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Provided is a method for producing an intestinal organoid from pluripotent stem cells, comprising steps of (1) differentiating the pluripotent stem cells into endoderm-like cells, then into intestinal stem cell-like cells, (2) culturing the intestinal stem cell-like cells obtained in (1) to form a spheroid, and (3) differentiating the spheroid formed in (2) to form an intestinal organoid in the presence of EGF, a BMP inhibitor, a Wnt signal activator, a MEK1/2 inhibitor, a DNA methylation inhibitor, a TGFβ receptor inhibitor, and a γ-secretase inhibitor.

Provided is a method for producing an osteoblast cluster from human iPS cells (hiPSCs), comprising steps of (1) inducing formation of embryoid bodies (EBs) by a non-adhesive culture of hiPSCs, (2) inducing differentiation into mesodermal cells by a non-adhesive culture of EBs obtained in (1), and (3) inducing differentiation into osteoblasts by a non-adhesive culture of the mesodermal cells obtained in (2).

Provided is a method for efficiently producing dopaminergic neurons within a short period of time from pluripotent stem cells, comprising steps of (1) culturing pluripotent stem cells in the presence of a TGF-β family inhibitor, a GSK3β inhibitor and a BMP inhibitor, (2) suspension-culturing the cells obtained in (1) in the presence of a TGF-β family inhibitor, a GSK3β inhibitor, FGF8 and a hedgehog signal agonist under normal oxygen partial pressure so as to form neurospheres, and (3) collecting cells constituting the neurospheres and inducing the differentiation thereof into dopaminergic neurons.

Provided is a method for producing an integrated human forebrain structure in vitro, comprising steps of inducing a neural fate in a pluripotent stem cell (e.g. an iPS cell) suspension culture to provide a spheroid of neural progenitor cells, then (i) differentiating the neural progenitor cells in a spheroid into cortical spheroids (hCS) and (ii) differentiating the neural progenitor cells in a spheroid into subpallial spheroids (hSS) as well, and culturing the hCS and hSS under conditions permissive for cell fusion in neural medium in the absence of growth factors; wherein an integrated forebrain structure is produced comprising interacting GABAergic and glutamatergic neurons.

The present invention provides a method for producing NKX6.1(+) pancreatic progenitor cells from NKX6.1(-) cells which may be derived from human pluripotent stem cells, chalacterized by a step of culturing the NKX6.1(-) cells in the presence of a factor having an inhibitory activity to cyclin-dependent kinase 8 and/or cyclin-dependent kinase 19 (CDK8/19).

The present invention provides a method for producing retinal pigment epithelial cells in a more efficient and simple manner comprising steps of; (1) culturing pluripotent stem cells for a period that does not exceed 30 days by using a medium containing at least one type of substance selected from a group consisting of FGF receptor inhibitors and MEK inhibitors, and (2) forming the retinal pigment epithelial cells by culturing the cells obtained in step (1) by using a medium containing at least one type of substance selected from a group consisting of Rho-signaling-pathway inhibitors and apoptosis inhibitors.

Provided is a method for differentiating pluripotent stem cells in a cell population expressing one or more neural stem cell marker(s) into a cell population comprising at least about 10% differentiated cells expressing one or more glial competent cell marker(s), characterized by a step of promoting nuclear factor I-A (NFIA) signaling in the first cell population.

Provided is a method for producing iPS cells having a γδ-TCR reconstituted gene. The method comprises steps of (a) stimulating blood cells by bisphosphonate and one or more interleukins selected from IL-2, IL-15, and IL-23, and then (b) reprogramming the blood cells stimulated in (a) using Sendai virus vectors to produce iPS cells.

The present invention provides a method for producing steroidogenic cells, comprising a step of treating intermediate mesoderm cells, which may be differentiated from iPS cells, with one ore more compound(s) selected from a group consisting of a dopamine D1 receptor agonist, ACTH, and dopamine to induce differentiation into steroidogenic cells.

The present invention provides a pluripotent stem cell-derived endodermal cell mass in which the content of undifferentiated cells is reduced and which contains endodermal cells capable of producing somatic cells that are suitable for a cell therapy preparation. The endodermal cell mass according to this invention is characterized by the relative expression levels of certain genes to that of OAZ1 (ornithine decarboxylase antizyme 1) gene.

The present invention provides an agent for accelerating growth of stem cells (e.g. ESCs or iPSCs) while maintaining differentiation potentials, which contains, as active ingredients, β-nicotinamide mononucleotide or a pharmaceutically acceptable salt thereof, and a solvate thereof.

Provided is a method of generating photoreceptor cells, comprising a step of culturing stem cells (e.g. ESCs or iPSCs) in a medium containing nicotinamide.

The present disclosure illustrates a system and method for combinational and multiplexed viral transduction that significantly decreases time and cost of analyzing effects of delivered genes to cells. One of the examples is a method for isolating and producing iPSCs, comprising steps of detecting a plurality of cell surface markers expressed on the surface of the iPSCs, mapping a plurality of candidate binding agents to the markers by a processor of a computer device, and separating the iPSCs by using the binding agent.

