Abstract: The present invention provides a prosthetic tissue or sheet capable of withstanding implantation operations, which can be used in actual operation and can be produced by culture. The present invention also provides a novel therapy which can substitute for cell therapy. Particularly, the present invention provides a method for producing a prosthetic tissue comprising a cell derived from a part other than myocardium and capable of withstanding implantation operation. The above-described objects of the present invention were partially achieved by finding that by culturing cells under specific culture conditions, the cells are unexpectedly organized into a tissue, and the resultant prosthetic tissue is capable of being detached from culture dishes. The present invention also provides a three-dimensional structure applicable to heart, comprising a cell derived from a part other than the myocardium of an adult.

Abstract: The present invention provides methods to promote the differentiation of pluripotent stem cells. In particular, the present invention provides a method to increase the expression of markers associated with the pancreatic endocrine lineage.

Abstract: The present invention relates to a method for producing platelets from mature megakaryocytes. More particularly, the invention relates to an ex vivo method for producing platelets, from mature megakaryocytes, said method comprising a step of subjecting a suspension of mature megakaryocytes to a flow having a minimal shear rate of 600 s?1 on a solid phase coated with Von Willebrand factor.

Abstract: The present invention relates to cells capable of expressing IDO, nucleic acid constructs for expression of IDO, cells comprising said constructs and methods of utilizing said cells in the treatment of diseases. In particular the present invention relates to cells which express IDO in the absence of exposure to IFN-gamma, and to their use in preparation and/or generation of immunomodulatory cells specific for an antigen.

Abstract: The disclosure provides methods for increasing genome stability of an embryonic stem (ES) cell or induced pluripotent stem (iPS) cell, increasing telomere length in an ES or iPS cell, or both, for example by contacting an ES or iPS cell with an agent that increases expression of Zscan4 in the cell. Methods for increasing genome stability or increasing telomere length in a population of ES or iPS cells are provided, for example by selecting Zscan4+ ES or iPS cells from the population of ES or iPS cells (which can include both Zscan4+ and Zscan4? ES or iPS cells). Therapeutic methods of using ES or iPS cells expressing Zscan4 are also provided. Further provided are methods of treating cancer by administering a Zscan4 polynucleotide or Zscan4 polypeptide. Also provided are methods of inducing differentiation of isolated ES or iPS cells into germ cells.

Abstract: Methods and small molecule compounds for stem cell differentiation are provided.

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: Methods and compositions for producing NKX6-1+ pancreatic progenitor cells and/or insulin producing cells from an endodermal cell population, the method comprising contacting the endodermal cell population with an EGF component, a Nicotinamide component and/or a Noggin component, optionally a combination of at least one EGF component and at least one nicotinamide component to induce the differentiation of at least one endodermal cell into a NKX6-1+ pancreatic progenitor cell, the combination optionally further comprising at least one Noggin component.

Abstract: The present invention provides an agent for promoting neuronal differentiation of neural stem cells, which contains a p38 inhibitor. In addition, the present invention provides a method of promoting neuronal differentiation of neural stem cells, which includes cultivating neural stem cells in the presence of a p38 inhibitor. Neural stem cells are gliogenic or neurogenic. The p38 inhibitor is a nucleic acid which hybridizes to DNA or mRNA encoding p38 under physiological conditions, thereby inhibiting the transcription and/or translation thereof, an expression vector of the nucleic acid, a low molecular p38 inhibitor and the like.

Abstract: The present invention relates to methods of using meso-1,2,3,4-tetrahydroxybutane for the maintenance and/or improvement of biological cell function and activity, and for the prevention of improper cell functioning or cell death, in vitro, ex vivo, and in vivo over time and/or during exposure to stress. Meso-1,2,3,4-tetrahydroxybutane can be used to promote cell survival and as a cell protection agent, to increase cell viability, and to improve conversion of progenitor or stem cells to mature cells, whether in vitro, in vivo, ex-vivo, or transplanted.

Abstract: A polyacrylamide hydrogel includes co-polymerized acrylamide, bisacrylamide and N-hydroxyethylacrylamide

Abstract: The present invention is of methods of establishing and propagating human embryonic stem cell lines using feeder cells-free, xeno-free culture systems and stem cells which are capable of being maintained in an undifferentiated, pluripotent and proliferative state in culture which is free of xeno contaminants and feeder cells.

Abstract: In one embodiment, a monocyte derived bone-forming cell population is provided. In one embodiment, the cell population comprises an isolated monocyte cell population treated with an effective dose of LL-37. In another embodiment, a method of producing a population of monocyte-derived bone-forming cells is provided. The method comprises obtaining a blood sample from a subject; isolating a population of monocytes from the blood sample; treating the isolated monocytes with an effective dose of LL-37; and culturing the LL-37 treated monocytes until they differentiate into the population of monocyte-derived bone-forming cells. In another embodiment, a method of treatment for a bone injury or bone disease is provided. The method comprises administering a therapeutically effective amount of a composition to a subject having the bone injury or disease, the composition comprising a population of monoosteophils.

