Abstract: The disclosure provides polynucleotides containing regions of the Myosin 15 (Myo15) promoter, as well as vectors containing the same, that can be used to promote expression of a transgene specifically in hair cells. The polynucleotides described herein may be operably linked to a transgene, such as a transgene encoding a therapeutic protein, so as to promote hair cell-specific expression of the transgene. The polynucleotides described herein may be operably linked to a therapeutic transgene and used for the treatment of subjects having or at risk of developing hearing loss or vestibular dysfunction.

Abstract: Disclosed are methods of preparing thymic emigrant cells in vitro, isolated or purified thymic emigrant cells prepared by the methods, and pharmaceutical compositions comprising the same. Further disclosed are methods of treating or preventing a condition in a mammal comprising administering the thymic emigrant cells or pharmaceutical compositions comprising the same to the mammal.

Abstract: The present invention relates to methods of generating and expanding hitman embryonic stem cell derived mesenchymal-like stem/stromal cells. These hES-MSCs are characterized at least in part by the low level of expression of IL-6. These cells are useful for the prevention and treatment of T cell related autoimmune disease, especially multiple sclerosis, as well as for delivering agents across the blood-brain barrier and the blood-spinal cord barrier. Also provided is a method of selecting clinical grade hES-MSC and a method of modifying MSC to produced a MSC with specific biomarker profile. The modified MSC are useful for treatment of various diseases.

Abstract: The present invention relates generally to the identification and isolation of human otic progenitor cells. More specifically, the present invention relates to a method of using cell markers to identify and isolate human otic progenitor cells from a mixed population of cells, methods of enrichment and production of human otic progenitor cells, and associated kits for use in identification and/or isolation of human otic progenitor cells, wherein the cell markers are selected from SSEA1 (CD15), disialoganglioside GD3, TRA-2-49 (liver/bone/kidney alkaline phosphatase), SSEA4, ganglioside GD2 and CD141.

Abstract: The present disclosure relates to the use of laminin-521 in obtaining retinal pigment epithelium (RPE) cells. Pluripotent human embryonic stem cells are cultured on plates coated with recombinant laminin-521 (laminin-11), in totally defined and xeno-free conditions. A first cell culture medium contains a growth factor, and a second cell culture medium does not contain growth factor. The stem cells are first exposed to the first cell culture medium, then exposed to the second cell culture medium for a longer time period. After a number of weeks, clinical grade RPE cells are obtained from the stem cells.

Abstract: Disclosed herein are methods and associated compositions and kits for identifying nucleoside modifications. Particularly exemplified herein are methods that involve inducing base misincorporation at locations in an RNA that harbor a nucleoside modification. The resulting cDNA can then be subjected to next generation sequencing to identify mutations with respect to a reference sequence. Moreover, the type of nucleoside modification can be determined based on the substitution pattern of a given nucleoside modification.

Abstract: Methods and compositions for rapid development of reporter lines utilizing safe harbor sites in iPSCS, as well as other progenitor cells, pluripotent and multipotent stem cells and differentiated cells, and multiple Lox sites are provided.

Abstract: A method of treating neurodegenerative diseases using hUCB plasma is presented herein. hUCB plasma attenuated the hyperactive response (Group III) and potentiated the normal response in Group I ALS patients, but did not alter that of the non-responders to PHA (Group II). The elevated activity of caspase 3/7 observed in the MNCs from ALS patients was significantly reduced by hUCB plasma treatment. The ability of hUCB plasma to modulate the mitogen cell response and reduce caspase activity suggest that the use of hUCB plasma alone, or with stem cells, may prove useful as a therapeutic in ALS patients. hUCB plasma was shown to increase therapeutic efficacy of MNCs as well as decrease apoptosis of MNCs. The cytokine profile of hUCB plasma supports its usefulness as a sole therapeutic as well as an additive to MNCs.

Abstract: Methods for producing therapeutic T cells from umbilical cord blood are provided. Methods for treating immune-related diseases or conditions (e.g. autoimmune diseases, transplant rejection, cancer) using umbilical cord blood derived therapeutic T cells are also provided. Compositions comprising umbilical cord blood derived therapeutic T cells are also provided.

Abstract: The invention provides a method for inducing adenohypophysis or precursor tissue thereof in vitro from human pluripotent stem cells. The method includes culturing an aggregate of human pluripotent stem cells in suspension in a medium containing a bone morphogenetic protein signal transduction pathway activating substance and a substance acting on the Shh signal pathway to obtain a human cell aggregate containing a hypothalamus neuroepithelial tissue and a surface ectoderm, and further culturing the obtained human cell aggregate containing the hypothalamus neuroepithelial tissue and the surface ectoderm in suspension in a medium containing a bone morphogenetic protein signal transduction pathway activating substance and a substance acting on the Shh signal pathway to induce formation of hypophysial placode and/or Rathke's pouch in the surface ectoderm, thus obtaining a human cell aggregate containing 1) hypothalamus neuroepithelial tissue, and 2) hypophysial placode and/or Rathke's pouch.

Abstract: Methods are provided for producing differentiated cells from stem cells, including producing hepatocytes. Compositions thereof are also provided, as are methods of treating a liver disorder.

Abstract: Described herein are chemically defined, adherent culture protocols for generating functional motor neurons characteristic of diverse hindbrain and spinal cord regions, with high efficiency.

Abstract: A method for producing a cell culture containing desired cells is provided. The desired cells are induced to be differentiated from pluripotent stem cells. The method includes seeding a cell population by dispersing embryoid bodies obtained by inducing differentiation from the pluripotent stem cells to the desired cells. The embryoid bodies are dispersed at a density reaching confluence or higher.

Abstract: A method of making a porous three-dimensional graphene mesh includes combining a graphene-containing material and a polymer having a plurality of hydroxyl groups in an alcohol solvent to form a mixture, adding a salt to the mixture, heating the mixture to form a gel, and washing the gel with water to remove the salt from the gel, leaving behind stable pores to form a scaffold. A three-dimensional porous graphene mesh includes a graphene-containing material and a polymer. The polymer is crosslinked with the graphene-containing material such that the Young's Modulus of the mesh is at least about 5 GPa.

Abstract: The present invention is directed to a biocompatible adhesive system comprising a) a hydrogel comprising a first polymer network and a second polymer network, wherein the first polymer network comprises covalent crosslinks and the second polymer network comprises ionic crosslinks; b) a high density primary amine polymer; and c) a coupling agent. The present invention also provides methods preparing and using the biocompatible adhesive system.

Abstract: The present invention chiefly aims to provide a process for directly inducing insulin-producing cells from somatic cells without performing artificial gene transfer. The present invention can include a process for producing an insulin-producing cell by inducing differentiation directly from a somatic cell, the process comprising a step of culturing the somatic cell in the presence of a cAMP inducer, and six members selected from the group consisting of a GSK3 inhibitor, a TGF-? inhibitor, a BMP inhibitor, a p53 inhibitor, a PI3K inhibitor, a Notch inhibitor and a RAR agonist, or all members thereof. The insulin-producing cells obtained by the present invention are useful in regenerative medicine and the like.

Abstract: Provided herein are cells and methods for reprogramming iPS cells from a supercentenarian and their differentiated derivatives having differences from non-supercentenarian iPS derived cells that contribute to disease resistance and longevity. Additionally, provided herein are methods for treatment and prevention of age related diseases by administration of therapeutic sciPS derived cells or cell derived reagents. Also provided herein, are methods for identifying reagents for treatment of age related diseases using sciPS cell-based assays.

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 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: 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: 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: 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 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 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.