in step (1) to floating culture in a serum-free medium or serum-containing medium each being free of a substance acting on the Sonic hedgehog signal transduction pathway but containing a substance acting on the BMP signal transduction pathway, thereby obtaining an aggregate containing retinal progenitor cells.

Cell populations of intestinal midgut endoderm cells and methods of generating the cells expressing markers characteristic of intestinal endoderm lineage are disclosed. Methods of treating conditions such as diabetes are also disclosed.

Provided herein are compositions and methods useful for the expansion of hematopoietic stem and progenitor cells, such as those that have been genetically modified, for instance, to express a heterologous transgene. In accordance with the composition and methods described herein, hematopoietic stem and progenitor cells may be genetically modified, for example, to express transgenes encoding therapeutic proteins. Genetically modified hematopoietic stem and progenitor cells may be expanded, for instance, by treatment ex vivo with an aryl hydrocarbon receptor antagonist, and may be infused into a patient, such as a patient in need of hematopoietic stem cell transplant therapy. Thus, provided herein are methods for the treatment of various stem cell disorders, including hematopoietic diseases, metabolic disorders, cancers, and autoimmune diseases, among others.