The invention is directed to in vitro methods of inducing differentiation of anterior foregut endoderm and the enriched populations of anterior foregut endoderm produced by such methods. Such enriched populations are useful for studies of the molecular events that occur during differentiation and for generating cells for cell replacement therapy.

The generation of complex organ tissues from human embryonic and pluripotent stem cells (PSCs) remains a major challenge for translational studies. It is shown that PSCs can be directed to differentiate into intestinal tissue in vitro by modulating the combinatorial activities of several signaling pathways in a step-wise fashion, effectively recapitulating in vivo fetal intestinal development. The resulting intestinal “organoids” were three-dimensional structures consisting of a polarized, columnar epithelium surrounded by mesenchyme that included a smooth muscle-like layer. The epithelium was patterned into crypt-like SOX9-positive proliferative zones and villus-like structures with all of the major functional cell types of the intestine. The culture system is used to demonstrate that expression of NEUROG3, a pro-endocrine transcription factor mutated in enteric anendocrinosis is sufficient to promote differentiation towards the enteroendocrine cell lineage. In conclusion, PSC-derived human intestinal tissue should allow for unprecedented studies of human intestinal development, homeostasis and disease.

Methods of generating functional human brown adipocytes, comprising exposing human stem cells, progenitor cells, or white adipocytes to culture with an differentiation cocktail that comprises one or more browning agents (e.g., one or more macromolecular crowders), and optionally one or more adipogenic agents, are described, as are populations of human brown adipocytes generated by the methods, and uses for the populations. Methods of generating functional human brown adipocytes in an individual, such as by administering a pharmaceutical composition comprising an differentiation cocktail, are also described.

There is provided herein cell culture mediums for generating organoids, including tumour organoids.

The invention provides a method for producing a ciliary marginal zone stem cell induced to differentiate from a pluripotent stem cell, including either the following step (1) or step (2), or both of these steps: (1) a step of floating culturing cells obtained from a cell aggregate containing a ciliary marginal zone-like structure induced to differentiate from pluripotent stem cells, thereby obtaining a retinosphere; and (2) a step of collecting stage specific embryonic antigen-1 positive cells from cells obtained from a cell aggregate containing a ciliary marginal zone-like structure induced to differentiate from pluripotent stem cells.

This document provides methods and materials relating to cardiac cells. For example, this document provides methods and materials that can be used to obtain cells having the ability to differentiate into cardiomyocytes. Such cells can be used to repair damaged heart tissue. For example, cells having the ability to differentiate into cardiomyocytes can be used to repair or regenerate heart tissue in patients with a cardiac condition (e.g., ischemic cardiomyopathy, myocardial infarction, or heart failure).

The present invention relates to methods for encapsulating pancreatic progenitors in a biocompatible semi-permeable encapsulating device. The present invention also relates to production of human insulin in a mammal in response to glucose stimulation.

Methods, kits, compositions, and systems are provided for culturing pluripotent stem cells to produce populations of cells comprising beta-like cells (e.g., pancreatic lineage, glucose-responsive, and/or insulin-producing). In particular, culture conditions are provided that result in the generation of beta-like cells from a starting culture of human pluripotent stem cells.

The invention provides pharmaceutical compositions comprising human immature dental pulp stem cells (hIDPSCs) wherein the hIDPSCs express CD44 and CD13. The invention also provides methods of treating a neurological disease or condition comprising systemically administering to a subject a pharmaceutical composition comprising hIDPSCs wherein the hIDPSCs express CD44 and CD13. For example, for treating neurological diseases or conditions including supporting the neuro-protective mechanism in subjects diagnosed with early HD or repairing lost DA neurons in subjects diagnosed with PD.

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.