Provided herein are methods and customized media compositions for culturing CIK NKT cells.

Methods of generating definitive hematopoietic cells from source cells including at least one of: differentiating iPS cells, cells directly reprogrammed to pre-cursors of hematopoietic cells, cells directly reprogrammed to definitive hematopoietic cells, and adult or neonatal hematopoietic cells from bone marrow, cord blood, placenta, or mobilized peripheral blood, the method including using a metabolic regulator to activate a tricarboxylic acid cycle of the source cells. Other methods relate to generating primitive hematopoietic cells from source cells including at least one of: differentiating iPS cells, cells directly reprogrammed to pre-cursors of hematopoietic cells, cells directly reprogrammed to definitive hematopoietic cells, and adult or neonatal hematopoietic cells from bone marrow, cord blood, placenta, or mobilized peripheral blood, the method including using a metabolic regulator to inhibit a tricarboxylic acid cycle of the source cells. Some aspects relate to a metabolic regulator for activation of a tricarboxylic acid cycle of source cells for the production of definitive or primitive hematopoietic cells.

The disclosure features methods and compositions for differentiating stem cells into hematopoietic stem and progenitor cells (HSPC) and/or Natural Killer (NK) cells. The methods and compositions described herein are used to differentiate stem or progenitor cells having at least one gene-edit that is maintained in the differentiated cell. Also provided are differentiated cells produced using the methods and compositions described herein for therapeutic applications.

Provided are methods for expanding stem cells and/or lineage committed progenitor cells, such as hematopoietic stems cells and/or lineage committed progenitor cells, at least in part, by using compounds that antagonize AhR. The compounds are represented by formulae:

##STR00001## wherein the letters and symbols a, b, c, d, e, f, g, Z, R.sup.1b, R.sup.2a and R.sup.2b have the meanings provided in the specification. Also provided are compositions comprising stem cells and/or lineage committed progenitor cells expanded by methods disclosed herein and methods for the treatment of diseases treatable by same.

The present invention relates to the field of medicine, specifically the field of treatment of cancer. More specifically, the invention relates to a method for the ex vivo production of a population of highly functional NK cells from CD34-positive cells, to a population of highly functional NK cells obtained and to the use of such population of highly functional NK cells for adoptive cell therapy.

The present invention relates to, inter alia, an engineered cell (e.g., iPSC, IPS-derived NK, or NK cell) comprising a disrupted B2M gene and an inserted polynucleotide encoding one or more of SERPINB9, a fusion of IL15 and IL15Rα, and/or HLA-E. The engineered cell can further comprise a disrupted CIITA gene and an inserted polynucleotide encoding a CAR, wherein the CAR can be an anti-BCMA CAR or an anti-CD30 CAR. The engineered cell may further comprise a disrupted ADAM17 gene, a disrupted FAS gene, a disrupted CISH gene, and/or a disrupted REGNASE-1 gene. Methods for producing the engineered cells are also provided, and therapeutic uses of the engineered cells are also described. Guide RNA sequences targeting described target sequences are also described.

A hydrogel capsule comprising a stem cell core that has been induced to differentiate into a hematopoietic lineage cell, and methods for the production of hematopoietic lineage cells from stem cells encapsulated in a hydrogel.

The invention provides culture platforms, cell media, and methods of differentiating pluriptent cells into hematopoietic cells. The invention further provides pluripotent stem cell-derived hematopoietic cells generated using the culture platforms and methods disclosed herein, which enable feed-free, monolayer culturing and in the absence of EB formation. Specifically, pluripotent stem cell-derived hematopoietic cell of this invention include, and not limited to, iHSC, definitive hemogenic endothelium, hematopoietic multipotent progenitors, T cell progenitors, NK cell progenitors, T cells, and NK cells.

Methods for using cyclin-dependent kinase (CDK) inhibitors to enhance growth and self-renewal of progenitor cells, in vitro and in vivo.

The following are disclosed: a method for producing a T cell progenitor, including step (1) of culturing CD34.sup.+ cell in a medium containing an aryl hydrocarbon receptor antagonist, a medium for T cell progenitor differentiation containing an aryl hydrocarbon receptor antagonist, and a T cell progenitor inducer containing an aryl hydrocarbon receptor antagonist.