Provided is a method for evaluating cell differentiation status comprising a step of measuring miRNA in miR302/367 cluster in a liquid phase fraction of a cell culture during and/or after inducing differentiation of pluripotent stem cells.

Present invention provides a method for efficiently inducing differentiation into insulin-producing cells from pluripotent stem cells, which is based on inventors' finding that a compound having an ABL1 tyrosine kinase inhibitory effect serves to promote the induction of such differentiation.

Provided is a method for producing regulatory T cells for inducing immunotolerance in a subject, comprising a step of co-culturing regulatory T cells obtained from the subject with iPS-cell-derived dendritic cells which are, in one embodiment, sensitized with a specific target antigen in vitro.

Provided is a method for generating a hypo-immunogenic pluripotent stem cell comprising steps of (a) eliminating the activity of both alleles of B2M gene in an iPS cell, (b) eliminating the activity of both alleles of CIITA gene in said iPS cell, and (c) increasing the expression of CD47 in said iPS cell.

Provided is a compound represented by a formula shown in the specification which exhibits an inhibiting effect to cancer cell sphere formation and is useful as an agent for removing iPS cells inside cell sphere.

Provided is an undifferentiated stem cell removal agent which contains at least one component selected from the group consisting of the followings; (a) cells that can specifically inhibit the propagation of glypican-3-expressing cells; (b) compounds that can specifically inhibit the propagation of glypican-3-expressing cells; (c) cells that can induce a specific immune response to glypican-3-expressing cells; and (d) compounds that can induce a specific immune response to glypican-3-expressing cells.

Provided are a method for promoting proliferation of pluripotent stem cells and a proliferation-promoting composition. In one embodiment, said proliferation-promoting composition comprises hemagglutinin or a mutant thereof.

The present invention relates to a method for producing endothelial cells comprising steps of; (a) inducing a mesoblastic cell mass containing endothelial progenitor cells from pluripotent stem cells without forming embryoid bodies, and (b) culturing the mesoblastic cell mass containing endothelial progenitor cells in the presence of RepSox (CAS No. 446859-33-2).

Provided is a method for preparing amnion-like tissue comprising: a step of culturing stem cells (e.g. iPS cells) on a solid surface such as glass or polydimethylsiloxane (PDMS) coated with a gel matrix.

Provided is a method for inducing differentiation of stem cells into glucose-sensing insulin-secreting pancreatic beta cells by transfecting a first combination of mRNAs (comprising FoxA2 or Sox 17), a second combination of mRNAs (comprising PDX1, Hlxb9, Ptf1a, HNF1a/b, or Sox9), and then a third combination of mRNAs (comprising PDX1, NKX6.1, NKX2.2, Pax6, Pax4, Hlxb9, or Ngn3) in the courses of differentiation.

Provided is a method for inducing differentiation of stem cells into hepatocytes by transfecting a first combination of mRNAs (comprising FoxA2 or Sox 17), a second combination of mRNAs (comprising Tbx3 or Hex), and then a third combination of mRNAs (comprising HNF4a or HNF1a) in the courses of the differentiation.

Provided is a method for preparing a Leydig-like cell from a human pluripotent stem cell (PSC) by overexpressing NR5A1 gene in the PSC.

Provided is a method for producing biliary epithelial progenitor cells comprising a step of culturing hepatoblasts which may be induced from human pluripotent stem cells, in a medium containing TGFβ and EGF. Further provided is a method for constructing a 3D duct-like structure of biliary epithelial progenitor cells comprising a step of culturing hepatoblasts or biliary epithelial progenitor cells in a medium containing HGF, EGF, a Notch inhibitor and a GSK3 inhibitor in the presence of a 3D scaffold.

Provided is a method for inducing differentiation of pluripotent stem cells (PSCs) into somatic cells using a medium containing a heparin binding growth factor, wherein the method conprises a step of contacting the PSCs with a conjugate comprising a laminin E8 fragment linked with a fragment containing a growth factor-binding site of heparan sulfate proteoglycan.

Provided is a method for producing HLA homozygous immune cells comprising steps of (a) obtaining iPSCs, wherein the iPSCs are reprogrammed from a population of HLA homozygous blood cells, (b) differentiating the iPSCs to hematopoietic precursor cells (HPCs), and (c) culturing the HPCs under conditions to promote immune cell differentiation, thereby producing HLA homozygous immune cells.

Provided is a method for producing a population of primed cardiac progenitors from pluripotent stem cells, comprising steps of (i) activating Wnt/β-catenin signaling in cultured pluripotent stem cells to obtain a first cell population, (ii) culturing the first cell population until cardiac mesoderm cells are present in the cell population, and (iii) inhibiting Wnt/β-catenin signaling in the cardiac mesoderm cells in the presence of an activator of innate immunity until a second cell population comprising primed cardiac progenitors is produced. As a preferred embodiment, the said activator of innate immunity is a TLR 3 ligand or a NF-κB activator.

Provided is a Paramyxoviridae viral vector for reprogramming somatic cells into iPS cells, wherein the said vector comprises nucleic acids encoding a plurality of reprogramming factors and a nucleic acid sequence targeted by a microRNA associated with pluripotency.