Abstract: Various embodiments of the present invention include compositions, materials and methods for maintaining and propagating mammalian mesenchymal stem cells in an undifferentiated state in the absence of feeder cells and applications of the same.

Abstract: The present invention relates to methods of promoting the survival of cells by treating the cells with acid ceramidase. A kit for promoting ex vivo cell survival is also disclosed, as is a method of predicting in vitro fertilization outcome of a female subject.

Abstract: The invention relates to an artificial nucleic acid molecule comprising at least one 5?UTR element which is derived from a TOP gene, at least one open reading frame and optionally at least one 3?UTR element comprising a nucleic acid sequence which is preferably derived from the 3?UTR of a gene providing a stable mRNA, such as an albumin gene, or from a variant of the 3?UTR of a gene providing a stable mRNA. The invention further relates to the use of such an artificial nucleic acid molecule in gene therapy and/or genetic vaccination.

Abstract: The present invention relates to novel immunogens based on overlapping peptides (OLPs) and peptides derived therefrom useful for the prevention and treatment of AIDS and its related opportunistic diseases. The invention also relates to isolated nucleic acids, vectors and host cells expressing these immunogens as well as vaccines including the immunogens.

Abstract: Methods of cleaving double-stranded DNA that can be recognized and cleaved by a rationally-designed, I-CreI-derived meganuclease are provided. Also provided are recombinant nucleic acids, cells, and organisms containing such recombinant nucleic acids, as well as cells and organisms produced using such meganucleases. Also provided are methods of conducting a custom-designed, I-CreI-derived meganuclease business.

Abstract: The present invention relates to eukaryotic host cells having modified oligosaccharides which may be modified further by heterologous expression of a set of glycosyltransferases, sugar transporters and mannosidases to become host-strains for the production of mammalian, e.g., human therapeutic glycoproteins. The invention provides nucleic acid molecules and combinatorial libraries which can be used to successfully target and express mammalian enzymatic activities such as those involved in glycosylation to intracellular compartments in a eukaryotic host cell. The process provides an engineered host cell which can be used to express and target any desirable gene(s) involved in glycosylation. Host cells with modified oligosaccharides are created or selected. N-glycans made in the engineered host cells have a Man5GlcNAc2 core structure which may then be modified further by heterologous expression of one or more enzymes, e.g.

Abstract: Provided herein are methods to generate and screen peptides that exhibit drug like stabilities in vitro and in vivo. By selecting for enzyme resistance, Applicants are able to derive peptides that are not only stable to a broad spectrum of proteases, but also stable to other drug processing enzymes such as cytochrome P450s. This approach provides a general method to the rapid development of highly stable peptides for therapeutic development and diagnosis. The peptides are further modified for oral bioavailability.

Abstract: Disclosed is a method for producing pluripotent stem cell-enriched human dental pulp-derived cells. The method is characterized in that it includes (a) culturing a dental pulp suspension in a feeder cells-culture vessel containing feeder cells whose proliferative ability is suppressed, on a membrane having micropores that can block passage of the feeder cells and supported in the feeder cells-culture vessel in a manner to prevent the lower side face thereof from contacting with the feeder cells, thereby preventing direct contact with the feeder cells, and, (b) a step for recovering the cells proliferating on the membrane.

Abstract: The current invention provides methods to identify ?9?2T-cell receptors (?9?2TCR) that mediate anti-tumour responses. Surprisingly, it was now found that the CDR3 regions of the ?9-T-cell receptor chain and the ?2-T-Cell receptor chain (?2TCR chain) are of importance. Based on these findings, combinatorial-??TCR-chain-exchange (CTE) is proposed as an efficient method for identifying ?9?2TCRs that mediate anti-tumour responses. Using the method of the invention, specific sequences of the respective ?9TCR and ?2TCR chains were identified that mediate anti-tumour responses. Hence, the invention further provides for specific ?9?2TCRs, or fragments thereof, that may be used e.g. in diagnostics or treatment of cancer. The invention further provides for nucleic acid sequences, genetic constructs and retroviral vectors that can be used to express the ?9?2TCRs according to the invention.

Abstract: The present invention concerns the enhancement of the osteogenic potential of bone graft by ex vivo treatment with a Wnt polypeptide, such as a liposomal Wnt polypeptide.

