Abstract: The present disclosure provides a model of human fibrolamellar hepatocellular carcinoma (FL-HCC) cells maintained as a transplantable tumor line in a host and a method to establish a transplantable human FL-HCC tumor line. Methods of ex vivo cultures of the FL-HCC are provided. Methods of diagnosing and treating FL-HCC tumors are also provided.

Abstract: Described are means, methods, and compositions useful for treatment of multiple sclerosis through the utilization of fibroblasts and/or derivatives thereof to concurrently stimulate regenerative processes while inducing a protolerogenic immune modulatory program. In certain embodiments, fibroblasts are selected for the concurrent properties of immune modulation and regeneration by enrichment for CD73 expressing fibroblasts. In particular embodiments, stimulation of regeneration implies activation of endogenous neural progenitor cells. In some embodiments, stimulation of regeneration implies induction of remyelination. The utilization of fibroblasts as a superior source for immune modulation, prevention of immune mediated pathology, and activation of T regulatory cells is provided within the context of multiple sclerosis.

Abstract: Disclosed herein are methods for generating mature cardiomyocytes and compositions including mature cardiomyocytes. Also disclosed herein are methods for enhancing maturation of quiescent cardiomyocytes and compositions including mature quiescent cardiomyocytes.

Abstract: A method of producing renal progenitor cells from pluripotent stem cells involves culturing pluripotent stem cells in a medium containing FGF2, BMP4, a GSK-3? inhibitor, and retinoic acid or a derivative thereof, culturing the resulting cells in a medium containing FGF2, a GSK-3? inhibitor, and BMP7, culturing the resulting cells in a medium containing FGF2, a GSK-3? inhibitor, BMP7, and a TGF? inhibitor, culturing the resulting cells in a medium containing FGF2, a GSK-3? inhibitor, BMP7, activin, and a ROCK (Rho-kinase) inhibitor, culturing the resulting cells in a medium containing retinoic acid or a derivative thereof, and FGF9, and culturing the resulting cells in a medium containing a GSK-3? inhibitor and FGF9, to induce renal progenitor cells from intermediate mesodermal cells.

Abstract: The object of the present invention is to provide a material for efficiently obtaining differentiated cells from pluripotent stem cells. That is, the present invention relates to a pluripotent stem cell differentiation-promoting agent containing, as an active ingredient, a ?-nicotinamide mononucleotide or a pharmacologically acceptable salt thereof, and a solvate thereof, and a method for differentiating pluripotent stem cells, including culturing pluripotent stern cells in a culture medium containing a ?-nicotinamide mononucleotide or a pharmacologically acceptable salt thereof, and a solvate thereof.

Abstract: Provided are a method for promoting the proliferation of pluripotent stem cells and a proliferation promoting composition used in the method. In one aspect, a composition for promoting the proliferation of pluripotent stem cells includes hemagglutinin or modified hemagglutinin. In another aspect, a method for promoting the proliferation of pluripotent stem cells includes culturing pluripotent stem cells in a culture medium to which the proliferation promoting composition of the present disclosure has been added.

Abstract: Disclosed herein are methods for the in vitro differentiation of a precursor cell into definitive endoderm, which may further be differentiated into a human colonic organoid (HCO), via modulation of signaling pathways. Further disclosed are HCOs and methods of using HCOs, which may be used, for example, for the HCOs may be used to determine the efficacy and/or toxicity of a potential therapeutic agent for a disease selected from colitis, colon cancer, polyposis syndromes, and/or irritable bowel syndrome.

Abstract: Disclosed are findings that: (a) induced pluripotent stem cells derived from aged donors (A-iPSC) show increased genomic instability, a defect in apoptosis, a defect in glucose metabolism, and a blunted DNA damage response are compared to those derived from young donors (Y-iPSC); and (b) inhibition of excessive glutathione-mediated H2O2 scavenging activity, found to be associated with A-iPSC and in turn inhibiting DNA damage response and apoptosis, substantially rescues these defects and reduces the oncogenic potential of A-iPSC. Supplementation of pluripotency factor ZSCAN10 (shown to be poorly activated in A-iPSC and to act upstream of glutathione involvement), e.g.

Abstract: An object of the present invention is to provide, for example, a more practical wound healing accelerator that more effectively accelerates wound healing. More specifically, a feature of the present invention is to provide, for example, a more practical wound healing accelerator that is easily obtained in a larger amount than that of peripheral blood platelet and has a better wound healing effect than that of peripheral blood platelet. The present invention employs a platelet-like cell population coexpressing one or more platelet surface markers and one or more mesenchymal cell surface markers. A wound healing accelerator containing the platelet-like cell population is a more practical wound healing accelerator that more effectively accelerates wound healing. The platelet-like cell population is easily obtained in a larger amount than that of peripheral blood platelet and has a better wound healing effect than that of peripheral blood platelet.

