Abstract: The present invention provides for a recombinant nucleic acid molecule comprising a region of a calcium-calmodulin dependent kinase II? promoter operatively linked to a gene of interest. The region of a calcium-calmodulin dependent kinase II? promoter may comprise an 8.5 kilobase nucleic acid sequence which corresponds to the nucleic acid sequence of ATCC Accession No.: ______, designated pMM281. The present invention also provides a human cell line which has been stably transformed by a recombinant nucleic acid molecule comprising a gene of interest operatively linked to a nucleic acid encoding a calcium-calmodulin dependent kinase II? promoter region which has a nucleotide sequence corresponding to the sequence of ATCC Accession No. ______, designated pMM281. The present invention also provides for a transgenic nonhuman mammal whose germ or somatic cells contain a nucleic acid molecule which encodes a gene of interest under the control of a CaMKII? promoter (ATCC Accession No.

Abstract: The present invention relates to the production of functional neurons from adult human mesenchymal stem cells using a retinoid. A retinoid, when used in the absence of a growth factor, transdifferentiates mesenchymal stem cells into functional neurons that exhibit synaptic transmission. Moreover, polarization of the functional neurons can be achieved using selected growth factors. Functional neurons produced in accordance with the method of the invention find use in the treatment or amelioration of diseases or conditions associated with neurodegeneration or nerve damage.

Abstract: Disclosed are methods and compositions for early diagnosis, monitoring and treatment of retinal dystrophy, age-related macular degeneration, Bardet-Biedel syndrome, Bassen-kornzweig syndrome, best disease, chroidema, gyrate atrophy, congenital amourosis, refsun syndrome, stargardt disease and Usher syndrome. In particular, the invention relates to a protein, termed 2Rdcvf1,” that is differentially transcribed and expressed in subjects suffering from retinal dystrophies and the like, such as retinal dystrophy and age-related macular degeneration compared with non-sufferers, antibodies which recongnize this protein, and methods for diagnosing such conditions.

Abstract: A glial precursor cell population from mammalian central nervous system has been isolated. These A2B5+ E-NCAM? glial-restricted precursor (GRP) cells are capable of differentiating into oligodendrocytes, A2B5+ process-bearing astrocytes, and A2B5? fibroblast-like astrocytes, but not into neurons. GRP cells can be maintained by regeneration in culture. GRP cells differ from oligodendrocyte-type-2 astrocyte (O-2A) progenitor cells in growth factor requirements, morphology, and progeny. Methods of use of GRP cells are also disclosed.

Abstract: The invention provides methods of treating a subject having a disease, disorder or condition of the central nervous system. The methods include administering TGF-? polypeptides, related polypeptides, fragments and mimetics thereof useful in stimulating progenitor cell or stem cell proliferation, migration and differentiation. The methods of the invention are useful to treat and prophylactically ameliorate neurological tissue injury in vivo.

Abstract: The present invention features methods and compositions for treating a patient who has a neurological deficit. The method can be carried out, for example, by contacting (in vivo or in culture) a neural progenitor cell of the patient's central nervous system (CNS) with a polypeptide that binds the epidermal growth factor (EGF) receptor and directing progeny of the proliferating progenitor cells to migrate en masse to a region of the CNS in which they will reside and function in a manner sufficient to reduce the neurological deficit. The method may include a further step in which the progeny of the neural precursor cells are contacted with a compound that stimulates differentiation.

Abstract: Methods for enhancing survival and/or proliferation of neural stem cells and pharmaceutical compositions containing neural stem cells prepared by such methods, together with methods for assaying factors enhancing survival and/or proliferation of neural stem cells and methods for screening for such factors. Either Galectin-1 is overexpressed in neural stem cells or neural stem cells are cultured in a liquid medium containing Galectin-1. Pharmaceutical compositions containing Galectin-1-overexpressing neural stem cells and pharmaceutical composition containing Galectin-1, prepared by the aforementioned methods, improve higher cerebral functions damaged by cerebral ischemia.

Abstract: The present invention relates to an enriched or purified preparation of isolated hippocampal neural progenitor cells and progeny thereof. The present invention also relates to a method of separating neural progenitor cells from a mixed population of cell types from hippocampal tissue. This method includes selecting a promoter which functions selectively in the neural progenitor cells, introducing a nucleic acid molecule encoding a fluorescent protein under control of said promoter into all cell types of the mixed population of cell types from hippocampal tissue, allowing only the neural progenitor cells, but not other cell types, within the mixed population to express said fluorescent protein, identifying cells of the mixed population of cell types that are fluorescent, which are restricted to the neural progenitor cells, and separating the fluorescent cells from the mixed population of cell types, wherein the separated cells are restricted to the neural progenitor cells.

