The present invention relates to the ex vivo differentiation of NK cells from CD34+ hematopoietic stem cells. Such NK cells and their progenitor cells can be used in therapies of a broad range of malignancies. In the present invention it is shown that IL-12 modulates ex vivo NK cell differentiation. Specific, we achieved significantly higher expression of KIR, CD16 and CD62L in the presence of IL-12 in the cell culture system. The induction of receptor expression by IL-12 occurred predominantly on an augmented population of CD33+NKG2A+ NK cells early during NK cell differentiation. These cells further show enhanced cytolytic activity against MHC class I positive AML targets. In line with the enhanced CD16 expression, IL-12 modulated ex vivo generated NK cells exhibit an improved antibody-dependent-cytotoxicity, using anti CD20 antibody on various B cell targets. Additional to the enhanced expression of CD62L, we show that this cell population consists of a specific chemokine receptor profile. By showing an increased capacity for adhesion to lymphendothelial cells and a specific chemokine receptor profile, we show that IL-12 provided the ex vivo generated NK cells with specific tissue-homing abilities.

Methods for producing megakaryocytic progenitors (preMKs) and megakaryocytes (MKs) from stem cells are provided. The present disclosure further provides compositions comprising preMKs and MKs and their lysates, and also methods of use of preMKs, MKs, their lysates and compositions thereof.

A method has been developed to enhance the efficacy of cancer vaccines by activating the immune system against a greater variety of antigens expressed in the tumor cells. In this modification, the vaccine is created against not only the more mature cancer cells, but also cancer stem cells (CSCs), that act as tumor propagating cells, and can also be made against as the more mature progeny of the CSCs that are normally present within the malignant tumors in numbers which are too low to effectively manufacture a vaccine against their antigens, but which are responsible for recurrence of the malignant tumor. These include pluripotent and stem cells induced from cells in a tumor biopsy by exposure to stress inducing agents that cause the cells to almost die, thereby causing cells to de-differentiate. The method greatly increases the variety of the tumor antigens at which the vaccine is targeted.

An additive for culturing stem cells containing a polysaccharide other than dextran sulfate having a molecular weight of 4,000 kDa to 40,000 kDa, a medium for culturing stem cells, containing a polysaccharide other than dextran sulfate having a molecular weight of 4,000 kDa to 40,000 kDa, and a method for culturing a stem cell, including suspension culturing the stem cell in a medium for culturing stem cells containing a polysaccharide other than dextran sulfate having a molecular weight of 4,000 kDa to 40,000 kDa are useful for suspension culture of stem cells, in which the forming rate of cell aggregates of the stem cells can be improved, the shape thereof can be controlled, and also the proliferation rate and the rate of maintaining an undifferentiated state of the stem cells can be improved.

A method is provided for simultaneously producing both nephron progenitor cells and ureteric epithelial progenitor cells including the step of contacting intermediate mesoderm cells with: fibroblast growth factor (9) and/or fibroblast growth factor (20) and optionally, one or more selected from the group consisting of. bone morphogenic protein 7; heparin: a Wnt agonist; retinoic acid; and an RA antagonist. The concentrations of Writ agonist, retinoic acid and/or RA antagonist may be manipulated to favour the relative production of nephron progenitor cells and ureteric epithelial progenitor cells. The intermediate mesoderm cells are ultimately derived from human pluripotent stem cells via a posterior primitive streak stage. The nephron progenitor cells and ureteric epithelial progenitor cells may have end uses such as for kidney repair and regeneration, bioprinting of kidneys and screening compounds for nephrotoxicity.

Methods for production of platelets from pluripotent stem cells, such as human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs) are provided. These methods may be performed without forming embryoid bodies or clusters of pluripotent stem cells, and may be performed without the use of stromal inducer cells. Additionally, the yield and/or purity can be greater than has been reported for prior methods of producing platelets from pluripotent stem cells. Also provided are compositions and pharmaceutical preparations comprising platelets, preferably produced 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.

Provided herein are methods of treating a hematological disorder, a solid tumor, or an infectious disease in a subject in need thereof using natural killer cells in combination with a second agent, or using natural killer cells with genetic modifications for target specificity and/or homing specificity.

The present invention provides muscle-derived progenitor cells that show long-term survival following transplantation into body tissues and which can augment soft tissue following introduction (e.g. via injection, transplantation, or implantation) into a site of soft tissue. Also provided are methods of isolating muscle-derived progenitor cells, and methods of genetically modifying the cells for gene transfer therapy. The invention further provides methods of using compositions comprising muscle-derived progenitor cells for the augmentation and bulking of mammalian, including human, soft tissues in the treatment of various cosmetic or functional conditions, including malformation, injury, weakness, disease, or dysfunction. In particular, the present invention provides treatments and amelioration of symptoms for gastro-esophageal pathologies like gastro-esophageal reflux.

A method of generating a population of cells useful for treating a brain disorder in a subject is disclosed. The method comprises contacting mesenchymal stem cells (MSCs) with at least one exogenous miRNA having a nucleic acid sequence at least 90% identical to a sequence selected from the group consisting of SEQ ID NOs: 15-19 and 27-35, thereby generating a population of cells and/or generating neurotrophic factors that may provide important signals to damaged tissues or locally residing stem cells. MSCs differentiated by miRs may also secrete miRs and deliver them to adjacent cells and therefore provide important signals to neighboring endogenous normal or malignant cells.