Abstract: The present invention relates to a hair growth-inducing ability enhancing effect of adipose stem cells obtained by performing treatment with udenafil and performing culture, and provides a composition for preventing or treating alopecia, or promoting hair growth, comprising, as an active ingredient, adipose stem cells obtained by performing treatment with udenafil and performing culture, IL-4, or IL-12B. In a case where a culture medium of adipose stem cells is treated with udenafil and cultured, IL-4 and IL-12B expression levels are increased in the adipose stem cells, and thus maturation of hair follicle cells is further promoted, so that hair growth can be induced. In addition, in a case where IL-4 and IL-12B, which are expressed in the adipose stem cells obtained by performing treatment with udenafil and performing culture, are applied to skin tissue, hair growth can be induced.

Abstract: Methods for differentiating human pluripotent stem cells to dorsal neuroectoderm progenitors and further to glial progenitor cells and oligodendrocyte progenitor cells (OPCs) using inhibitors of BMP signaling and MAPK/ERK signaling are provided. Also provided are cells and cellular compositions obtained by such methods, and uses of such cells. Further provided are methods and protocols for efficiently differentiating human pluripotent stem cells to OPCs in the absence of the ventralizing morphogen SHH or a SHH signaling activator. The methods of the present disclosure reproducibly produce dorsal neuroectoderm progenitor cells by day 7 of the differentiation process, glial progenitor cells by day 21 of the differentiation process and OPCs by day 42 of the differentiation process.

Abstract: A method for producing CD4/CD8 double-positive T cells, comprising the steps of: (1) culturing pluripotent stem cells in a medium to induce hematopoietic progenitor cells; and (2) culturing the hematopoietic progenitor cells obtained in the step (1) in a medium containing a p38 inhibitor and/or SDF-1 to induce CD4/CD8 double-positive T cells.

Abstract: The invention provides a method for the improved generation of genetically modified cells in vitro, in order to obtain a population of effector cells with immunotherapeutic activity and methods of using such cells in protocols for adoptive cell therapy. The invention further provides non-viral genetically modified cells, cell populations and cell cultures and the use thereof in the treatment or prevention of diseases and disorders.

Abstract: The invention features a substrate and compositions, kits, devices, and methods employing the substrate that produces an isolated population of cells from a general population. The isolated population is enriched for one or more target populations. Substrate is can be liquefied and allows recovery of unlabeled, viable, and functional cells.

Abstract: The present invention relates to culture media for oocytes and uses thereof. Specifically, media for culturing an oocyte in vitro are disclosed, wherein said media comprise granulocyte macrophage-colony stimulating factor (GM-CSF). The presence of GM-CSF in the media increases the maturation and/or developmental competence of the oocyte making it suitable for use in subsequent assisted reproductive technologies. Methods for increasing the maturation and/or developmental competence of an oocyte are also disclosed.

Abstract: The purpose of the present invention is to efficiently produce microglia from pluripotent stem cells. Provided is a method for producing microglia from pluripotent stem cells, comprising the following steps: (a) a step of co-culturing a pluripotent stem cell together with a feeder cell for 7 days or longer, and obtaining a blood progenitor cell; (b) a step of co-culturing the blood progenitor cell obtained in step (a) together with a feeder cell in the presence of IL-3 and/or GM-CSF, and obtaining an embryonic monocyte; and (c) a step of, in the presence of M-CSF, co-culturing the embryonic monocyte obtained in step (b) together with an astrocyte, or culturing the embryonic monocyte using an astrocyte supernatant.

Abstract: The present invention is directed to a method of generating multilineage potential cells by de-differentiation of somatic leukocytes in a mixed leukocyte suspension from a blood sample. The present invention is also directed to the use of the generated multilineage potential cells to treat conditions in humans and mammals.

Abstract: Culturing of organized 3D networks of neuronal cells is provided. Individual neuronal cells are encapsulated in gel beads. The gel beads are self-assembled into ordered structures in a bioreactor. Subsequent culturing of the cells in the bioreactor leads to the formation of an organized 3D network of the neuronal cells. Such structures have many applications, especially for as says of neuronal network function and/or structure.

Abstract: The present disclosure provides for methods and compositions for the modulation of CD5 in a subject. Also provided are methods of detecting and monitoring diseases, such as inflammatory and autoimmune diseases.