Abstract: The present invention is directed to therapeutic multifunctional immature dental pulp stem cells (IDPSCs), and IDPSCs multi-lineage compositions. The invention is further directed to the use of IDPSCs and compositions to reduce the risk of and/or treat degenerative diseases or for other medicinal and aesthetic purposes.

Abstract: A method for suppressing an immune response is provided. The method involves administration of isolated lymphoid tissue-derived suppressive stromal cells (LSSC) to a subject in need of such treatment in an amount effective to suppress the immune response in the subject. The invention also involves a method to isolate LSSC by digesting lymphoid tissue fragments using a combination of an enzyme mix and agitation and then collecting the LSSC. Pharmaceutical preparations comprising LSSC are also provided.

Abstract: The embodiments provide for the modulation of both the differentiation and activity of human Th17 cells. More specifically, human Th17 cell differentiation can modulated by TGF-? and IL-21, and their agonists and antagonists. Function of Th17 cells can be modulated by, for example, BLT1 or podoplanin, and their agonists and antagonists. Additionally, the embodiments provide for the identification of Th17 cells. More specifically, human Th17 cells specifically upregulate BLT1 and podoplanin.

Abstract: The various embodiments herein provide a method for detecting the cancerous cells using the carbon nanotubes. The method comprises preparing a solution of the tissue cells. The prepared solution of the tissue cells is poured on a fabricated substrate to carry out an entrapment of the tissue cells on the substrate. The substrate is dried after the entrapment in an air ambient and observed under a scanning electron microscope. The cancer cell is detected based on the biomechanical properties such as softness, deformability and an elasticity of the cancer cells. The cancer cell is detected based on the deflection of the substrate due to the entrapment of the cancer cells.

Abstract: A three-dimensional microwell system that supports long term pluripotent cell culture and formation of homogeneous embryoid bodies (EBs) is described. Microwell-cultured pluripotent cells remain viable and undifferentiated for several weeks in culture and maintain undifferentiated replication when passaged to Matrigel®-coated, tissue culture-treated polystyrene dishes. Microwell-cultured pluripotent cells maintain pluripotency, differentiating to each of the three embryonic germ layers. Pluripotent cell aggregates released from microwells can be passaged for undifferentiated replication or differentiated to monodisperse EBs. The ability to constrain pluripotent cell growth in three dimensions advantageously provides for more efficient, reproducible culture of undifferentiated cells, high-throughput screening, and the ability to direct pluripotent cell differentiation by generating monodisperse EBs of a desired size and shape.

Abstract: The present invention relates generally to the fields of reproductive medicine. More specifically, the present invention relates to a novel human embryo co-culture system to improve human embryo growth in vitro and, consequently, increase pregnancy rates in infertile women undergoing in vitro fertilization (IVF) treatment. More particularly, the present invention relates to a method of growing an embryo to a blastocyst stage of development comprising the step of coculturing said embryo in the presence of a population of cumulus cells.

Abstract: A proliferation of cells can be reduced by contacting the cells with a compound having formula (I) where R and R? are each alkyl groups, R? is hydrogen or an alkyl group and X3, X4 and X5 are each independently selected from the group consisting of hydrogen, benzyl, t-butyldimethylsiloxy radical and triphenylmethyl. Accordingly, compounds of formula (I) can be used for treatment of tumors including melanoma. Also a secretion of a matrix metalloproteinase (MMP) enzyme by cells can be reduced by contacting the cells with the compound having formula (I). Accordingly, compounds of formula (I) can be used for treatment physiological conditions associated with an elevated MMP level, such as tumors.

Abstract: A composition includes an isolated cell; at least one particle within said cell; and at least one active agent associated with the particle, wherein the active agent is capable of being released from the cell. A method includes administration of such a cell to a subject.

Abstract: The present invention relates generally to the use of recombinant adeno-associated viruses (rAAV) for gene delivery and more specifically to the use of rAAV to deliver genes encoding human immunodeficiency virus entry inhibitors to target cells in mammals.

Abstract: The present invention relates to methods of isolating a substantially homogeneous population of pluripotent stem cells from adult neural crest tissue (e.g., periodontal ligament) as well as pharmaceutical compositions comprising such isolated pluripotent stem cells. Methods of inducing the isolated pluripotent stem cells into specific cell lineages, such as neurogenic and retinogenic lineages, are also described. The isolated pluripotent stem cells find use in various regenerative medicine applications and the treatment of degenerative diseases.

