In related-art methods of differentiating pluripotent stem cells into a desired cell type, there has not been established a differentiation induction method using human ES/iPS cells and being stable and highly efficient. A method of inducing differentiation into a desired cell type within a short period of time and with high efficiency by attenuating differentiation resistance of a pluripotent stem cell to generate a pluripotent stem cell that actively proceeds to a differentiated cell type has been found, and thus the present invention has been completed.

Provided herein are methods and systems for bio-printing of three-dimensional organs and organoids. Also provided herein are bio-printed three-dimensional organs and organoids for use in the generation and/or the assessment of immunological products and/or immune responses. Also provided herein are methods and system for bio-printing three-dimensional matrices.

This disclosure describes efficient methods for separating desired populations of cells, including Multilineage-Differentiating Stress-Enduring (MUSE) cells. Also described are the methods for isolating and enriching MUSE cells through a sorting, expanding, and re-sorting procedure. The enriched cells or cell populations can be used for treating cancer, repairing various tissues, and treating various degenerative or inherited diseases.

The present invention provides a means for suppressing formation and/or proliferation of undesired cells derived from stem cells in a cell population containing cells differentiated from stem cells. The nutrition composition according to the present invention is a nutrition composition for suppressing formation and/or proliferation of undesired cells derived from stem cells in a cell population containing cells differentiated from stem cells, the nutrition composition containing at least one essential amino acid selected from the group consisting of isoleucine, leucine, methionine, lysine, phenylalanine, tryptophan, threonine and histidine except valine, and optionally containing a non-essential amino acid(s).

A method for inducing non-hepatocytes into hepatocyte-like cells, wherein the non-hepatocytes are induced to express or overexpress hepatic fate conversion and maturation factors, cultured in somatic cell culture medium, hepatocyte expansion culture medium and 2C medium for a sufficient period of time to convert the non-hepatocyte cell into cells with hepatocyte-like properties, are provided. The iHeps induced according to the methods are also provided.

Provided herein are methods and systems for bio-printing of three-dimensional organs and organoids. Also provided herein are bio-printed three-dimensional organs and organoids for use in the generation and/or the assessment of immunological products and/or immune responses. Also provided herein are methods and system for bio-printing three-dimensional matrices.

Universal human induced pluripotent stem cells (universal hiPSCs) and a method of forming the same are provided in the disclosure, including the following steps: providing a first cell group including human stem cells; providing a second cell group including human mononuclear cells; in some embodiments, the second cell group further includes human stem cells, in which the human stem cells of the second cell group are allogenic cells from the first cell group; mixing the first cell group and the second cell group to form cell mixture; maintaining the cell mixture at a temperature below 30° C. for at least one day; reprogramming the human stem cells of the cell mixture to obtain universal hiPSCs. The universal hiPSCs includes human leukocyte antigen-1 (HLA class I) gene and human leukocyte antigen-2 (HLA class II) gene, but no HLA class I and HLA class II expressions.

Methods of tissue engineering, and more particularly methods and compositions for generating various vascularized 3D tissues, such as 3D vascularized embryoid bodies and organoids are described. Certain embodiments relate to a method of generating functional human tissue, the method comprising embedding an embryoid body or organoid in a tissue construct comprising a first vascular network and a second vascular network, each vascular network comprising one or more interconnected vascular channels; exposing the embryoid body or organoid to one or more biological agents, a biological agent gradient, a pressure, and/or an oxygen tension gradient, thereby inducing angiogenesis of capillary vessels to and/or from the embryoid body or organoid; and vascularizing the embryoid body or organoid, the capillary vessels connecting the first vascular network to the second vascular network, thereby creating a single vascular network and a perfusable tissue structure.

The invention provides compositions and methods of use in reprogramming somatic cells. Compositions and methods of the invention are of use, e.g., for generating or modulating (e.g., enhancing) generation of induced pluripotent stem cells by reprogramming somatic cells. The reprogrammed somatic cells are useful for a number of purposes, including treating or preventing a medical condition in an individual. The invention further provides methods for identifying an agent that reprograms somatic cells to a pluripotent state and/or enhances the speed and/or efficiency of reprogramming. Certain of the compositions and methods relate to modulating the Wnt pathway.

The present disclosure relates to a method for producing mesenchymal stem cells from pluripotent stem cells and mesenchymal stem cells prepared by the method. The present disclosure enables mesenchymal stem cells having superior proliferation rate while having superior intrinsic biological activity to be obtained with high yield by sequentially performing three-dimensional suspension culture using pluripotent stem cells, particularly induced pluripotent stem cells (iPSCs), as starting cells and adherent culture of cell aggregates formed therethrough. The mesenchymal stem cells produced by the method of the present disclosure can be usefully used in compositions for treating bone diseases, cartilage diseases or inflammatory and autoimmune diseases owing to high differentiation efficiency into bone and cartilage and superior anti-inflammatory activity.