Abstract: An improvement to the GiWi protocol for differentiating human pluripotent cells to developmentally mature cardiomyocytes includes a step of activating innate immunity in mesoderm stage cells in the in vitro differentiation culture. When the mesoderm cells, which are precursors to cardiac progenitor cells, are primed by exposure to an activator of innate immunity, a population of cardiomyocytes is generated that is more developmentally mature than is generated in the GiWi protocol without the primed step. Also provided herein are in vitro ventricular conductive microtissues and isolated, in vitro populations of ventricular conduction system-like cells and methods for making the same.

Abstract: Methods are provided for the simple, fast, effective and safe directed differentiation of embryonic stem cells into the mature beta cells of enriched beta clusters, wherein the beta cells rapidly and reliably secrete insulin in response to glucose levels. The cells are useful transplant therapeutics for diabetic individuals. These cells can also be used for drug screening purposes to identify factors/chemicals capable of increasing beta cell functions, proliferation, survival, and resistance to immune assault.

Abstract: This invention provides a method for stably producing type II alveolar epithelial cells from pluripotent stem cells. Specifically, the invention relates to a method for producing type II alveolar epithelial cells from pluripotent stem cells comprising steps of: (1) culturing pluripotent stem cells in a medium containing activin A and a GSK3? inhibitor; (2) culturing the cells obtained in Step (1) in a medium containing a BMP inhibitor and a TGF? inhibitor; (3) culturing the cells obtained in Step (2) in a medium containing BMP4, retinoic acid, and a GSK3? inhibitor; (4) culturing the ventral anterior foregut cells obtained in Step (3) in a medium containing a GSK3? inhibitor, FGF10, KGF, and a NOTCH signal inhibitor; and (5) subjecting the alveolar epithelial progenitor cells obtained in Step (4) to three-dimensional culture in a medium containing a steroid drug, a cAMP derivative, a phosphodiesterase inhibitor, and KGF.

Abstract: Methods of producing stem cell conditioned media to treat mammalian injuries or insults. In at least one embodiment of a method for isolating non-endothelial adipocyte-depleted stromal cells of the present disclosure, the method comprises, comprising dissociating subcutaneous adipose tissue isolated from a mammal into a cell suspension, removing adipocytes from said cell suspension, resulting in a non-endothelial adipocyte-depleted cell suspension, and culturing the non-endothelial adipocyte-depleted cell suspension in a media containing growth factors VEGF, bFGF, EGF, and IGF, such that a mixed population of cells comprising a first population of further differentiated non-endothelial adipocyte-depleted CD34+/VE-cadherin? cells and a second population of further differentiated non-endothelial adipocyte-depleted CD34+/VE-cadherin+ cells are obtained and expanded.

Abstract: The invention provides a method for producing a substrate for supporting cells, including a humidification step of humidifying the periphery of a non-fluorine resin based substrate, and a UV irradiation step of irradiating the substrate with UV in an oxygen and/or ozone containing atmosphere during and/or after the humidification step. The invention also provides a substrate for supporting cells, which is a non-fluorine resin based substrate. The substrate has a cell supporting surface for supporting cells, containing a component capable of generating C7H5O+ molecules by beam irradiation of a time-of-flight secondary ion mass spectrometer, such that cells are supported on the cell-supporting surface.

Abstract: Compositions and methods for promoting adult mammalian cardiomyocytes processes and systems for enhancing cardiomyocyte regeneration are described. The invention relates to locally administering a therapeutic agent containing a modified messenger RNA for expressing a mutated serum response factor polypeptide and a modified messenger RNA for expressing a mutated YAP polypeptide into diseased heart muscle to promote cardiomyocyte proliferation and cardiac regeneration.

Abstract: The present invention describes a method for producing de novo papillae comprising the steps of a) providing isolated dermal papilla fibroblasts (DPF) from at least one dermal papilla (DP) from at least one hair follicle, b) providing isolated connective tissue sheath fibroblasts (CTSF) from at least one hair follicle and c) co-culturing the DPF with the CTSF under substantially non-adherent cell culture conditions to form spheroid cell aggregates.

Abstract: The invention provides culture platforms, cell media, and methods of differentiating pluripotent cells into hematopoietic cells. The invention further provides pluripotent stem cell-derived hematopoietic cells generated using the culture platforms and methods disclosed herein, which enable feed-free, monolayer culturing and in the absence of EB formation. Specifically, pluripotent stem cell-derived hematopoietic cell of this invention include, and not limited to, iHSC, definitive hemogenic endothelium, hematopoietic multipotent progenitors, T cell progenitors, NK cell progenitors, T cells, NK cells, NKT cells and B cells.

