A composition having cell-derived physiological activity is provided. The composition according to the present invention contains a treated product of megakaryocytes or a culture of the megakaryocytes.

Methods of culturing embryonic stem cells, induced pluripotent stem cells and/or differentiated cells in culture medium comprising activin are described. In one aspect, the disclosure features a pluripotent human stem cell, wherein the stem cell comprises: (i) a genomic edit that results in loss of function of Cytokine Inducible SH2 Containing Protein (CISH) and (ii) a genomic edit that results in a loss of function of an agonist of the TGF beta signaling pathway, or a genomic edit that results in a loss of function of adenosine Ata receptor.

The present invention relates to a method of patterning and chopping 3D organoids prepared from human pluripotent stem cells, culturing the stem cells or progenitor cells, and inducing the differentiation thereof to obtain a large amount of finally differentiated cells. Compared to cells differentiated by a conventional differentiation method, the cells obtained in a large amount exhibit remarkably superior effects in terms of reproducibility, stability, and functionality, and thus are expected to be very useful for cell therapeutic agents or for the screening of therapeutic drugs.

The present disclosure provides compositions and methods for cell transplantation therapy based on forced expression of an exogenous HLA-F protein in donor cells to be transplanted into a subject. In some embodiments, the donor cells express an exogenous chimeric HLA-F protein comprising an extracellular region comprising an HLA-F alpha 1 domain, an HLA alpha 2 domain, an HLA-F alpha 3 domain, a linker and a β2m protein.

A method for producing CD4/CD8 double-positive T cells, comprising the steps of: (1) culturing pluripotent stem cells in a medium to induce hematopoietic progenitor cells; and (2) culturing the hematopoietic progenitor cells obtained in the step (1) in a medium containing a p38 inhibitor and/or SDF-1 to induce CD4/CD8 double-positive T cells.

Genetically modified cells that are compatible with multiple subjects, e.g., universal donor cells, and methods of generating said genetic modified cells are provided herein. The universal donor cells comprise at least one genetic modification within or near a gene that encodes one or more MHC-I or MHC-II human leukocyte antigens or a component or a transcriptional regulator of a MHC-I or MHC-II complex, wherein genetic modification comprises an insertion of a polynucleotide encoding a tolerogenic factor and/or survival factor. The universal donor cells may further comprise at least one genetic modification within or near a gene that encodes a survival factor, wherein said genetic modification comprises an insertion of a polynucleotide encoding a second tolerogenic factor and/or a different survival factor.

The present invention relates to a process for producing a population of cells which comprises mature atrial cardiomyocytes. The process comprises the step of treating iPS cells according to a treatment regimen which comprises contacting the iPS cells with Gremlin2 and retinoic acid, such that at least a portion of the iPS cells differentiate into mature atrial cardiomyocytes.

The disclosure provides a method for producing hepatocytes or hepatic progenitor cells; a method for suppressing hepatocyte aging using a drug causing histone hyperacetylation; a hepatocyte anti-aging agent; a method for increasing hepatocyte plasticity; and a drug for increasing hepatocyte plasticity.

In the various aspects and embodiments, this disclosure provides genetic, pharmacological, and mechanical stimuli for transitioning endothelial cells to hemogenic endothelial (HE) cells, and for transitioning HE cells to HSCs, including HSCs that comprise a significant level of LT-HSCs. The disclosure further provides methods for expanding HSCs using the genetic, pharmacological, and mechanical stimuli.

Compositions and methods are provided for production of cells useful in regenerative therapies.