The present invention refers to a method for inducing pluripotent stem cells starting from somatic cells isolated from healthy and/or diseased individuals. The diseased individual is preferably affected by a genetic disease such as type A hemophilia, and the somatic cells from the diseased individual are genetically corrected for the mutation causing the disease preferably after being reprogrammed by the method of the present invention. A further aspect of the present invention refers to a method for differentiating induced pluripotent stem cells or embryonic stem cell-like into endothelial cells. Moreover, the present invention refers to the use of these cells as a medicament for treating a disease, in particular, a genetic disease such as type A hemophilia.

The present invention relates in part to nucleic acids encoding proteins, nucleic acids containing non-canonical nucleotides, therapeutics comprising nucleic acids, methods, kits, and devices for inducing cells to express proteins, methods, kits, and devices for transfecting, gene editing, and reprogramming cells, and cells, organisms, and therapeutics produced using these methods, kits, and devices. Methods for inducing cells to express proteins and for reprogramming and gene-editing cells using RNA are disclosed. Methods for producing cells from patient samples, cells produced using these methods, and therapeutics comprising cells produced using these methods are also disclosed.

The invention relates to an isolated cell having, after culturing a pluripotent stem cell (PSC) in a medium comprising a WNT agonist and an ACTIVIN antagonist, increased HOXA gene expression relative to a PSC not cultured in a medium comprising a WNT agonist and an ACTIVIN antagonist, wherein the cell with increased HOXA gene expression is capable of generating a definitive haematopoietic stem/precursor cell. The invention also relates to use of the cell for generating a definitive haematopoietic stem/precursor cell, and a method for differentiating a PSC into a definitive haematopoietic stem/precursor cell and a definitive haematopoietic stem/progenitor cell differentiated from a PSC by the method. The invention further relates to a therapeutic composition comprising a cell of the invention, and to therapeutic methods and uses of a cell of the invention. The invention also relates to a reporter cell comprising distinguishable SOX17 and RUNXIC reporters, for use in tracking the differentiation of a PSC into a definitive haematopoietic stem/progenitor cell.

Methods of generating and expanding human hemangio-colony forming cells in vitro and methods of expanding and using such cells are disclosed. The methods permit the production of large numbers of hemangio-colony forming cells as well as derivative cells, such as hematopoietic and endothelial cells. The cells obtained by the methods disclosed may be used for a variety of research, clinical, and therapeutic applications.

The invention relates to an in vitro method to generate T cell progenitors, comprising the step of culturing CD34+ cells in a medium containing TNF-alpha and/or an antagonist of the Aryl hydrocarbon/Dioxin receptor, in particular StemRegenin 1 (SR1), in presence of a Notch ligand and optionally a fibronectin fragment.

The present invention is in the field of pluripotent stem cells. In particular the invention relates to a method for (closed system) induction of differentiation of pluripotent stem cells towards a pre-selected cell type, such as, for example, cardiomyocytes or endothelial cells. The method as disclosed herein is particularly useful to upscale the production of cells derived from pluripotent stem cells, in particular (human) cardiomyocytes and/or endothelial cells derived from pluripotent stem cells.

The present invention relates in part to nucleic acids encoding proteins, nucleic acids containing non-canonical nucleotides, therapeutics comprising nucleic acids, methods, kits, and devices for inducing cells to express proteins, methods, kits, and devices for transfecting, gene editing, and reprogramming cells, and cells, organisms, and therapeutics produced using these methods, kits, and devices. Methods for inducing cells to express proteins and for reprogramming and gene-editing cells using RNA are disclosed. Methods for producing cells from patient samples, cells produced using these methods, and therapeutics comprising cells produced using these methods are also disclosed.

The invention relates to an in vitro method to generate T cell progenitors, comprising the step of culturing CD34+ cells in a medium containing TNF-alpha and/or an antagonist of the Aryl hydrocarbon/Dioxin receptor, in particular StemRegenin 1 (SR1), in presence of a Notch ligand and optionally a fibronectin fragment.

The invention relates to an in vitro method to generate T cell progenitors, comprising the step of culturing CD34+ cells in a medium containing TNF-alpha and/or an antagonist of the Aryl hydro-carbon/Dioxin receptor, in particular StemRegenin 1 (SR1), in presence of a Notch ligand and optionally a fibronectin fragment.

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