Abstract: Disclosed herein are methods, compositions, kits, and agents useful for inducing ? cell maturation, and isolated populations of SC-? cells for use in various applications, such as cell therapy.

Abstract: The present invention relates to methods for deriving human hematopoietic progenitors, primitive macrophages, and microglial cells from human pluripotent stem cells. In particular, provided herein are highly efficient and reproducible methods of obtaining human primitive macrophages and microglia from human pluripotent stem cells, where the primitive macrophages and microglia can be suitable for clinically relevant therapeutic applications.

Abstract: Disclosed herein are methods, compositions, kits, and agents useful for inducing ? cell maturation, and isolated populations of SC-? cells for use in various applications, such as cell therapy.

Abstract: Disclosed herein are methods, compositions, kits, and agents useful for inducing ? cell maturation, and isolated populations of SC-? cells for use in various applications, such as cell therapy.

Abstract: The present invention provides compositions and methods for reprogramming somatic cells using purified RNA preparations comprising single-strand mRNA encoding an iPS cell induction factor. The purified RNA preparations are preferably substantially free of RNA contaminant molecules that: i) would activate an immune response in the somatic cells, ii) would decrease expression of the single-stranded mRNA in the somatic cells, and/or iii) active RNA sensors in the somatic cells. In certain embodiments, the purified RNA preparations are substantially free of partial mRNAs, double-stranded RNAs, un-capped RNA molecules, and/or single-stranded run-on mRNAs.

Abstract: The present invention is directed towards methods of culturing non-keratinocyte epithelial cells, with the methods comprising culturing non-keratinocyte epithelial cells in the presence of feeder cells and a calcium-containing medium while inhibiting the activity of Rho kinase (ROCK) in the feeder cell, the non-keratinocyte epithelial cells or both during culturing.

Abstract: A method for assisting corneal severity identification, the method comprising obtaining a corneal configuration data set of a cornea to be examined by a tomography such as an optical coherence tomography; visualizing the corneal configuration data set of the cornea to be examined along with a number of pre-existing corneal configuration data sets of disorder corneas, disorder-suspect corneas and normal corneas obtained by the tomography using t-distributed Stochastic Neighbor Embedding in a two or three dimensional map, and judging corneal severity from the map.

Abstract: A delivery device for delivering an implantable leadless pacing device may include a catheter shaft a distal holding section for receiving the implantable leadless pacing device. In some cases, the delivery device may include a flow-sensing device to determine a pressure or flow-rate of a fluid within the distal holding section. Also included may be a handle assembly and a deployment mechanism to deploy the implantable leadless pacing device.

Abstract: The invention provides culture platforms, cell media, and methods of differentiating pluripotent cells into hematopoietic cells. The invention further provides pluripotent stem cell-derived hematopoietic cells generated using the culture platforms and methods disclosed herein, which enable feed-free, monolayer culturing and in the absence of EB formation. Specifically, pluripotent stem cell-derived hematopoietic cell of this invention include, and not limited to, iHSC, definitive hemogenic endothelium, hematopoietic multipotent progenitors, T cell progenitors, NK cell progenitors, T cells, NK cells, NKT cells and B cells.

Abstract: The invention provides cell culture conditions for culturing stem cells, including feeder-free conditions for generating and culturing human induced pluripotent stem cells (iPSCs). More particularly, the invention provides a culture platform that allows long-term culture of pluripotent cells in a feeder-free environment; reprogramming of cells in a feeder-free environment; single-cell dissociation of pluripotent cells; cell sorting of pluripotent cells; maintenance of an undifferentiated status; improved efficiency of reprogramming; and generation of a naïve pluripotent cell.

Abstract: Provided is a method of differentiating a pluripotent stem cell of mammalian origin into a desired cell type by predicting the direction of cell differentiation to be caused by induction of expression of a transcription factor. A human gene expression correlation matrix using human cells has been newly created, and further, it has been confirmed that human pluripotent stem cells can be differentiated into a desired cell type by introducing, into the human pluripotent stem cells, a transcription factor cocktail selected from the matrix.

Abstract: Compositions and processes for culturing human stem cells in vitro in an undifferentiated state are disclosed. In this regard, human embryonic stem cells proliferated and maintained their pluripotency when cultured on plates coated with recombinant laminin-10 (laminin-511).