Abstract: A method for generating a culture that is purified or enriched in respect of cells of a selected lineage is described in which a selectable marker, which is differentially expressed in cells of the selected lineage compared with its expression in other cells, is introduced into a multipotential cell and the multipotential cell is cultured to induce differentiation of the multipotential cell into a cell of the selected lineage or into a mixture of cells including cells of the selected lineage, or is cultured to induce preferential survival of cells of the selected lineage. Those cells that express the selectable marker are then selected for. Progenitors of selected lineage are also described as is the use of the method in assay techniques.

Abstract: Compositions and methods are provided for the efficient and reproducible generation of clone animals of all developmental stages. Also provided are methods of use of the same in reproductive and therapeutic cloning protocols.

Abstract: A novel gene 65B13 expressed specifically and transiently in dopaminergic neuron precursor cells immediately after cell cycle exit was obtained by the present invention. The cellular expression of 65B13 can be used as an index to select cells that are suitable in terms of their safety, survival rate, and network formation ability, for transplant therapy of neurodegenerative diseases such as Parkinson's disease.

Abstract: Methods are described for mapping a pathway of differentiation of a population of embryonic cells that includes exposing the cells to an exogenous factor and measuring gene expression products that are characteristic of a particular cell type or lineage. Directing differentiation of human embryonic cells relies on dissociated embryoid bodies that are then exposed to one or more exogenous factors to enrich a culture for a particular cell type. The differentiated cells may be used for treating a medical condition in a human. Kits for determining differentiation pathways and screening exogenous factors for their utility in differentiation are provided.

Abstract: The present technology provides for a cell-synthesized biological thread, processes for making a cell-synthesized thread, and an apparatus for carrying out a process used to engineer the cell-synthesized thread. The thread is produced from living cells in culture and can be grown around the outer surface of a cylindrical bioreactor. The tissue comprising the thread has mechanical and biological properties achieved by altering the climactic conditions, stresses and strains on the tissue and chemical composition that prove beneficial in the medical industry. This process results in a biological thread that has high mechanical strength, decreased immunogenic effect and decreased thrombogenic effect when combined with other tissue. It also results in a product which can be used to create more complex constructs that otherwise could not have been generated. The threads can be used to make sutures, patches, and tubes, for example.

Abstract: This disclosure provides improved methods for obtaining populations of dopaminergic neurons from pluripotent stem cells. The process involves taking a population of neural precursor cells derived from a line of human embryonic stem cells, and culturing the cells in a medium that contains a neurotrophin, either cyclic adenosine monophosphate (cAMP) or a compound that elevates intracellular cAMP levels, and optionally an antioxidant such as ascorbic acid. Cell populations have been obtained that contain a high proportion of cells staining for tyrosine hydroxylase, which is a feature of dopaminergic neurons. The neural progenitors and terminally differentiated neurons of this invention can be generated in large quantities for use in drug screening and the treatment of clinically important neurological disorders, such as Parkinson's disease.

Abstract: The present invention is related to Preprocalcitonin antigen T epitopes, presented by the Major Histocompatibility Complex I (MHC I). These peptides can be used in cancer immunotherapy.

Abstract: The present invention relates to human, rat and mouse stem cell-derived neuron survival factor polypeptides (SDNSF), a process for producing them, cDNA encoding SDNSF, a vector comprising the cDNA, host cells transformed by the vector, an antibody against SDNSF, pharmaceutical compositions containing SDNSF or the antibody, a method of assaying SDNSF, a reagent for assaying SDNSF, and a screening method using SDNSF. The polypeptides are effective in the survival of nerve cells and, therefore, efficacious in treating injury to the central nerve system caused by brain infarction, brain hemorrhage, spinal cord injury, etc.

Abstract: A method of promoting neuronal regeneration includes administering an agent to at least one neural cell in contact with at least one neural cell growth inhibiting component in an amount effective to promote neuronal regeneration. The agent is selected from the group consisting of a Class I Rho family GTPase, a C1 activator, a Class II Rho family GTPase, and a C2 inhibitor.

