Abstract: Compounds containing nucleic acid bases or their precursors modified by enrichment at specific sites with heavy stable isotopes of elements naturally present at those sites in minute amount are useful for the treatment of diseases characterized by altered gene expression and altered pattern of epigenomic control. These compounds, when used as nutrients or in other medicinal application methods, can alter the DNA methylation pattern in a simple way through the well-understood mechanism of kinetic isotope effect (KIE). This effect could also be useful for modifying methylation kinetics in stem cell technology, cloning and as disease therapeutics.

Abstract: The present invention relates to methods for culturing human retinal progenitor cells under low oxygen conditions to allow the cells to retain the ability to differentiate into photoreceptors following transplantation. The described methods provide cells that can treat a number of ocular diseases, including retinitis pigmentosa and age-related macular degeneration.

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: Certain embodiments disclosed herein are directed to a method of producing pancreatic cells or pancreatic cell precursors by exposing human embryonic stem cells to an effective amount of at least one compound listed in Table I to differentiate the human embryonic stem cells into the pancreatic cells or the pancreatic cell precursors. Kits and pancreatic cell lines produced using the methods are also described.

Abstract: A method of ex-vivo increasing insulin content in progenitor cells which express SLUG is provided. The method comprises downregulating an amount or activity of SLUG in the progenitor cells. Cell populations generated thereby and uses thereof are also provided.

Abstract: Synthetic surfaces suitable for culturing stem cell derived cardiomyocytes contain acrylate polymers formed from one or more acrylate monomers. The acrylate surfaces, in many cases, are suitable for culturing stem cell derived cardiomyocytes in chemically defined media.

Abstract: Disclosed herein is a reprogrammed endothelial progenitor cell, said cell comprises a bone marrow-derived cell expressing the CD34+ marker and at least one cardiomyocyte-specific gene, as well as methods for preparing and using the same for cardiac regenerative medicine.

Abstract: Methods are provided for producing a cardiomyocyte population from a mammalian pluripotent stem cell population. Aspects of the methods include using a Wnt signaling agonist and antagonist, each in minimal media, to modulate Wnt signaling. Also provided are kits for practicing the methods described herein.

Abstract: Simplified methods and compositions for directed differentiation of human pluripotent stem cells into neural stem cells are described. Methods and compositions for deriving neural stem cells from human pluripotent stem cells under defined, xeno-free conditions are also described.

Abstract: Provided are a composition for stimulating differentiation of MSCs into osteoblasts, which includes cryptotanshinone, and an osteogenesis stimulator including cryptotanshinone and MSCs. When the cryptotanshinone is treated to the MSCs, the differentiation into osteoblasts is stimulated, and thus osteogenesis of a patient may be stimulated by directly transplanting the differentiation-induced MSCs to the patient. Accordingly, the composition or osteogenesis stimulator may be used to treat patients having disability requiring stimulation of osteogenesis such as osteoporosis, bone fracture, bone grafting including alveolar bone grafting for implant placement, or other bone defects.

Abstract: Methods of producing populations of predominantly astrocytes, neurons or oligodendrocytes are provided. In addition, methods of treating mammals having astroglial tumors, oligodendrocyte tumors, or neuronal tumors are provided.

Abstract: Nucleotide sequences encoding novel splice variants of FOXP1, proteins encoded by the novel splice variants and antibodies thereto are disclosed. In addition, methods are described for maintaining a population of homogenous self-renewing and pluripotent stem cells, suppressing stem cell differentiation, and reprogramming somatic cells into pluripotent stem cells comprising the use of the novel splice variants. Also disclosed are modulators of alternative splicing such as MBNL1 and MBNL2 and methods and uses thereof for promoting pluripotency.

Abstract: The present invention relates to methods of constructing an integrated artificial immune system that comprises appropriate in vitro cellular and tissue constructs or their equivalents to mimic the normal tissues that interact with vaccines in mammals. The artificial immune system can be used to test the efficacy of vaccine candidates in vitro and thus, is useful to accelerate vaccine development and testing drug and chemical interaction with the immune system.

