The present invention relates to methods, kits and compositions for expansion of hematopoietic stem/progenitor cells and providing hematopoietic function to human patients in need thereof. In one aspect, it relates to kits and compositions comprising a Notch agonist and an aryl hydrocarbon receptor antagonist. Also provided herein are methods for expanding the hematopoietic stem/progenitor cells using kits and compositions comprising a Notch agonist and an aryl hydrocarbon receptor antagonist. The hematopoietic stem/progenitor cells expanded using the disclosed kits, compositions and methods include human umbilical cord blood stem/progenitor cells, placental cord blood stem/progenitor cells and peripheral blood stem cells. The present invention also relates to administering hematopoietic stem/progenitor cells expanded using a combination of a Notch agonist and an aryl hydrocarbon receptor antagonist to a patient for short-term and/or long-term in vivo repopulation benefits.

The present disclosure provides methods for generating megakaryocytes and novel platelet variants from the same CD34+ progenitor stem cells, which comprises at least two stages: stage zero (0) comprising an expansion and maintenance stage of the CD34+ progenitor stem cells for a period ranging between 0 hours to 48 hours; and, stage one (I) comprising a differentiation phase wherein the differentiation phase comprises differentiating the CD34+ progenitor stem cells in step (i) for a period sufficient to generate substantially matured megakaryocytes. Novel platelet variants are produced by passaging the megakaryocytes, produced by the CD34+ progenitor stem cells, through a bioreactor or a fluidic device. Formulations comprising megakaryocytes and platelet variants derived from CD34+ progenitor stem cells and methods of their use are also disclosed.

There is described herein a method of enriching a population of stem cells for hematopoietic progenitors. The method comprises inducing hematopoietic differentiation in a population of human embryonic stem cells or human induced pluripotent stem cells; sorting the population based on expression of CD43 and at least one of CD34, CD31 and CD144; and selecting a fraction that is at least one of CD34+CD43−, CD31+CD43− and CD144+CD43−. Also provided are populations of hematopoietic progenitors obtained by the methods described herein.

Alveolar-like macrophages and a method for generating alveolar-like macrophages from hemangioblasts is provided. The method comprises the steps of: i) culturing the hemangioblasts in a hematopoietic-inducing medium comprising vascular endothelial growth factor (VEGF), stem cell factor (SCF) and interleukin-3 (IL-3) for a sufficient period of time to generate macrophages, and ii) culturing the macrophages in an alveolar macrophage-inducing medium comprising granulocyte macrophage colony stimulating factor (GM-CSF), and optionally macrophage colony stimulating factor (M-CSF), under suitable conditions and for a sufficient period of time to yield alveolar-like macrophages.

The present description relates to in vitro methods for culturing hematopoietic stem cells (HSCs) under mild hyperthermia conditions (e.g., between 38° C. and 40° C.) in the presence of a pyrimidoindole derivative agonist of hematopoietic stem cell expansion. The combined use of mild hyperthermia and the pyrimidoindole derivative act synergistically to promote expansion of CD34+ HSCs and/or differentiation into progenitor cells (e.g., megakaryocytic progenitors). The present description also relates to in vitro expanded cell populations of HSCs and/or progenitors, as well as uses thereof in therapy (e.g., transplantation).

The present invention provides a method for efficiently inducing CD8-positive T cells by adding vitamin C to the medium in the steps of induction of the CD8-positive T cells from pluripotent stem cells. The present invention also provides a method for efficiently inducing CD8-positive T cells by performing culture in a medium supplemented with an adrenocortical hormone agent in the step of induction of the CD8-positive T cells from CD4/CD8 double-positive T cells.

Methods for maintaining and expanding human CD34+ hematopoietic stem cells (HSCs) are provided using chemically-defined culture media that allow for expansion of HSCs in as little as six days. Culture media, isolated cell populations and kits are also provided.

Methods for obtaining purified populations of megakaryocytes and platelets by ex vivo culture of stem cells are provided herein.

Disclosed are methods for conditionally immortalizing stem cells, including adult and embryonic stem cells, the cells produced by such methods, therapeutic and laboratory or research methods of using such cells, and methods to identify compounds related to cell differentiation and development or to treat diseases, using such cells. A mouse model of acute myeloid leukemia (AML) and cells and methods related to such mouse model are also described.

The present disclosure relates to methods for expansion of stem cell populations using a polypeptide that enhances stem cell growth and proliferation. The present disclosure further relates to novel homeobox protein mutants (e.g., HOXA9 and HOXB4 mutant proteins) and the use thereof to expand certain stem cell populations. The present disclosure also provides methods for treating a subject in need of transplantation of stem cells.