Abstract: The present invention provides a method of determining clostridial toxin activity by (a) contacting with a sample a cell containing a clostridial toxin substrate that includes a donor fluorophore; an acceptor having an absorbance spectrum overlapping the emission spectrum of the donor fluorophore; and a clostridial toxin recognition sequence containing a cleavage site that intervenes between the donor fluorophore and the acceptor, where resonance energy transfer is exhibited between the donor fluorophore and the acceptor under the appropriate conditions; (b) exciting the donor fluorophore; and (c) determining resonance energy transfer of the contacted cell relative to a control cell, where a difference in resonance energy transfer of the contacted cell as compared to the control cell is indicative of clostridial toxin activity.

Abstract: The development and function of living tissues depends largely on interactions between cells that can vary in both time and space; however, temporal control of cell-cell interaction is experimentally challenging. By employing a micromachined silicon substrate with moving parts, herein is disclosed the dynamic regulation of cell-cell interactions via direct manipulation of adherent cells with micron-scale precision. The inventive devices and methods allow mechanical control of both tissue composition and spatial organization. The inventive device and methods enable the investigation of dynamic cell-cell interaction in a multitude of applications, such as intercellular communication, spanning embryogenesis, homeostasis, and pathogenic processes.

Abstract: The present invention relates to a method for delivering a nucleic acid sequence encoding neuropeptide Y, or a derivative or functional fragment thereof, to a mammalian nervous system target cell. The expression of exogenous NPY, or a derivative or a functional fragment thereof in the target cell(s) provides therapeutic benefit for subjects afflicted with a neurological disorder.

Abstract: Hair follicle stem cells are isolated by virtue of understanding their location within the hair follicle during telogen phase.

Abstract: This invention relates to the novel identification of arginase as an enzymatic activity which can reverse inhibition of neuronal regeneration in the central and peripheral nervous system. Assays to monitor the effects of various agents on arginase expression and thus on neuronal regeneration and repair and to identify agents which will block or promote the inhibitory effects on neuronal outgrowth are provided. This invention also relates to compositions and methods using agents that can reverse the inhibitory effects of myelin on neural regeneration by affecting arginase activity or putrescine and derivative polyamine levels in a neuron.

Abstract: A method for producing a neuroblast and a cellular composition comprising an enriched population of neuroblast cells is provided. Also disclosed are methods for identifying compositions which affect neuroblasts and for treating a subject with a neuronal disorder, and a culture system for the production and maintenance of neuroblasts.

Abstract: The subject invention pertains to compositions and methods for culturing nerve tissue in vitro and nerve grafts produced using such methods. The compositions and methods of the subject invention can be employed to restore the continuity of nerve interrupted by disease, traumatic events or surgical procedures. The invention also concerns methods for promoting repair of damaged nerve tissue using the present compositions and nerve tissue treated according to such methods.

Abstract: This inventive discloses a method for transdifferentiating mesenchymal stem cells into neuronal cells, which comprises increasing the level of a basic helix-loop-helix (bHLH) transcription factor in the mesenchymal stem cells, said cells being useful in cell therapy or gene therapy for treating brain neurological diseases such as Parkinson's disease, Alzheimer disease, Hungtington's disease, amyotrophic lateral sclerosis, cerebral paralysis and brain ischemia; and spine disfunction caused by a traumatic injury.

Abstract: The invention relates to methods and reagents for promoting the differentiation of oligodendrocytes from stem cells, by co-activating the Olig genes and the Nkx2.2 genes, and the use of the differentiated oligodendrocytes thus obtained in treating diseases, such as Multiple Sclerosis (MS). The invention also relates to the use of OLPs and oligodendrocytes thus obtained for drug screening.

Abstract: As described below, the present invention features methods for reprogramming somatic cells and related therapeutic compositions and methods.

Abstract: This invention relates to methods of producing oligodendrocytes from multipotent neural stem cells by using at least one oligodendrocyte promoting factor, particularly granulocyte-macrophage colony stimulating factor, granulocyte colony stimulating factor, interleukin 3 or interleukin 5. The neural stem cells may optionally be expanded prior to being subjected to the oligodendrocyte promoting factor.

Abstract: A method of treating mucus hypersecretion, the causative factor in chronic obstructive pulmonary disease (COPD), asthma and other clinical conditions involving COPD, comprises administering a compound that inhibits exocytosis in mucus secreting cells or neurones that control or direct mucus secretion. Also described is a compound, for use in the treatment of hypersecretion of mucus, which inhibits mucus secretion by inhibiting mucus secretion by mucus secreting cells, and/or inhibiting neurotransmitter release from neuronal cells controlling or directing mucus secretion.