Abstract: The present invention is based, at least in part, on novel, unimolecular STAT3 oligonucleotide decoys exhibiting increased in vivo stability as compared to previously known decoys which are effective in inhibiting STAT3 when administered systemically. The invention is also based on pharmaceutical compositions comprising these unimolecular decoys, and methods for using these decoys in the treatment of cancer.

Abstract: An object of the present invention is to provide a method of promoting polyploidization of megakaryocytes and thereby producing highly polyploidized megakaryocytes, a method of efficiently producing platelets from polyploidized megakaryocytes, and the like. The present invention provides a method of producing polyploidized megakaryocytes comprising a step of forcing expression of an apoptosis suppressor gene in megakaryocytes before polyploidization and culturing the resulting cells.

Abstract: The present invention relates to a composition for promoting differentiation of pluripotent stem cells into cardiac muscle cells, and a method for inducing differentiation of pluripotent stem cells into cardiac muscle cells and a method for preparing cardiac muscle cells

Abstract: This invention relates to the production of populations of Smooth Muscle Cells (SMCs) of specific embryonic lineages, such as neuroectodermal and mesodermal SMCs. Pluripotent stem cells are cultured in one or more lineage induction media to produce progenitor cells of a defined embryonic lineage, which are then cultured in an SMC induction medium to produce a population of SMCs of the embryonic lineage. Populations of SMCs of defined lineages may be useful, for example, in in accurately modelling vascular disease.

Abstract: A major object of the present invention is to provide a method for inducing cell differentiation into corneal epithelial stem cells and/or corneal epithelial cells, for the easy production of a corneal epithelial cell sheet having superior safety in view of the possibility of vascularization and the like occurring. A method for inducing differentiation of a pluripotent stem cell into a corneal epithelial stem cell and/or a corneal epithelial cell, the method comprising the step of culturing a pluripotent stem cell in the presence of a stromal cell or an amnion-derived factor.

Abstract: The invention relates to a method for reprogramming target cells to multipotent progenitor cells capable of differentiating into muscular, skeletal or dermal cell lines. In particular, the invention relates to an ex vivo method for preparing induced presomitic mesoderm (iPSM) cells, said method comprising the steps of: a) providing target cells to be reprogrammed, and, b) culturing said target cells under appropriate conditions for reprogramming said target cells into iPSM cells, wherein said appropriate conditions comprises increasing expression of at least one T-Box transcription factor in said target cells. The invention further relates to the use of said iPSM cells, for example, for regenerating skeletal, muscle, dermal and cartilage tissues.

Abstract: Provided are a modified laminin having a cell-growth regulatory molecule bound to at least one site selected from the ? chain N-terminus, the ? chain C-terminus, the ? chain N-terminus and the ? chain N-terminus of laminin or a heterotrimeric laminin fragment, a method for culturing cells in the presence of the modified laminin, a method for establishing iPS cells in the presence of the modified laminin, and a culture substrate coated with the modified laminin. Human stem cells cultured in a xeno-free environment with the use of the modified laminin of the present invention can be provided as highly safe human stem cells applicable to regenerative medicine.

Abstract: Compositions and methods related to Wnt signaling regulation by Dickkopf (Dkk) polypeptides and Wnt-related diseases are disclosed. For example, compounds that bind a Dkk or LRP polypeptide are disclosed. Compounds that disrupt binding of a Dkk polypeptide to an LRP polypeptide are also disclosed. Methods for using the described compounds and compositions are also disclosed.

Abstract: We disclose a particle comprising a matrix coated thereon and having a positive charge, the particle being of a size to allow aggregation of primate or human stem cells attached thereto. The particle may comprise a substantially elongate, cylindrical or rod shaped particle having a longest dimension of between 50 ?m and 400 ?m, such as about 200 ?m. It may have a cross sectional dimension of between 20 ?m and 30 ?m. The particle may comprise a substantially compact or spherical shaped particle having a size of between about 20 ?m and about 120 ?m, for example about 65 ?m. We also disclose a method of propagating primate or human stem cells, the method comprising: providing first and second primate or human stem cells attached to first and second respective particles, allowing the first primate or human stem cell to contact the second primate or human stem cell to form an aggregate of cells and culturing the aggregate to propagate the primate or human stem cells for at least one passage.