Abstract: The present invention provides compositions and methods for target radiotherapeutic treatment of cancer. Freshly isolated or culture expanded ELA stem cells are loaded with at least one of a diagnostic agent and a therapeutic agent, and the stem cells are then introduced into a subject. The loaded ELA stem cells migrate to location of cancer and form the basis both of diagnostic imaging and of directed Neutron Capture Therapy. Treatment of a subject may include ELA stem cell-based NCT radiotherapy as an adjunct to traditional therapies. An ELA stem cell-based diagnostic preparation can be used directly, or as a further addition to current imaging agents and methods.

Abstract: The invention described herein relates to the detection, diagnosis, and treatment of intestinal metaplasias that develop to esophageal, gastric, and pancreatic adenocarcinoma. The stem cells and differentiated cells of these intestinal metaplasias show high expression of CDH17 as well as other proteins. The invention also includes a clonal population of Barrett's esophagus stem cells as well as the stem cells of the surrounding normal epithelia and methods of using them for the detection, diagnosis, and treatment of Barrett's esophagus.

Abstract: An inactive CRISPR/Cas system-based fusion protein and its applications in gene editing are disclosed. More particularly, chimeric fusion proteins including an inCas fused to a DNA modifying enzyme and methods of using the chimeric fusion proteins in gene editing are disclosed. The methods can be used to induce double-strand breaks and single-strand nicks in target DNAs, to generate gene disruptions, deletions, point mutations, gene replacements, insertions, inversions and other modifications of a genomic DNA within cells and organisms.

Abstract: The present invention provides a method for the normalized culturing of corneal endothelial cells. More specifically, the present invention provides a culture-normalizing-agent of a corneal endothelial cell, comprising a fibrosis inhibitor. In detail, the present invention provides a culture-normalizing agent comprising a transforming growth factor (TGF) ? signal inhibitor. The present invention also provides a culture medium for culturing a corneal endothelial cell normally, which comprises the culture-normalizing agent according to the present invention and corneal endothelium culture components. The present invention also provides a method for culturing a corneal endothelial cell normally, comprising the step of culturing a corneal endothelial cell using the culture-normalizing agent according to the present invention or the culture medium according to the present invention.

Abstract: A cell culture bioreactor having a culture chamber for cell growth, a culture medium reservoir mounted externally to the culture chamber, a fluid circulation mechanism for moving culture medium from the reservoir through the culture chamber, and an aerating mechanism for introducing air into and removing air from the culture chamber is provided. The cell culture bioreactor comprises a manifold mechanism mounted at the top end of the culture chamber, a fluid circulation mechanism fluidly connected to the culture medium reservoir, for receiving culture medium from the culture medium reservoir and distributing culture medium into the culture chamber.

Abstract: Methods for generating high-yield, high-purity cardiomyocyte progenitors or cardiomyocytes from pluripotent cells are described. Wnt/?-catenin signaling is first activated in pluripotent cells, e.g., by inhibition of Gsk-3 to obtain a first population of cells. Wnt/?-catenin signaling is then inhibited in the first cell population to induce cardiogenesis under fully defined, growth factor free culture conditions.

Abstract: Isolated nucleic acids encoding polypeptides that exhibit butyrylcholinesterase (BChE) enzyme activity are disclosed, along with molecular criteria for preparing such nucleic acids, including codon optimization. Methods of preparing modified and/or truncated BChE molecules having selected properties, especially selective formation of monomers, are also described. Vectors and cells containing and/or expressing the nucleic acids are also disclosed.

Abstract: The present disclosure is directed to the development of compositions, such as extracellular matrices, and processes for using the same, that both maintain stem cells in vitro pluripotency and enable self-renewal. In this regard, it has been discovered that when pluripotent mouse and human embryonic stem cells are cultured on plates coated with recombinant laminin-10 (laminin-511) or their functional domains, in the absence of differentiation inhibitors or feeder cells, the embryonic stem cells proliferated and maintained their pluripotency.

Abstract: The present disclosure provides transformed human pluripotent stem cell (t-hPSC). t-hPSCs are not dependent on Oct4 for renewal and survival, however exhibit a sensitivity to reduced levels of the transcription factor Nanog. Also provided are methods of culturing cells for use in a cell-based screening assay comprising placing one or more transformed human pluripotent stem cells into a receptacle and culturing said stem cells in the receptacle to form a monolayer of stem cells without cell overlap. Methods of screening compounds using t-hPSCs are also described.