Abstract: Novel methods are provided for modulating CNS cell neogenesis in the CNS cells in vitro or in vivo, involving the use of agents that decrease the activity of the melanocortin 4 receptor (MC4R). When the methods of the invention are applied to a subject such as a human, it may be used for reducing a symptom of a CNS disorder.

Abstract: Methods and materials to modulate the immune response to treat or prevent a disease or to prevent transplant rejection, including methods of making T helper-antigen presenting cells and/or T regulatory-antigen specific cells and methods of using these cells. The invention also relates to methods of making exosome-absorbed dendritic cells and the uses of these cells to modulate the immune response to treat or prevent a disease or to prevent transplant rejection.

Abstract: Compositions and methods are provided for preventing or treating neoplastic disease in a mammalian subject. A composition is provided which comprises an enriched immune cell population reactive to a human endogenous retrovirus type E antigen on a tumor cell. A method of treating a neoplastic disease in a mammalian subject is provided which comprises administering to a mammalian subject a composition comprising an enriched immune cell population reactive to a human endogenous retrovirus type E antigen, in an amount effective to reduce or eliminate the neoplastic disease or to prevent its occurrence or recurrence.

Abstract: It is an object of the present invention to apply a novel method of preparing neural cells from ES cells. The method of the present invention is characterized by the electric pulse treatment of differentiating ES cells. Nerve cells obtained by the method of the present invention have the flexibility to differentiate into a variety of types of neurons in vivo preferably without the need for application of growth factors.

Abstract: This invention relates to methods of producing oligodendrocytes from multipotent neural stem cells by using at least one oligodendrocyte promoting factor, particularly granulocyte-macrophage colony stimulating factor, granulocyte colony stimulating factor, interleukin 3 or interleukin 5. The neural stem cells may optionally be expanded prior to being subjected to the oligodendrocyte promoting factor.

Abstract: Enriched neural stem and progenitor cell populations, and methods for identifying, isolating and enriching for neural stem cells using reagent that bind to cell surface markers, are provided.

Abstract: A method of treating neurodegenerative conditions is provided. Neural stem cells may be implanted at and/or remote from a region of neuron degeneration. The methods can include isolating neural stem cells from regions where specific types of neurons corresponding to the neurons to be replaced are generated. The methods can include isolating neural stem cells secreting growth factors affecting the growth and/or regeneration of specific types of neuron. In this invention, we disclose a method of treating such disorders, including several neurodegenerative disorders arising from the lack of cells that produce particular neurotransmitters in neural circuitry by transplanting exogenously cultured and expanded neural progenitors which, upon transplantation into a neural tissue, differentiate into neurons capable of integrating and producing neurotransmitters in sufficient quantities and in a sufficient manner to overcome the symptoms associated with the neurodegeneration.

Abstract: This invention relates to methods for promoting myelination, neuronal survival, and oligodendrocyte differentiation and treating demyelination and dysmyelination disease by the administration of a TrkA antagonist. The invention also relates to methods of inhibiting or decreasing Sp35 expression by the use of a TrkA antagonist. Additionally, the invention relates generally to methods for blocking Sp35 and TrkA interaction and inhibiting or decreasing TrkA phosphorylation by the administration of a Sp35 antagonist.

Abstract: The present inventors concerns vectors carrying a truncated chimeric CMV-chicken ?-actin (smCBA) promoter in which the hybrid chicken ?-actin/rabbit ?-globin intron is greatly shortened, and their use to deliver to an operatively linked polynucleotide to host cells in vitro or in vivo, resulting in expression of the polynucleotide in the host cells. In one embodiment, the vector carrying the smCBA promoter is administered to the eye. In another embodiment, the vector carrying the smCBA promoter is a self-complementary adeno-associated virus (AAV). The AAV vector may be of any serotype (e.g., type 1, type 2, type 3, type 4, type 5, type 6, type 7, type 8, type 9, type 10). In another embodiment, a self-complementary vector carrying the smCBA promoter is administered to the eye. Another aspect of the invention concerns host cells carrying a vector of the invention.

