Provided is an isolated population of human pluripotent stem cells comprising at least 50% human pluripotent stem cells characterized by an OCT4+/TRA1-60?/TRA1-81?/SSEA1+/SSEA4? expression signature, and novel methods of generating and maintaining same in a pluripotent, undifferentiated state a suspension culture devoid of cell clumps. Also provided are novel culture media, cell cultures and methods for culturing pluripotent stem cells in a suspension culture or a two-dimensional culture system while maintaining the cells in a proliferative, pluripotent and undifferentiated state. The novel culture media comprise interleukin 11 (IL11) and Ciliay Neurotrophic Factor (CNTF); bFGF at a concentration of at least 50 ng/ml and an IL6RIL6 chimera; or an animal contaminant-free serum replacement and an IL6RIL6 chimera. Also provided are methods for generating lineage-specific cells from the pluripotent stem cells.

It is an object of the present invention to provide a method for efficiently directing differentiation into insulin-producing cells in a xeno-free culture system. According to the present invention, there is provided a method for directed differentiation into insulin-producing cells, comprising culturing stem cells in the following steps (1) to (5): (1) a step of culturing stem cells in a medium comprising an activator of activin receptor-like kinase-4/-7 and a GSK3 inhibitor and then culturing in a medium comprising an activator of activin receptor-like kinase-4/-7; (2) a step of culturing the cells obtained in step (1) in a medium comprising a hedgehog signaling inhibitor and an FGF; (3) a step of culturing the cells obtained in step (2) in a medium comprising a retinoic acid receptor agonist, a hedgehog signaling inhibitor and a BMP signaling inhibitor; (4) a step of culturing the cells obtained in step (3) in a medium comprising a TGF- type I activin receptor-like kinase-4/-5/-7 inhibitor and a BMP signaling inhibitor; and (5) a step of culturing the cells obtained in step (4) in a medium comprising a phosphodiesterase inhibitor.

Methods are disclosed for reprogramming a somatic cell, including an adherent cell and a cell in suspension, into an induced pluripotent stem comprising expressing exogenous Sox-2, exogenous Klf-4, exogenous Oct3/4 from DNA that has not integrated into the genome of the somatic cell, suppressing p53 activity within the somatic cell, and exposing the somatic cell to reprogramming-assistance factors comprising an exogenous Alk-5 inhibitor, an exogenous histone deacetylase inhibitor, and an exogenous activator of glycolysis. Compositions and kits for use in such methods are also disclosed as are cells made by such a method.

This application relates to non-human primate (NHP) induced pluripotent stem cell (IPSC)-derived hepatocytes and methods of producing the same. Moreover, this application relates to methods of using NHP IPSC-derived hepatocytes for drug screening, drug safety assessment and in models of infection.

In vitro biomimetic models of the neonatal immune system are provided along with methods of using the models in pre-clinical assessment of infant immune cell-mediated and humoral responses to immunogenic stimulation, such as vaccination. The models include one comprising cord blood-derived T follicular helper cells and B cells, and one comprising cord blood-derived dendritic cells and CD4+ T cells. The models can be used, for example, to assess candidate vaccines via analysis of cellular responses to antigen and vaccine exposure.

A method is provided for uniformly differentiating a pluripotent stem cell into a neural stem cell, with elimination of variation among cell strains or clones of the pluripotent stem cell and without formation of an embryoid body, regardless of the origin of the pluripotent stem cell

Novel MSC stem-cell culture and therapy methods and culture medium compositions for the purpose of inducing, activating, or priming discrete uniform cell phenotypes to selectively promote or suppress inflammation and immunity, yielding polarized, primed, activated, or induced cells used in cell-based therapy.

Provided herein are methods for the in vitro differentiation of induced pluripotent stem cells, which have been expanded and/or maintained under defined conditions, into endodermal precursor cells (EPCs) that are capable of producing mono-hormonal beta cells.

Described herein are methods for the production of extracellular vesicles comprising culturing a population of producer cells in single-cell suspension, wherein the cells are cultured in chemically-defined culture medium, wherein the culture medium lacks animal-derived serum and animal-derived components; and obtaining from the cell culture an extracellular vesicle preparation comprising extracellular vesicles. In certain embodiments, the methods comprise perfusion culturing methods, including single-cell perfusion culturing methods and batch-refeed culturing methods. The methods described herein are a significant improvement over the state of the art and fulfills an unmet need in the field of extracellular vesicle manufacturing and quality control.

The present disclosure relates to the use of laminin-521 in obtaining retinal pigment epithelium (RPE) cells. Pluripotent human embryonic stem cells are cultured on plates coated with recombinant laminin-521 (laminin-11), in totally defined and xeno-free conditions. A first cell culture medium contains a growth factor, and a second cell culture medium does not contain growth factor. The stem cells are first exposed to the first cell culture medium, then exposed to the second cell culture medium for a longer time period. After a number of weeks, clinical grade RPE cells are obtained from the stem cells.