This invention relates to hematopoietic precursors derived from human embryonic stem cells. In the culture of differentiated cells from human ES cells, the fully committed hematopoietic precursors are CD34+ and CD43+ but not CD45+. If the cells are cultured until they express CD45, then the cells lose the ability to produce differentiated cells of the lymphoid lineages.

The present disclosure relates to composition comprising pooled and expanded allogeneic mesenchymal Stromal cells (MSCs) and a method for management of Ischemia using the composition thereof. In particular, the disclosure relates to bone marrow derived pooled and expanded allogeneic MSC compositions with effective dosage ranges and modes/route of administration for effective management of Ischemia. The disclosure also relates to the use of conditioned medium rich in bioactive factors in combination with the cell composition for managing ischemic conditions.

The invention relates to natural killer cells and methods for the development of immortalized natural killer cells and use of the natural killer cells. A growth and culture system is described that supports increased natural killer cell development, and provides for the establishment of continuous natural killer cell lines. Additionally, the disclosed method for generating natural killer cells may be used to produce large numbers of natural killer cells for therapeutic applications and for natural killer cell research.

The inventive subject matter relates to methods for treating a T-cell deficiency in a subject in need thereof, comprising administering to said subject a T-cell precursor isolated from an allogeneic donor, provided that said allogeneic donor is not MHC-matched to said subject. The inventive methods can be further enhanced by genetic engineering for targeted immunotherapy.

The disclosure relates to the development of methods for making hematopoietic stem cells from differentiated cells by introducing and expressing transcription factors. More particularly, the disclosure provides methods for redirecting differentiated cells to a hematopoietic stem cell state or to a hemogenic endothelial cell state by direct programming with specific combinations of transcription factors.

Human progenitor T cells that are able to successfully engraft a murine thymus and differentiate into mature human T and NK cells are described. The human progenitor T cells have the phenotype CD34+CD7+CD 1aCD5 or CD34+CD7+CD1aCD5+ and are derived from human hematopoietic stem cells, embryonic stem cells and induced pluripotent stem cells by coculture with cells expressing a Notch receptor ligand (OP9-DL1 or OP9-DL4). Such cells are useful in a variety of applications including immune reconstitution, the treatment of immunodeficiencies and as carriers for genes used in gene therapy.

The present invention refers to a novel and efficient method for large-scale selective generation of y T cells, preferably human V1+y T cells, optimal for clinical application in adoptive immunotherapy of cancer. In this sense, considering that both human cord blood HPCs, currently elected as source of stem cells in the clinic, and human early thymic progenitors can efficiently generate de novo human y T cells in response to Notch signalling, and most efficiently in response to the Notch ligand Jag2, the method thus comprises inducing the differentiation of cord blood CD34+ hematopoietic progenitor cells (HPCs) and/or human CD34+ early thymic progenitors, by activating them with Jag2 Notch ligands.

The present invention relates to compositions and methods in the context of mitochondrial transfer. Disclosed herein are methods that enable the efficient transfer of mitochondria from a donor cell to a recipient cell. The mitochondria-augmented cells are useful in the treatment of diseases and disorders, such as cancer. The present invention also relates to the molecular machinery involved in mitochondrial transfer.

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