Abstract: The slow kinetics and low efficiency of reprogramming methods to generate human induced pluripotent stem cells (iPSCs) impose major limitations on their utility in biomedical applications. Here we describe a chemical approach that dramatically improves (>200 fold) the efficiency of iPSC generation from human fibroblasts, within seven days of treatment. This will provide a basis for developing safer, more efficient, non-viral methods for reprogramming human somatic cells.

Abstract: Provided are methods and compositions useful for producing and propagating stem cells from fibroblasts.

Abstract: The present invention provides a method for improving iPS cell generation efficiency, which comprises a step of introducing a Myc variant having the following features: (1) having an activity to improve iPS cell generation efficiency which is comparative to, or greater than that of c-Myc; and (2) having a transformation activity which is lower than that of c-Myc; or a nucleic acid encoding the variant, in a nuclear reprogramming step. Also, the present invention provides a method for preparing iPS cells, which comprises a step of introducing the above Myc variant or a nucleic acid encoding the variant and a combination of nuclear reprogramming factors into somatic cells. Moreover, the present invention provides iPS cells comprising the nucleic acid encoding the Myc variant which can be obtained by the above method, and a method for preparing somatic cells which comprises inducing differentiation of the iPS cells.

Abstract: Methods and compositions for directing adipose-derived stromal cells cultivated in vitro to differentiate into cells of the chondrocyte lineage are disclosed. The invention further provides a variety of chondroinductive agents which can be used singly or in combination with other nutrient components to induce chondrogenesis in adipose-derived stromal cells either in cultivating monolayers or in a biocompatible lattice or matrix in a three-dimensional configuration. Use of the differentiated chondrocytes for the therapeutic treatment of a number of human conditions and diseases including repair of cartilage in vivo is disclosed.

Abstract: A 3D in vitro bi-phasic cartilage-bone organoid includes a layer of an artificial cartilage tissue, and a layer of an artificial bone tissue comprising a structure-giving scaffold and a bone marrow structure. The layer of the artificial cartilage tissue contacts at least one surface of the layer of the artificial bone tissue.

Abstract: This invention provides disc stem cells, processes for obtaining and culturing disc stein cells, and methods for repairing damaged or diseased disc tissue comprising the use of the disc stem cells of the invention.

Abstract: The present invention relates to a method for inducing and/or promoting osteogenic differentiation using extracellular vesicles and the use thereof.

Abstract: A composition of a female germinal cell (egg) extract of pluricellular organisms in M-phase of the cell cycle, the extract being used for a mitotic remodeling of chromosomes of donor cells of pluricellular organisms, wherein the mitotic remodeling confers to the nucleus of the donor cells the ability to adapt themselves to the early embryonic development, in particular to the replication phases, in order to carry out the embryonic development or to obtain stem cells.

Abstract: The invention relates to material compositions comprising adult stem cells obtained from exocrine gland tissue and a supporting matrix having the shape of a thread structure and/or of a net. The supporting matrix preferably consists of a plastic material which is physiologically acceptable and degradable in the body. The material compositions of the invention are in particular suited for use in regenerative medicine, e.g. for regeneration of injured or damaged myocard tissue.

Abstract: This invention relates to novel ?-galactosidases for the enzymatic removal of the immunodominant monosaccharides on blood products and tissues. Specifically this invention provides a novel family of ?3 glycosidases, used for the enzymatic removal of type B antigens from blood group B and AB reactive blood products, and the Galili antigen from non-human animal tissues, thereby converting these to non-immunogenic cells and tissues suitable for transplantation.

Abstract: An object of the present invention is to provide a method for inducing the differentiation of erythropoietin-producing cells from human pluripotent stem cells. The above object is achieved by providing a method for inducing the differentiation of erythropoietin-producing cells from human pluripotent stem cells using a medium containing a specific growth factor and a specific compound.

Abstract: The present invention relates to a method of deriving an induced neural stem cell (iNCS) by nuclear reprogramming of a somatic cell, wherein the method comprises a step of contacting the somatic cell with Oct4 protein or a functionally equivalent analogue, variant or fragment thereof for a limited time period, as well as an induced neural stem cell obtained by this method.

Abstract: Described herein are methods for enhancing the nuclear reprogramming of somatic cells to become induced pluripotent stem cells. In particular, the methods disclosed herein involve the use of damage-associated molecular pattern molecules (DAMP). In certain embodiments the DAMPs are aluminum compositions such as aluminum hydroxide. Such DAMPs have unexpectedly and surprisingly been found to enhance the nuclear reprogramming efficiency of the reprogramming factors commonly used to induce somatic cells to become induced pluripotent stem cells. Accordingly, this disclosure describes methods of nuclear reprogramming as well as cells obtained from such methods along with therapeutic methods for using such cells for the treatment of disease amendable to treatment by stem cell therapy; as well as kits for such uses.