Abstract: A method of generating a population of cells useful for treating a nerve disease or disorder in a subject, the method comprising up-regulating a level of at least one exogenous miRNA in mesenchymal stem cells (MSCs) and/or down-regulating a level of at least one miRNA using a polynucleotide agent that hybridizes to the miRNA, thereby generating the population of cells useful for treating the nerve disease or disorder. Isolated populations of cells with an astrocytic phenotype generated thereby and uses thereof are also provided.

Abstract: Stromal stem cells are prospectively isolated from human bone marrow then expanded into clonal populations and cultured and used, the isolation being on the basis of expression of a cell surface marker, wherein the cell surface marker binds an antibody and wherein said antibody cross reacts with a cell surface marker found on mouse stromal stem cells or rat stromal stem cells, and optionally also on a cell of at least one other mammalian species selected from mouse, rat, horse, rabbit and pig cells. Useful stromal stem cell populations are positive for SDC2.

Abstract: The present invention relates to novel ?-AR homologous cyclopeptide-mutants comprising only two cysteine residues able to form an intramolecular linkage, to linear peptides that can form these cyclopeptide-mutants and to nucleic acid molecules encoding these cyclopeptide-mutants and linear peptides. Moreover, vectors and recombinant host cells comprising said nucleic acid molecule and a method for producing the disclosed cyclopeptide-mutants are provided. Further provided is a composition comprising the peptides, nucleic acid molecules, vectors or host cells of the invention. The present invention also relates to therapeutic and diagnostic means, methods and uses taking advantage of the peptides of the invention and to means, methods and uses for detecting anti-.beta.-adrenergic receptor antibodies like anti-?1-adrenergic receptor antibodies.

Abstract: The present invention provides small molecules useful to affect cancer cells, along with related methods. The present compounds, formulations, kits and methods are useful for a variety of research, diagnostic and therapeutic purposes. STAT3 inhibitors, particularly LLL12, are disclosed. The STAT3 inhibitors are useful to treat breast cancer in general and breast cancer initiating cells in particular.

Abstract: A tissue engineered construct made totally or in part from biocompatible materials and mammalian cells and/or cell products is provided. These constructs are useful in regenerating complex tissues such as bone, ligament and tendon, which may fabricated into medical devices suitable for use in the treatment of injuries and maladies such as rotator cuff injuries, periodontal disease and hernia.

Abstract: Human-derived fibroblast cells with copy number variation for alpha-synuclein, and methods of use thereof, are provided. For example, compositions and methods for high through-put screening of potential therapies for neurodegenerative disease such as Parkinson's disease are provided.

Abstract: A method of generating neural stem cells or motor neurons is disclosed, the method comprising up-regulating a level of at least one exogenous miRNA and/or down-regulating at least one miRNA using an agent which hybridizes to the miRNA in mesenchymal stem cells (MSCs) or down-regulating Related to testis-specific, vespid and pathogenesis protein 1 (RTVP-1).

Abstract: In certain aspects, the present invention provides compositions and methods for promoting bone growth and increasing bone density and strength. In certain embodiments, the present invention provides ALK3 polypeptides, including ALK3-Fc fusion proteins.

Abstract: Methods of generating functional human brown adipocytes, comprising exposing human stem cells, progenitor cells, or white adipocytes to culture with an differentiation cocktail that comprises one or more browning agents (e.g., one or more macromolecular crowders), and optionally one or more adipogenic agents, are described, as are populations of human brown adipocytes generated by the methods, and uses for the populations. Methods of generating functional human brown adipocytes in an individual, such as by administering a pharmaceutical composition comprising an differentiation cocktail, are also described.

Abstract: Methods are described for the delivery of one or more small interfering RNAs (siRNAs) to a eukaryotic cell using a bacterium. Methods are also described for using this bacterium to regulate gene expression in eukaryotic cells using RNA interference, and methods for treating an inflammatory disease or disorder. The bacterium includes one or more siRNAs or one or more DNA molecules encoding one or more siRNAs. Vectors are also described for use with the bacteria of the invention for causing RNA interference in eukaryotic cells.

Abstract: The present invention provides compositions and methods for transforming primary mammalian cells using an oncogenic form of ALK wherein the transformed cells display features of that of a corresponding tumor cell isolated from a cancer subject. The invention also provides a method for immortalizing normal CD4+ T lymphocytes with a lymphoma-characteristic form of ALK such as NPM-ALK.

