Abstract: This invention relates to methods of producing a population of progenitor T cells comprising differentiating haematopoietic progenitor cells (HPCs) into progenitor T cells in the presence of a pyrimidoindole compound, such as methyl 4-(3-piperidin-1-ylpropylamino)-9H-pyrimido[4,5-b] indole-7-carboxylate (UM729) or (1R,4R)-N1-(2-benzyl-7-(2-methyl-2H-tetrazol-5-yl)-9H-pyrimido[4,5-b]indol-4-yl)cyclohexane-1,4-diamine (UM171). The progenitor T cells may be matured, activated and expanded, for example for use in immunotherapy.

Abstract: This invention concerns chemically defined haematopoietic induction media that support the differentiation of haemogenic endothelial cells (HECs) into haematopoietic progenitor cells (MFCs) that are capable of further differentiation into T cells. The media may (a) stimulate cKIT receptor and/or cKIT receptor mediated signalling pathways and/or (b) stimulate VEGFR and/or VEGFR mediated signalling pathways. For example, the medium may comprise SCF and VEGF. In some embodiments, the media may further (c) stimulate MPL or MPL mediated signalling pathways; (d) stimulate FLT3 or FLT3 mediated signalling pathways (e) stimulate IGF1R or IGF1R mediated signalling pathways and (f) display interleukin (IL) activity. For example, the medium may further comprise Thrombopoietin (TPO), Fits ligand (FltSL), IGF-1, IL-3, IL-6 and optionally IL-7. These media may be useful for example in the production of blood cells or use in immunotherapy.

Abstract: This invention relates to the production of a population of haemogenic progenitor cells by (i) differentiating a population of induced pluri potent stem cells (IPSCs) into mesoderm cells and; (II) differentiating the mesoderm cells to produce a population of haemogenic progenitor cells. Steps (i) and (ii) are performed without purification or isolation of cells in the population. In addition, the haemogenic progenitor cells may be produced without the use of serum or stromal co-culture. Methods of the invention may be useful for example, in the production of clinical grade blood cells, such as T cells, for use in immunotherapy.

Abstract: A method for manufacturing a heat conducting substrate includes providing a metal plate with a first surface and an opposed second surface; forming a plurality of micro bumps on the first surface; disposing an adhesive layer on the first surface among the micro bumps; providing a circuit layer with a plurality of first openings formed thereon, positions of the first openings corresponding to positions of the micro bumps; fixing the circuit layer onto the adhesive layer, wherein the micro bumps are exposed through the first openings respectively; manufacturing circuits on the circuit layer; and finally, thinning a thickness of the metal plate. The method for manufacturing a heat conducting substrate has the manufactured heat conducting substrate to meet the requirements of being thin-shaped and having high heat conducting electronic elements, and has the advantage of an improved yield.