Abstract: A culture medium for inducing a pluripotent stem cell into a differentiation-promoted pluripotent stem cell, the medium including a Glycogen synthase kinase 3? (GSK3?) inhibitor, a Bone morphogenic protein (BMP) signaling inhibitor, and a Transforming growth factor (TGF)-? inhibitor as active ingredients.

Abstract: The generation of complex organ tissues from human embryonic and pluripotent stem cells (PSCs) remains a major challenge for translational studies. It is shown that PSCs can be directed to differentiate into intestinal tissue in vitro by modulating the combinatorial activities of several signaling pathways in a step-wise fashion, effectively recapitulating in vivo fetal intestinal development. The resulting intestinal “organoids” were three-dimensional structures consisting of a polarized, columnar epithelium surrounded by mesenchyme that included a smooth muscle-like layer. The epithelium was patterned into crypt-like SOX9-positive proliferative zones and villus-like structures with all of the major functional cell types of the intestine. The culture system is used to demonstrate that expression of NEUROG3, a pro-endocrine transcription factor mutated in enteric anendocrinosis is sufficient to promote differentiation towards the enteroendocrine cell lineage.

Abstract: A chimeric antigen receptor is provided, including an extracellular segment, including a single-chain antibody region binding to an antigen human CD19 and a hinge region, a trans-membrane segment, including a trans-membrane domain of human CD8? linked to the hinge region of the extracellular segment and embedded in cell membrane of T lymphocyte, and an intracellular segment, including an intracellular domain of human CD8?, an intracellular domain of molecule 4-1BB and an intracellular domain of CD3 ? chain. The single-chain antibody region includes a heavy-chain variable region and a light-chain variable region of the single-chain antibody, the hinge region includes an extracellular domain of human CD8 alpha (CD8?) of 55 amino acid residues and three alanine residues (AAA) located at the N-terminal of the extracellular domain of human CD8?, and the intracellular domain of human CD8? includes seven amino acid residues and linked to the trans-membrane domain of human CD8?.

Abstract: It has been found that a cell cluster obtained by causing just isolated cells to adhere to each other secretes adiponectin after transplantation to the heart, and thereby has an excellent therapeutic effect on heart disease.

Abstract: Novel lentivirus packaging systems engineered with a synthetic gene network having a positive feedback loop to amplify the expression of virus genes are provided. When co-transfected into a host cell with a transfer plasmid and envelope vector, extremely high viral titers are achieved when compared to transfection of a host cell with conventional third generation packaging systems. Methods for enhancing production of lentivirus, compositions comprising high titer lentivirus, and therapeutic methods based on delivery of lentiviral nucleic acid to target cells are also provided.

Abstract: The present disclosure is generally related to methods for combining chemotherapy and immunotherapy for the treatment of a cancer.

Abstract: The invention features compositions comprising in vitro generated beta cells capable of glucose-stimulated insulin secretion, methods of inducing beta cell maturation from embryonic or induced pluripotent stem cell-derived beta-like cells, and methods of using in vitro generated beta cells for the treatment of type 1 diabetes, type 2 diabetes, or a related disorder.

Abstract: Embodiments provided herein relate to systems for synthetically-engineered reciprocal chromosomal translocation for gene insertion into a population of organisms such as insects.

Abstract: The present invention provides methods to promote the differentiation of pluripotent stem cells. In particular, the present invention provides methods to produce a population of cells, wherein greater than 10% of the cells in the population express markers characteristic of single hormonal pancreatic beta cells.

Abstract: The present invention provides methods for inducing tolerance and/or suppressing an immune response to an antigen by passing a cell suspension containing an anucleate cell through a constriction, wherein the constriction deforms the cell thereby causing a perturbation of the cell such that an antigen and/or tolerogenic factor enters the cell. In some embodiments, the anucleate cell is delivered to an individual and the antigen is delivered to and processed in a tolerogenic environment to induce tolerance and/or suppress an immune response to the antigen.

Abstract: The present invention relates to viral vectors and methods of their production and use.

Abstract: The present invention pertains to engineered immune cells, method for their preparation and their use as medicament, particularly for immunotherapy. The engineered immune cells of the present invention are characterized in that at least one gene selected from a gene encoding GCN2 and a gene encoding PRDM1 is inactivated or repressed. Such modified Immune cells are resistant to an arginine and/or tryptophan depleted microenvironment caused by, e.g., tumor cells, which makes the immune cells of the invention particularly suitable for immunotherapy. The invention opens the way to standard and affordable adoptive immunotherapy strategies using immune cells for treating different types of malignancies.

Abstract: Disclosed herein are cell cultures and enriched cell populations of endocrine precursor cells, immature pancreatic hormone-expressing cells and mature pancreatic hormone-expressing cells. Also disclosed herein are methods of producing such cell cultures and cell populations.

Abstract: Provided are methods of determining whether a mammalian subject having an inflammatory condition (e.g., an oral inflammatory condition) will respond positively to mesenchymal stem cell (MSC) therapy, as well as method of treating such inflammatory conditions by administering MSCs.

Abstract: 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.

Abstract: The present invention relates to novel compositions and methods to produce 3D organ equivalents of the brain (i.e. “mini-brains”). The invention also relates to methods of using human induced pluripotent stem cells, a combination of growth and other soluble factors and gyratory shaking. Cells from healthy or diseased donors or animals can be used to allow testing different genetic backgrounds. The model can be further enhanced by using genetically modified cells, adding micro-glia or their precursors or indicator cells (e.g. with reporter genes or tracers) as well as adding endothelial cells to form a blood-brain-barrier.

Abstract: The invention relates to a cellular microcompartment comprising successively, organized around a lumen, at least one layer of pluripotent cells, an extracellular matrix layer and an outer hydrogel layer. The invention also relates to processes for preparing such cellular microcompartments.

Abstract: This invention relates to modified T cells that inducibly express a bioactive molecule, such as IL-7, and constitutively expresses an antigen receptor, such as a T cell receptor or chimeric antigen receptor that binds to a tumour antigen. The modified T cells may comprise a nucleic acid construct that comprises a first nucleotide sequence encoding the bioactive molecule, a second nucleotide sequence encoding the antigen receptor; an inducible promoter operably linked to the first nucleotide sequence and a constitutive promoter operably linked to the second nucleotide. Nucleic acid constructs and vectors are provided, as well as T cells comprising such constructs and vectors and therapeutic methods and uses thereof.

Abstract: Embodiments herein relate to in vitro production methods of hematopoietic stem cell (HSC) and hematopoietic stem and progenitor cell (HSPC) that have long-term multilineage hematopoiesis potentials upon in vivo engraftment. The HSC and HSPCs are derived from pluripotent stem cells-derived hemogenic endothelia cells (HE) by non-integrative episomal vectors-based gene transfer.

Abstract: A method is provided for producing renal organoids comprising nephrons, ureteric bud and vasculature and/or progenitors of these. In one embodiment, the methods includes contacting intermediate mesoderm cells with: fibroblast growth factor 9 and/or fibroblast growth factor 20 and/or fibroblast growth factor 2 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 under conditions that promote formation of vascularized renal organoids. Another embodiment includes producing mesoderm cells by sequentially contacting pluripotent stem cells with a Wnt agonist and fibroblast growth factor 9 and/or fibroblast growth factor 20 and/or fibroblast growth factor 2, followed by a relatively short re-exposure to the Wnt agonist.