Abstract: The invention provides methods, uses, kits and compositions comprising a therapeutically effective amount of the microRNA miR-223 for treating myelogenous leukemia in a subject in need of such treatment. The invention further comprises methods encompassing the use of miR-223 for promoting the differentiation of a leukemia stem cell that is resistant to a differentiating agent, and a method of screening for candidate compounds capable of treating a myeloid leukemia by comparison of the therapeutic activity of the candidate compound with the therapeutic activity of miR-233.

Abstract: The present invention relates to a non-genetic, detergent-free, bacteria-free method for reprogramming a eukaryotic cell, in particular for obtaining induced pluripotent stem cells (iPS), by using engineered microvesicles carrying at least one reprogramming transcription factor, wherein said engineered microvesicles are virus-free.

Abstract: In general, iPS cells are produced by delivery of stem cell-associated genes into adult somatic cells (e.g., fibroblasts). Described herein are methods for enhancing the efficiency and rate of induced pluripotent stem cell production by treating somatic cells with a transforming growth factor-beta receptor (TGF?R) inhibitor. Also described herein are iPS cell compositions made according to the methods described herein and iPS cell compositions comprising an iPS cell in an admixture with a TGF?R inhibitor. Further described herein are kits for producing iPS cells using a TGF?R inhibitor.

Abstract: A technique is needed which can amplify NK cells in vitro and prepare optimum number of NK cells for the adoptive immunotherapy. A method for amplifying NK cells is provided which comprises steps of: preparing cell population which is comprised of NK cells, removing T cells from the cell population which is comprised of NK cells, and, after removal of T cells, cultivating the remaining cells in a medium supplemented with 2500 to 2831 IU/mL of IL-2. The method for amplifying NK cells of the present invention may comprise a step of removing hematopoietic progenitor cells from the cell population. The present invention provides a pharmaceutical composition for adoptive immunotherapy, comprising NK cells which are prepared by the amplifying method of the present invention.

Abstract: It is intended to provide a cancer stem cell and a method for preparing the same. The present invention provides a method for preparing a pluripotent cancer stem cell, comprising transferring Oct3/4, Sox2, Klf4, and c-Myc genes to an immortalized epithelial cell. The present invention also provides a pluripotent cancer stem cell as prepared by the above method.

Abstract: The present invention relates to novel therapies for treatment of new and existing type 1 and type 2 diabetes, PreDiabetes, Latent Autoimmune Diabetes of Adulthood, and diseases of insulin deficiency, beta cell deficiency, insulin resistance and impaired glucose metabolism. In particular, the present invention identifies common peptides within the human Reg1a, Reg1b, Reg3a and Reg4, as signaling peptides for beta cell generation acting through the human Reg Receptor on the surface of human pancreatic extra-islet tissue.

Abstract: A method for isolating human neuroepithelial precursor cells from human fetal tissue by culturing the human fetal cells in fibroblast growth factor and chick embryo extract and immunodepleting from the cultured human fetal cells any cells expressing A2B5, NG2 and eNCAM is provided. In addition, methods for transplanting these cells into an animal are provided. Animals models transplanted with these human neuroepithelial precursor cells and methods for monitoring survival, proliferation, differentiation and migration of the cells in the animal model via detection of human specific markers are also provided.

Abstract: A method is provided, including obtaining a population of antigen-presenting cells, enriching a population of stem/progenitor cells within a larger population of cells, activating the population of antigen-presenting cells and, following the activating, inducing at least one process selected from the group consisting of: differentiation, expansion, activation, secretion of a molecule, and expression of a marker, by exposing the enriched stem/progenitor cell population to the population of antigen-presenting cells. Other applications are also described.

