The present disclosure relates to compositions, vectors, constructs, cells and methods for the reprogramming of cells into natural killer (NK) cells or progenitors. In particular, it relates to a combination of transcription factors for the reprogramming of cells.

This disclosure relates a composition and method for promoting the reprogramming of somatic cells to induced pluripotent stem cells, the composition comprising gelatin and laminin. The disclosure further relates to a method of preparing somatic cells for producing induced pluripotent stem cells and a method for producing induced pluripotent stem cells, and thus provides method useful for the production of expanded somatic cells and induced pluripotent stem cells for use in research and therapy. Thus, the disclosure provides a method of preparing somatic cells for producing induced pluripotent stem cells, the method comprising: (i) isolating somatic cells from a sample, and (ii) expanding the somatic cells for a predetermined period of time, wherein the expanded somatic cells express TERT1, as well as a method for producing induced pluripotent stem cells from said expanded somatic cells by (a) introducing genetic elements, optionally episomal genetic elements, that express induced pluripotent stem cells reprogramming factors into said expanded somatic cells and (b) culturing said expanded somatic cells comprising the genetic elements, thereby producing induced pluripotent stem cells.

Methods for producing megakaryocytes and platelets derived from inducible pluripotent stem cells are provided. Such megakaryocytes or platelets can be genetically modified to comprise a nucleic acid molecule encoding a therapeutic agent. The present disclosure further provides methods and compositions for loading a platelet or a megakaryocyte with a therapeutic agent and for genetically modifying a platelet or a megakaryocyte to express an agent.

This invention provides methods of generating natural killer (NK) cells and dendritic cells (DCs). The methods utilize human hemangioblasts as intermediate cells to generate the NK cells and DCs. In various embodiments, the methods do not require the use of stromal feeder layers.

The present invention relates to a method for inducing the differentiation of hematopoietic stem cells or macrophages by using pluripotent stem cells, and a composition for inducing the differentiation. Specifically, the present invention relates to a composition for inducing the differentiation of hematopoietic stem cells comprising bone morphogenetic protein 4 (BMP4) in pluripotent stem cells, or a composition for inducing the differentiation of macrophages comprising BMP4 and a macrophage-colony stimulating factor (M-CSF), and a method for inducing the differentiation by using the compositions. The method for inducing the differentiation of the present invention is advantageous in that a differentiation method thereof is simple since only a few types of cytokine are used, and compared to conventional methods for inducing the differentiation, the efficiency of differentiation is improved tens of times or more and the yield of differentiated cells is high.

Provided herein are methods for the production of antigen-specific effector T cells and NK cells from pluripotent stem cells which express a chimeric antigen receptor (CAR). Further provided herein are methods for the adoptive cell therapy by administering the effector T cells and/or NK cells provided herein.

Compositions and methods for manufacturing induced immune regulatory cells comprising induced myeloid suppressive cells including MDSCs (myeloid-derived suppressor cells), dendritic cells, macrophages, and subpopulations thereof are provided. Also provided are methods and compositions for further modifying and modulating the induced immune regulatory cells to achieve enhanced therapeutic potential in treating autoimmune disorders, hematological malignancies, solid tumors, viral infections, neurodegenerative disorders, inflammatory conditions, or GvHD.

The present disclosure relates to a stage-specific process for manufacturing a population of neutrophils, such as chimeric antigen receptor-expressing (CAR-expressing) neutrophils (e.g., T cells and natural killer (NK) cells), from human pluripotent stem cells (hPSCs) using defined media and related compositions, kits, and methods of use (e.g., targeted cancer immunotherapy). Stage-specific processes for generating neutrophils and chimeric antigen receptor (CAR) neutrophils from human pluripotent stem cells (hPSCs) using chemically defined, feeder-free platforms and stage-specific morphogens; cell lines; pharmaceutical compositions; a method of treating cancer; and a kit are within the scopes of this disclosure.

The present invention relates to a method of preparing hematopoietic cell graft or enriching a population of cells for hematopoietic stem cells that are capable of long-term multilineage engraftment and self-renewal. It also relates to hematopoietic grafts comprising said hematopoietic stem cells as well as their uses in therapy.

Methods for generating and using hematopoietic progenitor cells are described.