A production method for an organoid, the production method including a step of culturing adult stem cells or a cell tissue piece including adult stem cells in a medium containing a chimeric Fibroblast Growth Factor (FGF) that includes a partial region of FGF1 and a partial region of FGF2; an organoid produced by the production method; a medium including a chimeric FGF and having a content of chimeric FGF of 50 ng/mL or less; and an evaluation method for a test substance are provided, and according to the chimeric FGF, a content of growth factors included in a medium can be reduced.

Disclosed herein are cell cultures comprising dorsal and/or ventral PDX1-positive foregut endoderm cells and methods of producing the same. Also disclosed herein are cell populations comprising substantially purified dorsal and/or ventral PDX1-positive foregut endoderm cells as well as methods for enriching, isolating and purifying dorsal and/or ventral PDX1-positive foregut endoderm cells from other cell types. Methods of identifying differentiation factors capable of promoting the differentiation of dorsal and/or ventral PDX1-positive foregut endoderm cells, are also disclosed.

The invention relates to improved methods for culturing an epithelial stem cell or an organoid comprising epithelial stem cells. The invention also relates to culture media suitable for use with said methods, organoids obtainable or obtained by said methods and uses of said culture methods, media and organoids in drug discovery and validation, toxicity assays, diagnostics and therapy.

The present disclosure relates, inter alia, to perturbagens and methods for directing a change in the cell state of an intestinal stem cell. It also relates to methods for increasing a quantity of enteroendocrine cells, goblet progenitors, goblet cells, and/or Paneth cells or immediate progenitors thereof and/or the ratios thereof. Further, the present disclosure relates to methods for treating diseases or disorders characterized by, at least, abnormal function, abnormal ratios and/or abnormal numbers of enteroendocrine cells, goblet progenitors, goblet cells, and/or Paneth cells, or immediate progenitors thereof.

The present disclosure addresses IBD from the standpoint of inhibiting or ablating pathogenic mucosal stem cells cloned from defined regions of disease in the gastrointestinal tract. In the case of Crohn's disease, for example, isolation of those stem cells according to the methods of the present disclosure reveals a pattern of inflammatory gene expression in stem cells from the terminal ileum and colon that is epigenetically maintained despite months of continuous cultivation in the absence of immune or stromal cells, or of intestinal microbes. Superimposed on this distributed inflammatory phenotype is a differentiation defect that profoundly and specifically alters the mucosal barrier properties of the terminal ileum. The co-existence of diseased and normal stem cells within the same endoscopic biopsies of Crohn's disease patients implicates an epigenetically enforced heterogeneity among mucosal stem cells in the dynamics of this condition.

The invention provides for methods of differentiating pancreatic endocrine cells into pancreatic beta cells expressing PDX1, NKX6.1, MAFA, UCN3 and SLC2A. These pancreatic beta cells may be obtained by step-wise differentiation of pluripotent stem cells. The pancreatic beta cells exhibit glucose-dependent mitochondrial respiration and glucose-stimulated insulin secretion similar to islet cells.

Provided herein are methods and compositions relating, in part, to the generation of human progenitor cells committed to the lung lineage and uses of such cells for treatment of lung diseases/disorders or injury to the lung. Whether an adult stem cell can be isolated from human adult lung remains controversial in the art and at present, methods for isolating and using adult lung stem cells from humans lack reproducibility. Thus, the methods and compositions described herein are advantageous over the present state of knowledge in the art and permit the generation of human lung progenitor cells for treatment, tissue engineering, and screening assays.

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.

A method of treating colorectal cancer included placing a high intensity focused ultrasound (HIFU) probe proximate a designated treatment volume at one of the colon and the rectum of a patient. The method further includes delivering HIFU via the HIFU probe at a frequency of at least 1 mHz for at least 3 seconds to raise a temperature of a first portion of the designated treatment volume to above 65° C., thereby ablating the first portion and causing a tissue defect within the designated treatment volume. The method further includes applying a nonablative dose of energy via the HIFU probe to a second portion of the designated treatment volume to provoke stem cell homing in the second portion, thereby encouraging tissue regrowth.

Disclosed herein are cell cultures comprising definitive endoderm cells and methods of producing the same. Also disclosed herein are cell populations comprising substantially purified definitive endoderm cells as well as methods for enriching, isolating and purifying definitive endoderm cells from other cell types.