Abstract: The present invention provides a composition having a metabolism-improving action, which comprises a supernatant of brown adipocytes or a purified product thereof. The present invention also provides a method of preparing the supernatant without using a culture solution comprising a high concentration of glucose. The present invention also provides a method of producing brown adipocytes using pluripotent stem cells, which are useful for preparing the supernatant of brown adipocytes. The present invention has succeeded in obtaining a supernatant having a metabolism-improving action from brown adipocytes. It was also possible to obtain the supernatant without using a culture solution comprising a high concentration of glucose. The present invention has also succeeded in producing brown adipocytes from pluripotent stem cells using a feeder-free culture system without adding a cytokine cocktail or the like.

Abstract: The problem is to produce functional liver cells usable in testing the metabolism and toxicity of a drug, from pluripotent stem cells. The solution includes a method for producing highly functional liver cells using pluripotent stem cells, comprising, from pluripotent stem cells, acquiring primitive endoderm derived from the pluripotent stem cells by a process involving steps (A) and (B), from the primitive endoderm, acquiring liver precursor cells by a process involving step (C), and, from the liver precursor cells, acquiring the highly functional liver cells by a process involving step (D): (A) culturing under serum-free and feeder-free conditions; (B) culturing in the presence of albumin and at least one kind of cytokine; (C) culturing in the presence of SHH or an SHH agonist and at least one kind of cytokine; and (D) culturing and maturing in the presence of at least one kind of cytokine.

Abstract: Provided are a method of producing brown adipocytes from pluripotent stem cells, a method of producing cell aggregates as an intermediate product thereof, pluripotent stem cell-derived cell aggregates and pluripotent stem cell-derived brown adipocytes produced by these methods, and cell therapy using the pluripotent stem cell-derived brown adipocytes. In the method of producing brown adipocytes from pluripotent stem cells, cell aggregates are produced from pluripotent stem cells by a method including the step (A), and brown adipocytes are prepared from the cell aggregates by a method including the step (B). The step (A) is a step of producing cell aggregates by non-adhesive culture of pluripotent stem cells in serum-free environment in the presence of a hematopoietic cytokine, and the step (B) is a step of producing brown adipocytes by adhesion culture of the cell aggregates in the presence of a hematopoietic cytokine.

Abstract: Provided are a method of producing brown adipocytes from pluripotent stem cells, a method of producing cell aggregates as an intermediate product thereof, pluripotent stem cell-derived cell aggregates and pluripotent stem cell-derived brown adipocytes produced by these methods, and cell therapy using the pluripotent stem cell-derived brown adipocytes. In the method of producing brown adipocytes from pluripotent stem cells, cell aggregates are produced from pluripotent stem cells by a method including the step (A), and brown adipocytes are prepared from the cell aggregates by a method including the step (B). The step (A) is a step of producing cell aggregates by non-adhesive culture of pluripotent stem cells in serum-free environment in the presence of a hematopoietic cytokine, and the step (B) is a step of producing brown adipocytes by adhesion culture of the cell aggregates in the presence of a hematopoietic cytokine.