Abstract: Provided is a novel ligand for integrin ?9?1 consisting of a peptide having the following amino acid sequence: (A) EDDMMEVPY (SEQ ID NO: 1) or (B) an amino acid sequence the same as the amino acid sequence represented by SEQ ID NO: 1 except for having deletion, substitution or addition of 1 to 3 amino acids. The novel ligand for integrin ?9?1 has a higher binding affinity than those of tenascin-C and osteodontin, which are known ligands for integrin ?9?1.

Abstract: A bed of microbeads is used as a foundation for reconstructing a three-dimensional osteocyte network by culturing osteocytes within the bed. The osteocytes are cultured such that they form a network among the microbeads that is capable of simulating the osteocyte network of natural bone. The osteocytes are cultured in a microfluidic device adapted for the purpose.

Abstract: The present invention is a method and kits for generating a homogenous population of hematopoietic progenitor cells capable of differentiating into a hematopoietic cell lineage. Whereas the combination of Homeobox-B8 protein and FMS-like tyrosine kinase 3 ligand generate cells with the potential to differentiate into different myeloid and lymphoid cell types, Homeobox-A7 protein and erythropoietin generate cells with the potential to differentiate into erythropoietic or thrombopoietic cell types.

Abstract: A method of treating a cellular proliferative disorder in a subject by obtaining from a subject a bodily fluid sample containing a plurality of cells, incubating the sample with EDTA or heparin in a container until the sample is separated into an upper layer and a lower layer, collecting the upper layer, isolating from the upper layer a population of somatic stem cells that are 0.3-6.0 micrometers in size, differentiating the somatic stem cells to dendritic cells in a medium containing GCSF, SCF, EGF, PDGF, bFGF, and IL-3, purifying the dendritic cells, contacting the dendritic cells thus purified with a cancer antigen, and administrating an effective amount of the dendritic cells presenting the cancer antigen to a subject in need thereof.

Abstract: The present invention provides methods for inducing differentiation of an embryonic stem cell into a motor neuron using a motoneuronotrophic factor (MNTF) or its peptide analogs. The present invention further provides a method for isolating a population of stem cell derived motor neurons and a population of cells comprising the differentiated neural cells. Additionally, the present invention is directed to a method of enhancing the survival of the differentiated neural cells in long term cell cultures. Finally, the present invention provides compositions containing MNTF or its peptide analogs for therapeutic use in conjunction with stem cells.

Abstract: The present invention provides a method of generating definitive endoderm, mesoderm, or ectoderm cells. The method includes culturing embryonic stem cells, parthenogenetic cells, or induced pluripotent stem cells in the presence of a demethylation agent, a histone deacetylase inhibitor, or a combination thereof, and thereafter, culturing the stem cells in the absence of the agent or combination of agents, to produce definitive endoderm cells, mesoderm, or ectoderm cells.

Abstract: The present invention is based on the discovery of polyclonal IgG's ability to promote Schwann cell maturation, differentiation, and myelin production. Methods for treating non-idiopathic, demyelinating peripheral neuropathies in mammals, where the neuropathy is not immune-mediated or infection-mediated, through the administration of polyclonal IgG are provided. Types of demyelinating peripheral neuropathies treatable with the present invention include peripheral nerve trauma and toxin-induced peripheral neuropathies. Alternatively, a composition of polyclonal IgGs can be applied directly to a peripheral nerve cell to induce maturation, differentiation into a myelinating state, and myelin expression or promote cell survival.

Abstract: Provided are ex vivo and in vivo methods of expanding renewable stem cells using agents capable of down-regulating Sir2 protein activity and/or expression, expanded populations of renewable stem cells, and uses thereof.

Abstract: Provided are compounds of formula (I) and/or salts thereof, of the class of substituted pyridines and pyrimidines, useful for inducing cardiomyogenesis, a process for producing cardiomyocyte-like cells from mammalian cells by culturing mammalian cells in the presence of the compound of formula (I), the pharmaceutical use of compounds of formula (I) for producing cardiomyocyte-like cells from omnipotent, pluripotent, or lineage committed mammalian cells, and the use of thus produced cardiomyocyte-like cells for treating disorders associated with impaired function of the heart.

Abstract: The present invention is directed to methods and substrates for promoting the differentiation of neural stem cells to neurons.

Abstract: The invention provides compositions and methods for treating or preventing hearing loss in a subject. The method comprises administering to the subject in need thereof, at least Myc or an agent that increases the expression of Myc in an inner ear organ, or associated neural structures, of the subject so as to treat or prevent the hearing loss.