Abstract: The present disclosure provides methods for maintaining and propagating undifferentiated pluripotent stem cells (SC) in suspension. The methods comprise culturing such SC in a non-adherent culture dish under conditions comprising a basic serum free medium and one or more of a basic medium, a serum replacement, an extra cellular matrix component and a factor supporting expansion of said SC. A specific and preferred culture condition comprise supplementing Neurobasal™ medium with KO serum replacement (KOSR). These conditions allowed for large scale and long term propagation of undifferentiated pluripotent SC. The culture system comprising suspended undifferentiated pluripotent SC were found to have many applications including in methods for directed as well as spontaneous differentiation of the SC into somatic cells. Also disclosed herein is a method of deriving SC, preferably human embryonic SC from human embryos via the formation of cell clusters.

Abstract: Provided herein is a three-dimensional scaffold composition comprising randomly oriented fibers, wherein the fibers comprise a polyethylene glycol-polylactic acid block copolymer (PEG-PLA) and a poly(lactic-co-glycolic acid) (PLGA). Also provided are methods for using the three-dimensional scaffolds described herein.

Abstract: The present invention demonstrates that P2X7 receptor induced apoptosis may be specific for cancerous cells. Treatment with the P2X7 ligand BzATP, increased cellular apoptosis with no associated inflammatory changes or abnormal skin or systemic effects. In mice treated with DMBA/TPA, BzATP decreased papilloma skin formation. BzATP also induced involution of developed papillomas and stimulated apoptosis in keratinocytes outgrowing at the base of developed papillomas. These data show that (a) P2X7 regulates apoptosis of epidermal cells; (b) in vivo, local administration of a drug that activates the P2X7 receptor can inhibit development and progression of epidermal premalignant lesions.

Abstract: Provided are engineered soluble hIL-17RA receptors with high affinity to hIL-17 that inhibit downstream IL17A induced signaling events in cells. Also provided are methods of inhibiting hIL-17A induced secretion of CXCL1 and/or IL-6 in cells, as well as methods of treating inflammation and/or inflammatory disorders in a subject.

Abstract: Methods of treating individuals with a glucose metabolism disorder and/or a body weight disorder, and compositions associated therewith, are provided.

Abstract: The methods of the present application describe that introduction of physiologically relevant miRNAs can enhance or modulate somatic cell reprogramming, generating induced pluripotent stem cells (iPS cells). These miRNAs did not further enhance reprogramming in the presence of cMyc. Furthermore, unlike previously described methods of generating iPS cells, such as through the introduction of genetic elements using viruses, the methods of the present invention reduce the risk of activating oncogenes in the iPS cells. The methods of the invention generate iPS cells that can be free of genetic modifications and thus have greater potential for use as therapeutic agents than those generated by existing methods.

Abstract: The present invention relates generally to the field of tissue engineering and in particular to the production of tissue films or cell matrices, which can be used as a living tissue substitute or an artificial tissue construct in tissue repair or replacement.

Abstract: Cells and cell lines that are genetically modified to express the hCox-2 enzyme, which results in the upregulation of prostaglandin F2 alpha (PGF2a) on the cells have been obtained. Encapsulated cell therapy devices containing such cells or cell lines that are capable of delivering PGF2a, as well as methods of using these devices to deliver PGF2a to the eye and to treat ophthalmic disorders in patients suffering therefrom are also described.

Abstract: The present invention provides an intercellular protein delivery system comprising an engineered peptide (EP), composed of secretion part (SP) and nuclear translocation part (NTP), a functional or therapeutic protein (FP), cells that express the fusion proteins and cells that accept the fusion proteins. The system can be used in vivo or in vitro to sustainably supply proteins of interest for cellular reprogramming, cellular differentiation and cell-based protein therapies.

Abstract: This invention relates to industrial production of proteins. More specifically, the invention relates to the res-DHFR surrogate marker, which corresponds to a fusion between DHFR and a protein conferring resistance to a toxic compound or conferring a metabolic advantage. The invention further relates to the use of res-DHFR for screening cells for high expression of a protein of interest. The invention is illustrated by the Puro-DHFR surrogate marker, which corresponds to a fusion between the puromycin N-acetyltransferase and dihydrofolate reductase (DHFR).