Provided herein are methods that enable the polarization of hPSC mesoderm such that closely related yet distinct cardiovascular populations can be generated efficiently without the need of post-facto enrichment.

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 present invention relates to a population of cells with an increased proportion of left ventricular cardiomyocytes, and uses thereof, for example in treatment of disorders of the left ventricle and use in screening for drugs which may be used to treat disorders of the left ventricle.

The present invention relates to a method for preparing highly pure pancreatic progenitor cells by using pluripotent stem cells such as ES cells or iPS cells as a source, inducing their differentiation into pancreatic progenitor cells, and culturing and proliferating the pancreatic progenitor cells. Specifically, the present invention relates to a method for proliferation of pancreatic progenitor cells, comprising the step of culturing the pancreatic progenitor cells in a medium containing (i) an EGF signal transduction activator and/or an FGF signal transduction activator and (ii) a ROCK inhibitor.

The present invention relates to expandable liver organoids, a medium composition for differentiation thereof, and a method for producing liver organoids using the same, and the liver organoids according to the present invention exhibit the characteristics of more mature hepatocytes than 2D differentiated hepatocytes, can be subcultured up to 90 times or more, and exhibit the expandability for maintaining the characteristics of mature hepatocytes even after multiple subcultures, and thus can be usefully utilized for predicting toxicity, regeneration, and inflammatory response, drug screening, and modeling of diseases such as hepatic steatosis.

The present invention relates to inter alia, methods for the generation and maintenance of Mesoderm-derived ISL1+ Multipotent Progenitors (IMPs), the production of a number of pluripotent cells including and epicardial pluripotent cells (EPCs) and using these cells to produce endothelial cells, cardiomyocytes, smooth muscle cells, vascular cells and other cells and related methods as otherwise disclosed herein. The invention also relates to compositions comprising a population of cells.

The present invention describes an efficient and rapid protocol to generate hepatocyte cells from human induced pluripotent stem cells (iPSCs). According to the method, the iPS cells can be differentiated into functional hepatocyte cells in a short time course (less than 15-20 days). The iPSC-derived hepatocyte cells of the invention have a similar gene expression profile to mature hepatocytes. Moreover, the iPSC-derived hepatocyte cells is proved to rescue lethal fulminant hepatic failure in a non-obese diabetic severe combined immunodeficient mouse model. The rapid and efficient differentiation protocol for generation of iPSC-derived hepatocyte cells may offer an alternative option for treatment of liver diseases.

An object is to prepare an intestinal organoid having a characteristic close to the small intestine of a living body, from a pluripotent stem cell. An intestinal organoid is prepared from a pluripotent stem cell, by the following steps of: (1) differentiating the pluripotent stem cell into an endoderm-like cell; (2) differentiating the endoderm-like cell obtained in step (1) into an intestinal stem cell-like cell; (3) culturing the intestinal stem cell-like cell obtained in step (2) in the presence of an epidermal growth factor, a fibroblast growth factor, a TGF β receptor inhibitor, a GSK-3 β inhibitor, and a ROCK inhibitor; (4) culturing the cell obtained in step (3) to form a spheroid; and (5) differentiating the spheroid formed in step (4) to form an intestinal organoid, wherein the differentiation includes culturing in the presence of an epidermal growth factor, a BMP inhibitor, and a Wnt signal activator. Also, a plane culture system is prepared by subjecting the cells constituting the intestinal organoid formed in step (5) to plane culture in the presence of an epidermal growth factor and a TGF β receptor inhibitor. A highly functional evaluation system having the villi structure is constructed by using air-liquid interface culture in the plane culture.

Methods and composition for the production of cardiomyocytes from differentiation of pluripotent stem cells are provided. For example, in certain aspects methods including differentiating pluripotent stem cells in a large volume of suspension culture in the presence of ROCK inhibitors are described. In further aspects, methods for differentiation of stem cells into cardiomyocytes that overcome variability between different stem cell clones and different batch of culture medium are provided.

The present invention provides methods to promote the differentiation of pluripotent stem cells. In particular, the present invention provides an improved method for the formation of pancreatic endoderm, pancreatic hormone expressing cells and pancreatic hormone secreting cells. The present invention also provides methods to promote the differentiation of pluripotent stem cells without the use of a feeder cell layer.