Related Patent Info

Provided is an undifferentiated stem cell-removing agent which comprises at least one kind of inhibitor selected from the group consisting of a fatty acid synthesis inhibitor, a fatty acid utilization inhibitor and a cholesterol synthesis inhibitor.

Provided is a method for producing differentiated corneal cells including corneal epithelial precursor cells, corneal epithelial cells and stratified corneal epithelium from pluripotent stem cells in the absence of feeder cells, through inducing first into eye precursor cells.

Provided is a method for culturing a pluripotent stem cell, comprising a step of making the pluripotent stem cell contact with laminin 421 or a fragment thereof, or laminin 121 or a fragment thereof, or a combination thereof.

Provided is a medium to stably, economically and safely culture stem cells having differentiation ability while maintaining undifferentiated state. The said medium contains at least one compound selected from the group consisting of a ROCK inhibitor, a PKC inhibitor, a histone methyltransferase inhibitor and a retinoic acid receptor agonist, and is free from growth factors or has a low growth factor concentration.

Provided is a method for efficiently producing microglia from pluripotent stem cells, comprising steps of (a) co-culturing a pluripotent stem cell with a feeder cell to obtain a blood progenitor cell, (b) co-culturing the obtained blood progenitor cell with a feeder cell in the presence of IL-3 and/or GM-CSF to obtain an embryonic monocyte, and (c) in the presence of M-CSF, co-culturing the obtained embryonic monocyte together with an astrocyte, or culturing the embryonic monocyte using an astrocyte supernatant.

The present invention provides a method for producing cells positive for PTF1A, which is considered to be a fate-determining gene for pancreatic development. The method comprises a step of culturing a PDX1-positive cell, which may be derived from an iPS cell,  in a medium containing at least one substance selected from the group consisting of (a) at least one selected from the group consisting of adenylate cyclase activators, cAMP phosphodiesterase inhibitors, and cAMP analogs, (b) steroids, and (c) nicotinamide.

The present invention provides a method for producing differentiated cells from pluripotent stem cells by EB method in a closed system on a larger scale, using a culture bag that has a perfluoropolymer disposed on the inner surface thereof.

Provided is a method for obtaining KRT7+/KRT15LOW hiPSC-derived sebocyte precursor cells from human iPS cells.

Methods are provided, in some aspects, for differentiating human pluripotent cells into midbrain dopaminergic neurons using a mono-SMAD inhibition.

Provided is a method for generating oligodendroglial lineage cells comprising steps of (a) providing human cells selected from the group consisting of neural progenitor cells, pluripotent stem cells, induced pluripotent stem cells and fibroblasts, (b) inducing expression of SOX10, optionally in combination with OLIG2 and/or NKX6.2 in the cells, and (c) culturing the cells; thereby generating the oligodendroglial lineage cells.

Provided is a population of engineered cardiomyocytes generated from mammalian pluripotent stem cells comprising at least one mutation associated with an in vivo cardiac phenotype.

The present invention provides a method for producing a motor neuron from a pluripotent stem cell, comprising steps of (1) introducing a single Sendai virus vector carrying a nucleic acid encoding Lhx3, a nucleic acid encoding Ngn2 and a nucleic acid encoding Isl1 into a pluripotent stem cell, and (2) culturing the pluripotent stem cell for 2 days or longer.

Provided is a method for generating spinal cord glutamatergic interneurons from a population of human pluripotent stem cells (hPSCs), comprising a step of culturing a first population of hPSCs in a neural induction medium comprising retinoic acid signaling pathway activator, a sonic hedgehog signaling pathway activator, and Notch signaling pathway inhibitor, wherein the culturing results in generation of a second population of cultured cells comprising CHX10+ V2a interneurons.

Provided is a method for generating and isolating cardiomyocytes derived from pluripotent or multipotent stem cells, comprising steps of (a) differentiating said stem cells into cardiovascular cells, thereby generating a sample comprising cardiomyocytes and non-cardiomyocytes, (b) labeling the non-cardiomyocytes of said sample with more than one antibody or antigen binding fragment thereof specific for antigens of non-cardiomyocytes, wherein said more than one antibody or antigen-binding fragment thereof is selected from the group consisting of antiCDIO, antiCD105, antiCD140b, antiCD61, antiCD44, antiCD141, and antiCD51/61, and (c) depleting said labeled non-cardiomyocytes from said sample.

The invention provides a method for differentiating pancreatic endoderm cells into functional beta cells expressing PDX1, NKX6.1, MAFA, UCN3 and SLC2A by use of one or more small molecule(s) selected from a defined group. The said pancreatic endoderm cells may be obtained by step-wise differentiation from pluripotent stem cells.

Provided is a method for producing a cell population comprising mast cells. The method comprises steps of (a) culturing a population of cells capable of differentiation into mast cells (preferably, induced pluripotent stem cells) that comprise a selectable reporter linked to Gata2 expression levels in said cells under conditions adapted to promote hematopoietic cell development, (b) isolating cells expressing Gata2, and (c) culturing said isolated cells on feeder cells, thereby obtaining a cell population comprising mast cells.

Provided is a method for producing a population of expanded myogenic progenitor cells, comprising steps of (a) culturing pluripotent stem cells (PSCs) in a medium supporting differentiation towards a myogenic lineage in the presence of (i) CHIR99021 in a certain concentration range, (ii) FGF2 in a certain concentration range, and optionally (iii) insulin-transferrin-selenium-ethanolamine, to thereby provide a cell culture comprising myogenic progenitors cells, (b) isolating from said cell culture C-Met+ and HNK1- myogenic progenitor cell, and (c) expanding said isolated cell in a medium comprising FBS and FGF2, to thereby provide a cell culture wherein at least 50% of said population are MyoD positive and Pax7 negative.

