Methods, kits and compositions for differentiating pluripotent stem cells into cells of endothelial and hematopoietic lineages are disclosed.

The present disclosure relates to compositions, nucleic acid constructs, methods and kits thereof for cell induction or reprogramming cells to the dendritic cell state or antigen presenting cell state, based, in part, on the surprisingly effect described herein of novel use and combinations of transcription factors that permit induction or reprogramming of differentiated or undifferentiated cells into dendritic cells or antigen presenting cells. Such compositions, nucleic acid constructs, methods and kits can be used for inducing dendritic cells in vitro, ex vivo, or in vivo, and these induced dendritic cells or antigen presenting cells can be used for immunotherapy applications.

The present invention in general relates to a method of differentiating human hematopoietic stem cells (HSC) into mature natural killer (NK) cells; wherein said method is in particular characterized in that mature NK cells are obtainable very early during the differentiation method, and that these NK cells display increased CD16 expression and antibody-dependent cellular cytotoxicity (ADCC) (FIG. 11). The method of the invention specifically encompasses transfecting and/or transducing HSCs with at least one transcription factor selected from T-Box expressed in T cells (T-BET) and Eomesodermin (EOMES); or a combination thereof.

Embodiments of the instant disclosure relate to novel compositions, methods and systems for generating ILC cells. In certain embodiments, the present disclosure provides for a composition including a hematopoietic progenitor cell expressing CD48 and at least one of a CD48 ligand, a CD48 agonist or a CD48 antagonist in order to induce production of ILC2 or ILC3 (for example, NCR.sup.+ ILC3 and LTi-ILC3) cell populations. In other certain embodiments, the present disclosure provides methods of treating one or more health condition or immune-mediated condition in a subject by administering an effective amount of a composition of ILC2 or ILC3 cells generated using methods disclosed herein.

The present disclosure relates to compositions, nucleic acid constructs, methods and kits thereof for cell induction or reprogramming cells to the dendritic cell state or antigen presenting cell state, based, in part, on the surprisingly effect described herein of novel use and combinations of transcription factors that permit induction or reprogramming of differentiated or undifferentiated cells into dendritic cells or antigen presenting cells. Such compositions, nucleic acid constructs, methods and kits can be used for inducing dendritic cells in vitro, ex vivo, or in vivo, and these induced dendritic cells or antigen presenting cells can be used for immunotherapy applications.

Disclosed are populations of dendritic cells generated from stem cells capable of inducing immunity towards cancer. In one embodiment said dendritic cells are generated from allogeneic inducible pluripotent stem cells, for some uses, said pluripotent stem cells are genetically engineered/edited to induce cancer specific immunity and/or resist immunosuppressive effect of tumor derived microenvironment. In one embodiment pluripotent stem cells are transfected with cancer stem cell antigens such as BORIS and/or NR2F6.

The present invention provides a pluripotent stem cell comprising a co-expression vector in which Runx1 and Hoxa9 are of in tandem, and a T cell differentiated therefrom and application thereof. In the present invention, Pluripotent stem cells inducibly co-expressing exogenous Runx1 and Hoxa9 are successfully established by introducing an exogenous vector co-expressing Runx1 and Hoxa9 into pluripotent stem cells. The pluripotent stem cells are directionally differentiated into T-lineage progenitor cells and will be developed into T cells. The pluripotent stem cell-derived T cells obtained by the method of the present invention are not only functionally normal but also have no tumorigenic risk.

The present invention provides a pluripotent stem cell comprising a co-expression vector in which Runx1 and Hoxa9 are of in tandem, and a T cell differentiated therefrom and application thereof. In the present invention, Pluripotent stem cells inducibly co-expressing exogenous Runx1 and Hoxa9 are successfully established by introducing an exogenous vector co-expressing Runx1 and Hoxa9 into pluripotent stem cells. The pluripotent stem cells are directionally differentiated into T-lineage progenitor cells and will be developed into T cells. The pluripotent stem cell-derived T cells obtained by the method of the present invention are not only functionally normal but also have no tumorigenic risk.

Provided are methods for isolating potent extracellular vesicle or exosome populations from mesenchymal stromal cells, and the use of the isolated extracellular vesicles or exosomes in treating vasculopathy, including pulmonary hypertension, bronchopulmonary dysplasia, and disease and conditions associated with mitochondrial dysfunction.

Systems and methods for the dynamic co-culturing of two cell populations are provided. The system includes a barrier configured to physically separate a stimulator cell population from a responder cell population disposed within a container. The barrier is permeable to the secreted factors of at least one of the cell populations. The responder cell population can thereby be altered by exposure to the secreted factors to produce a population of reprogrammed cells that includes biomolecules (e.g., nucleic acids) originating from the stimulator cell population and/or that exhibits one or more additional or modified functional activities than a parental population of the reprogrammed cells.