Abstract: Described herein are methods relating to the differentiation of stem cells to more differentiated phenotypes, e.g. to terminally differentiated cell types and/or precursors thereof. In some embodiments, the methods relate to contacting the stem cells with differentiation factors and halting the cell cycle, thereby increasing the rate of differentiation.

Abstract: The present invention provides a method for producing a retinal pigment epithelial cell, including (1) a first step of subjecting pluripotent stem cells to floating culture in a serum-free medium to form an aggregate of pluripotent stem cells, (2) a second step of subjecting the aggregate formed in step (1) to floating culture in a serum-free medium or serum-containing medium each being free of a substance acting on the Sonic hedgehog signal transduction pathway and containing a substance acting on the BMP signal transduction pathway, thereby obtaining an aggregate containing retinal progenitor cells, and (3) a third step of subjecting the aggregate formed in step (2) to floating culture in a serum-free medium or serum-containing medium each being free of a substance acting on the Sonic hedgehog signal transduction pathway and a substance acting on the BMP signal transduction pathway and containing a substance acting on the Wnt signal pathway, thereby obtaining an aggregate containing retinal pigment epithel

Abstract: The present invention relates to the generation of neural cells from undifferentiated human embryonic stem cells. In particular it relates to directing the differentiation of human ES cells into neural progenitors and neural cells and the production of functioning neural cells and/or neural cells of a specific type. The invention also includes the use of these cells for the treatment of neurological conditions such as Parkinson's disease.

Abstract: A method for acquiring and producing high-purity renal progenitor cells from a renal progenitor cell population into which pluripotent stem cells are induced to differentiate, by identifying a cell surface antigen marker specific to renal progenitor cells. The disclosed method may include, for example, the steps of: (i) culturing the pluripotent stem cells under conditions that induce differentiation into renal progenitor cells; and (ii) sorting a cell population from the cells obtained at step (i), by using at least one cell surface marker selected from the group consisting of CD9(?), CD55(?), CD106(+), CD140a(+), CD140b(+), CD165(+), CD271(+) and CD326(?).

Abstract: An object of the present invention is to provide a pluripotent cell having high safety in application to regenerative medicine, and a method for production thereof. Another object of the present invention is to provide a pluripotent cell, particularly, having less concern for safety, such as a problem of cancerization of a cell, and the presence of bacteria in a cell, and a method for production thereof. According to the present invention, there is provided a method for producing a pluripotent cell from a somatic cell. The method comprises a step of inducing reprogramming of a somatic cell, by contacting the cell with a ribosome fraction derived from an organism. Further, according to the present invention, there is provided a composition for inducing reprogramming of a cell, comprising a ribosome fraction derived from an organism.

Abstract: The invention relates to the use of a homeoprotein of the bicoid family, in particular of the Otx family, for enhancing the survival of cultivated retinal ganglion neurones, and for preventing or treating ganglion neuron degeneration particularly occurring in glaucoma.

Abstract: This application relates to a method for differentiating somatic cells into multi-competent neural crest cells based on linked steps of chemically defined medium inductions. Neural crest cells are able to differentiate into numerous cell types like Schwann cells, chondrocytes, smooth muscle cells or adipocytes.

Abstract: The present invention relates to the field of stem cell biology, in particular the lineage specific differentiation of pluripotent or multipotent stem cells, which can include, but is not limited to, human embryonic stem cells (hESC) in addition to nonembryonic human induced pluripotent stem cells (hiPSC), somatic stem cells, stem cells from patients with a disease, or any other cell capable of lineage specific differentiation. Specifically described are methods to direct the lineage specific differentiation of hESC and/or hiPSC into floor plate midbrain progenitor cells and then further into large populations of midbrain fate FOXA2+LMX1A+TH+ dopamine (DA) neurons using novel culture conditions.

Abstract: Provided is a cell culture support, which is a support for attaching and culturing cells, and which includes: a fibrous web which is made by accumulating fibers of a biodegradable polymer and on which a plurality of pores are formed; and a plurality of beads formed on the fibers to secure spaces through which the cells penetrate into the fibrous web and grow therein.

Abstract: A temperature-responsive substrate having on its surface a layer containing at least one polymer, the at least one polymer being responsive to temperature and containing a fluorine-containing monomer-derived unit. Also disclosed is a polymer and composition for use in producing the substrate, as well as methods for producing, using and evaluating the substrate.

Abstract: Methods for producing hepatocytes from pluripotent human stem cells are disclosed herein. The stem cells are plated on a cell culture substrate comprising two laminins. The stem cells are then exposed to different cell culture mediums to induce differentiation. The resulting hepatocytes have higher metabolic capacity compared to hepatocytes cultured on different substrates.