Abstract: Antisense compounds, compositions and methods are provided for modulating the expression of C-reactive protein. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding C-reactive protein. Methods of using these compounds for modulation of C-reactive protein expression and for treatment of diseases associated with expression of C-reactive protein are provided.

Abstract: The present invention refers to agents for modulating the activity of proteins having a PWWP domain.

Abstract: Provided are a method of producing canine iPS cells, comprising (a) the step of bringing into contact with each other a canine somatic cell and a nuclear reprogramming factor, and (b) the step of culturing the cell in a medium containing at least one substance selected from the group consisting of a mitogen-activated protein kinase kinase inhibitor, an activin receptor-like kinase inhibitor, a glycogen synthase kinase inhibitor, a L-type calcium channel agonist and a DNA methylation inhibitor, and a leukemia inhibitory factor, and canine iPS cells that can be obtained by the method.

Abstract: Disclosed are fragments of oncofetal antigen, otherwise known as immature laminin receptor protein that specifically stimulate one T cell subclass. The fragments may be formulated into compositions for potentiating T cell-mediated responses in mammalian cancer patients. They also have therapeutic uses in vitro.

Abstract: Methods are provided for inducing non-pluripotent cells to become pluripotent. Methods also include identifying and isolating induced pluripotent (iPS) cells and uses thereof. Compositions and kits for carrying out the subject methods are also provided.

Abstract: [Problem] To provide a cell culture substrate, and a cell culturing method using the substrate and a method for inducing differentiation of pluripotent stem cells using the substrate, which allow culturing of pluripotent stem cells and allow differentiation of pluripotent stem cells into a specified cell species, particularly neural and neural progenitor cells, at a high purity. [Means for Solution] A cell culture substrate, characterized in that, onto the surface, one or more selected from the group consisting of N-cadherin, a fusion protein comprising an entire or partial region of N-cadherin, and a fusion protein comprising an entire or partial region of a protein homologous to N-cadherin are immobilized or coated.

Abstract: The purpose is to select low-molecular-weight compounds which are effective in inducing differentiation of mesenchymal stem cell into hepatocyte and to develop a safe differentiation-inducing method having excellent efficiency of differentiating mesenchymal stem cell into hepatocyte. Provided are at least one compound selected from the group consisting of compounds represented by formulae (1) and (2), a salt thereof, or a solvate of them; a differentiation inducer comprising at least one compound selected from the group consisting of compounds represented by formulae (1) and (2), a salt thereof, or a solvate of them; and a differentiation inducer comprising a compound represented by formula (8), a salt thereof, or a solvate of them.

Abstract: A unique type of regulatory T cell has been identified in muscle. These tissue-regenerative Treg cells play a role in regulating wound healing. These cells, as well as agents that control their differentiation and/or activity and agents produced by the cells, can be used to modulate wound healing and the differentiation of muscle cells.

Abstract: The present invention provides compounds and compositions for the amelioration of arthritis and joint injuries by inducing mesenchymal stem cells into chondrocytes.

Abstract: The present invention relates to a method of removing undifferentiated stem cells and dedifferentiated stem cells from a sample of cells. The invention further relates to preventing dedifferentiation of differentiated cells. Both methods comprise of administering to said cells an effective amount of compounds of formula (I): or a pharmaceutically acceptable salt thereof, wherein R1, R2, R3, n, p, Z and T are defined herein.

Abstract: The present invention relates to compositions and methods for generating populations of tissue precursor cells from pluripotent cells, and preferably induction of stem cells into definitive endoderm to generate anterior foregut endoderm from pluripotent cells. The anterior foregut endoderm cells can then be differentiated into an alveolar epithelial type II cell.

Abstract: Novel anti-cancer agents, including, but not limited to, antibodies and other polypeptides, that bind to human frizzled receptors are provided. Novel epitopes within the human frizzled receptors which are suitable as targets for anti-cancer agents are also identified. Methods of using the agents or antibodies, such as methods of using the agents or antibodies to inhibit Wnt signaling and/or inhibit tumor growth are further provided. Screening methods are also provided.