Abstract: The present invention relates to new therapeutic and diagnostic uses of soluable neuregulin-1 isoforms and polypeptides, particularly neurological disorders.

Abstract: Disclosed is a therapeutic composition comprising human embryonic stem cell-derived micro vesicles, and methods of their use, including treatment of eye pathologies and of obtaining retinal neural cells and retinal stem cells.

Abstract: The present invention provides for the generation and maintenance of pluripotent cells by culturing the cells in the presence of an ALK5 inhibitor.

Abstract: This invention relates to methods of producing hair folliclesin vitro, compositions for producing hair follicles in vitro, in vitro produced hair follicles, methods of providing an in vitro produced hair shaft at an interfollicular or intrafollicular site, methods of treating hair loss by providing an in vitro produced hair shaft at an interfollicular or intrafollicular site and assays for studying the effect of test agents on hair biology. The invention also provides the similar methods and products which are, or use, immature follicles (“defined herein as proto-hairs”). The invention provides a method for in vitro production of a hair follicle or a proto-hair comprising co-culturing dermal papilla cells with keratinocytes, and optionally with melanocytes.

Abstract: Provided herein are methods of producing natural killer cells using a two-step expansion and differentiation method. Also provided herein are methods of suppressing tumor cell proliferation, of treating individuals having cancer or a viral infection, comprising administering the NK cells produced by the method to an individual having the cancer or viral infection.

Abstract: A method of treating an individual (i) having abnormal bone; or (ii) afflicted with a disease or disorder related to normal or abnormal FGF receptors or a skeletal disorder; or (iii) having dysplasic bone. The method includes administering to the individual a pharmaceutical composition comprising a therapeutically effective amount of a fibroblast growth factor 9 (FGF-9) variant comprising at least one amino acid substitution in the beta 8-beta 9 loop, wherein said FGF-9 variant incorporates one of the amino acid sequences set forth in SEQ ID NO: 11, 13, 14, 15, 16 or 17.

Abstract: The invention relates to progenitor cells of mesodermal lineage and their use in therapy.

Abstract: The invention is directed to methods for reprogramming somatic cells to a less differentiated state. In particular, the invention is directed to methods for reprogramming amnion epithelial cells (AEC) including amnion-derived cells (ADC) and Amnion-derived Multipotent Progenitor cells (AMP cells) to a less differentiated state. The invention is further directed to compositions comprising reprogrammed AEC, ADC and AMP cells, and uses thereof.

Abstract: According to the present invention, when nicotinamide is added in a culture process for producing pluripotent stem cells from human differentiated cells, it can increase the efficiency of reprogramming and can significantly reduce the time required for induction of reprogramming. It was verified that nicotinamide inhibits the induction of senescence and oxidative stress in the reprogramming process and increases cell proliferation and mitochondrial activity to effectively improve culture conditions for induction of reprogramming. Particularly, the present invention will contribute to optimizing a process of producing induced pluripotent stem cells from a small amount of patient-specific somatic cells obtained from various sources, and thus it will significantly improve a process of developing clinically applicable personalized stem cell therapy agents and new drugs and will facilitate the practical application of these agents and drugs.

Abstract: The present invention relates to a method for preparing a cytotoxic lymphocyte characterized in that the method comprises the step of carrying out at least one of induction, maintenance and expansion of a cytotoxic lymphocyte in the presence of fibronectin, a fragment thereof or a mixture thereof.

Abstract: Provided are: a method for producing an immortalized human erythroid progenitor cell line, enabling efficient and stable production of enucleated red blood cells; and a method for producing human enucleated red blood cells from a human erythroid progenitor cell line obtained by the aforementioned production method. An expression cassette capable of inducing expression of HPV-E6/E7 genes in the presence of DOX was introduced into the genomic DNA of blood stem cells. Then, the blood stem cells were cultured in the presence of DOX and a blood growth factor. Thereby, immortalized cell lines of human erythroid progenitor cells were established. Further, it was revealed that culturing the cell lines under a condition where the expression of the HPV-E6/E7 genes was not induced enabled differentiation induction into enucleated red blood cells at a high ratio.

Abstract: A method of preparing a reprogramming induced pluripotent stem cell from a human-derived somatic cell using a fusion protein in which a reprogramming inducing factor and cell permeable peptide (CPP) are fused, and a fusion protein in which a reprogramming inducing factor and a cell permeable peptide are fused are disclosed. According to the present invention, the induced pluripotent stem cell having high efficiency and high stability can be prepared by maximizing the effect of the reprogramming inducing transcription factor beyond the existing viral peptide transporter, in inducing the reprogramming of the somatic cell.

Abstract: Bone cages are disclosed including devices for biocompatible implantation. The structures of bone are useful for providing living cells and tissues as well as biologically active molecules to subjects.