Provided is an in vitro method for inducing a gastric fundus tissue comprising steps of (a) contacting a mammalian definitive endoderm cell, which may be derived from an iPS cell, with a wnt activator, a FGF activator, a BMP inhibitor, and retinoic acid to form a 3D posterior foregut spheroid, (b) suspending said 3D posterior foregut spheroid in a basement membrane matrix with a growth factor, a wnt activator, a EGF activator, a BMP inhibitor, and retinoic acid to induce a fundic lineage comprising fundic-type gastric organoids (hFGOs), (c) culturing said hFGOs with a wnt activator and a EGF activator, then with FGF 10, and (d) contacting the cultured hFGOs with a MEK inhibitor to form gastric fundus tissue comprising a functional fundic cell.

Provided is a method for generating a pancreatic islet organoid comprising a step of culturing an iPSC-derived beta-like cell in a 3D matrix comprising gellan gum, thereby generating a pancreatic islet organoid. The method may further comprise a step of culturing the iPSC-derived beta-like cell with an adipose-derived stem cell and/or an endothelial cell.

Provided is an induced pluripotent stem cell derived from a blood mononuclear cell that expresses a therapeutic entity, such as antibodies and nucleic acids, under the control of a HBB (hemoglobin beta) gene locus. The said induced pluripotent stem cell may form an anucleated erythrocyte comprising the therapeutic entity.

Provided is an in vitro method for producing a population of differentiated cells expressing one or more proprioceptor marker from a population of stem cells, which may be a popularion of human iPSCs, comprising steps of contacting the stem cell population with TGFβ/Activin-Nodal inhibitor(s) and then Wnt activator(s) in a certain concentration range.

The present disclosure provides a method for generating progenitor T cells from stem and/or progenitor cells comprising a step of exposing the stem and/or progenitor cells to Notch Ligand Delta- like-4 (DL4) and vascular adhesion molecule 1 (VCAM-1) under conditions suitable to generate progenitor T cells.

Provided is a method for producing endocrine progenitor cells from pluripotent stem cells (PSCs), comprising steps of (a) incubating PSCs in culture medium comprising Wnt3a, Activin A, a TGF-β inhibitor, and KGF for 3-7 days, (b) exposing the cells resulting from step (a) to medium comprising retinoic acid (RA) for 2-3 days; and (c) culturing the cells resulting from step (b) in medium comprising RA, EGF, and KGF, thereby producing a culture comprising greater than 70% of PDX1+ NKX6.1+ endocrine progenitor cells. The method may further comprise steps of culturing the PDX1+ NKX6.1+ endocrine progenitor cells, thereby producing INS+ NKX6.1+GCG+ immature β-like cells, and then re-aggregating the immature β-like cells to produce mature functional βcells.

Provided is a method for inducing blood brain barrier properties in iPSC-derived brain microvascular endothelial cells (BMECs) to generate an isogenic blood brain barrier model, comprising a step of co-culturing iPSC-derived BMECs with a cell type selected from the group consisting of iPSC-derived astrocytes, iPSC-derived neurons, and combinations thereof.

Provided is a method for producing a population of intestinal midgut endoderm cells from human pluripotent stem cells. The method may comprise the steps of (a) culturing the human pluripotent stem cells in a first culture medium containing GDF-8 and a GSK3 inhibitor to produce definitive endoderm cells, (b) culturing the definitive endoderm cells in a second culture medium containing ascorbic acid and FGF7 to produce primitive gut tube cells, and (c) culturing the primitive gut tube cells in a third culture medium containing retinoic acid and BMP2 or BMP4 to produce intestinal midgut endoderm cells.

Provided is a method for deriving and maintaining a midbrain-like organoid, comprising steps of (a) culturing pluripotent stem cells to obtain neuronal lineage embryoid bodies, (b) culturing the neuronal lineage embryoid bodies from (a) to obtain midbrain regionalized tissues, (c) embedding and culturing the midbrain regionalized tissues from (b) in an extracellular matrix to obtain developing neuroepithelial tissues, and (d) culturing the neuroepithelial tissues from (c) to obtain a midbrain-like organoid.

Provided is a mesenchymal stem cell (MSC) expressing miR-145-5p, miR-181b-5p and miR-214-3p, but not miR-127-3p or miR-299-5p. Also provided is a method for producing a MSC, comprising steps of (a) culturing a primitive mesoderm cell, which may be differentiated from a pluripotent stem cell, in a mesenchymal-colony forming medium comprising LiCl and FGF2, but excluding PDGF to form a mesenchymal colony and (b) culturing the mesenchymal colony adherently to produce the MSC.

Provided is a method for assessing the quality of stem cells in a sample comprising a step of measuring the expression level of at least one RNA in the sample.  The method may further comprise determining the quantity of unproductive (not-self-renewing) stem cells in the sample.

Provided is an in vitro method for differentiating human pluripotent stem cells into atrial cardiomyocytes, comprising steps of (a) contacting the pluripotent stem cells with a Wnt-signaling agonist and/or a BMP-signaling agonist for a period of about 6 - 54 hours, and (b) contacting the contacted cells in step (a) with a Wnt-signaling antagonist for a period of about 6 - 54 hours, wherein the cells are contacted with a retinoic acid-signaling agonist within the first 96 hours of steps (a) and (b) for a period of at least 6 hours.

Provided is a method for generating microglial cells from human pluripotent stem cells, comprising steps of (a) culturing the pluripotent stem cells under conditions that induce myeloid differentiation, leading to the generation of CD14+ and/or CX3CR1+ microglial progenitor cells, and (b) culturing the CD14+ and/or CX3CR1+ microglial progenitor cells in either (i) a first microglial differentiation medium comprising IL-34, or (ii) a second microglial differentiation medium comprising M-CSF.