Abstract: This disclosure provides a newly developed strategy and particular options for differentiating pluripotent stem cells into cells of the hepatocyte lineage. Many of the protocols are based on a strategy in which the cells are first differentiated into early germ layer cells, then into hepatocyte precursors, and then into mature cells. The cells obtained have morphological features and phenotypic markers characteristic of human adult hepatocytes. They also show evidence of cytochrome p450 enzyme activity, validating their utility for commercial applications such as drug screening, or use in the manufacture of medicaments and medical devices for clinical therapy.

Abstract: Disclosed are engineered, living, three-dimensional connective tissue constructs comprising connective tissue cells. In some embodiments, the connective tissue cells are derived from multi-potent cells such as mesenchymal stem/stromal cells. In some embodiments, the cells are cohered to one another. In some embodiments, the multi-potent cells have been exposed to one or more differentiation signals to provide a living, three-dimensional connective tissue construct. In some embodiments, the constructs are substantially free of pre-formed scaffold at the time of use. Also disclosed are implants for engraftment, arrays of connective tissue constructs for in vitro experimentation, as well as methods of making the same.

Abstract: Provided are methods for activating an antigen-presenting cell and eliciting an immune response by inducing pattern recognition receptor activity, and CD40 activity. Also provided are methods for activating an antigen-presenting cell and eliciting an immune response by inducing CD40 activity without prostaglandin E2. Also provided are methods for activating an antigen-presenting cell and eliciting an immune response by inducing an inducible chimeric molecule comprising a region of a pattern recognition receptor or an adaptor thereof.

Abstract: Methods and compositions relating to the production of induced pluripotent stem cells (iPS cells) are disclosed. For example, induced pluripotent stem cells may be generated from peripheral blood cells, such as human blood progenitor cells, using episomal reprogramming and feeder-free or xeno-free conditions. In certain embodiments, the invention provides novel methods for improving overall reprogramming efficiency with low number of blood progenitor cells.

Abstract: The present invention is related to a nucleic acid, preferably binding to MCP-1, selected from the group consisting of Type 1A nucleic acids, type 1B nucleic acids, Type 2 nucleic acids, Type 3 nucleic acids, Type 4 nucleic acids and nucleic acids comprising SEQ ID NOs:87-115.

Abstract: We disclose a particle comprising a matrix coated thereon and having a positive charge, the particle being of a size to allow aggregation of primate or human stem cells attached thereto. The particle may comprise a substantially elongate, cylindrical or rod shaped particle having a longest dimension of between 50 ?m and 400 ?m, such as about 200 ?m. It may have a cross sectional dimension of between 20 ?m and 30 ?m. The particle may comprise a substantially compact or spherical shaped particle having a size of between about 20 ?m and about 120 ?m, for example about 65 ?m. We also disclose a method of propagating primate or human stem cells, the method comprising: providing first and second primate or human stem cells attached to first and second respective particles, allowing the first primate or human stem cell to contact the second primate or human stem cell to form an aggregate of cells and culturing the aggregate to propagate the primate or human stem cells for at least one passage.

Abstract: A method for the production of retinal cells, useful in transplantation therapy, comprises: (i) obtaining one or more mammalian adult Müller cells; and (ii) culturing the cells in the presence of an extracellular matrix protein and a growth factor to thereby induce dedifferentiation of the Müller cells into a progenitor phenotype.

Abstract: The present invention discloses novel dendritic cell maturation-inducing cytokine cocktails, and methods for inducting type-1 polarized dendritic cells in serum-free conditions which enhance the desirable properties of DC1s generated in serum-supplemented cultures. The invention further discloses methods and systems using IFN? and other ligands of the IFN? receptor, in combination with IFN? (or other type I interferons), poly I:C, and other IFN? (and IFN?) inducers to enhance the IL-12-producing properties of dendritic cells. More specifically, the present invention discloses type-1 polarized dendritic cells that have a unique combination of a fully-mature status and an elevated, instead of “exhausted”, ability to produce IL-12p70. allows for the generation of fully-mature DC1s in serum-free AIM-V medium.