Abstract: The present disclosure is directed to improved methods for efficiently producing neuroprogenitor cells and differentiated neural cells such as dopaminergic neurons and serotonergic neurons from pluripotent stem cells, for example human embryonic stem cells. Using the disclosed methods, cell populations containing a high proportion of cells positive for tyrosine hydroxylase, a specific marker for dopaminergic neurons, have been isolated. The neuroprogenitor cells and terminally differentiated cells of the present disclosure can be generated in large quantities, and therefore may serve as an excellent source for cell replacement therapy in neurological disorders such as Parkinson's disease.

Abstract: Coupling of excitation to neurogenesis in proliferating post-natal NPCs is demonstrated in vitro and in vivo. Neurogenesis is potently enhanced by excitatory stimuli, and involves Cav1.2/1.3 channels and NMDA receptors. These Ca2+ influx pathways are located on the proliferating NPCs, allowing them to directly sense and process excitatory stimuli. Excitation increases the fraction of NPC progeny that are neurons, and increases total neuron number. Signaling in this pathway leads to rapid induction of a proneural gene expression pattern involving the bHLH genes HES1, Id2, and NeuroD, and the resulting cells become fully functional neurons defined by neuronal morphology, expression of neuronal structural proteins, expression of neuronal TTX-sensitive voltage gated Na+ channels, and synaptic incorporation into active neural circuits.

Abstract: The present invention relates to cells obtainable from cell lines having the ECACC Accession Nos 04091601, 04110301 and 04092302.

Abstract: The object of the present invention is to provide methods for inhibiting proliferation of neural stem cells, an agent for inhibiting proliferation of neural stem cells, and methods for using the same. According to the method of the present invention, a galectin-1 inhibitor such as anti-galectin-1 antibody and/or an integrin ?1 inhibitor such as anti-integrin ?1 antibody is administered to a human or a vertebrate other than human for inhibiting proliferation of neural stem cells. This method can be used for treatment of nerve injury and nerve tumors.

Abstract: The invention provides neuron-derived cells obtained by transfecting a receptor-expressing nucleic acid having an aryl hydrocarbon receptor gene, wherein outgrowth of neurites is not observed without adding a substance for the aryl hydrocarbon receptor, and outgrowth of neurites is observed by adding the substance for the aryl hydrocarbon receptor. The invention also provides a method for determining the presence of neurotoxicity of a test substance, a method for acquiring a marker for determining the presence of neurotoxicity of the test substance, a method for acquiring a marker for neurological dysfunction, and a method for determining the effect of the test substance on neurological dysfunction using such cells.

Abstract: Disclosed are embryonic stem cells and motor neurons derived from mice carrying transgenic alleles of the normal or mutant human SOD1 gene. Also disclosed are in vitro systems employing such SOD1 transgenic motor neurons for the study of neural degenerative disease.

Abstract: The present invention is based upon a surprising finding that stem cells, more particularly neural stem cells, can migrate throughout a brain tumor and track metastatic brain tumor cells. The invention provides a method for treating brain tumors by administering genetically engineered neural stem cells in an individual affected by brain tumors. The invention also provides a method of preparing genetically engineered neural stem cells and a composition comprising genetically engineered neural stem cells in a pharmaceutically acceptable carrier.

Abstract: Isolated human cells and populations thereof are provided comprising at least one oligodendrocyte phenotype and at least one mesenchymal stem cell phenotype, wherein the mesenchymal stem cell phenotype is not an oligodendrocyte phenotype. Methods of generating and using same are also provided.

Abstract: Cultures of cells immunoreactive for glial fibrillary acidic protein (GFAP), as well as for the intermediate filament marker nestin were grown in a medium including epidermal growth factor (EGF) and serum. The cultured cells had the morphology of astroglial cells. The cells can be proliferated in adherent or suspension cultures. Depending on the culture conditions, the cells can be induced to differentiate to neurons or glial cells. The cultures can be expanded over a large number of passages during several months, and survive, express an astroglial phenotype and integrate well after transplantation into both neonatal and adult rat forebrain.

Abstract: Provided are tissue scaffolds colonized by vertebrate cells expressing a transgenic bioactive molecule, where the vertebrate cells are unable to undergo mitosis. Also provided are methods of growing tissue in a mammal and methods of delivering a transgenic bioactive molecule to a tissue of a mammal, using the tissue scaffolds. Additionally, methods of making the tissue scaffolds are provided.

Abstract: A method of generating neural and glial cells is provided. The method comprising growing human stem cells under conditions which induce differentiation of said human stem cells into the neural and glial cells, said conditions comprising the presence of retinoic acid and an agent capable of down-regulating Bone Morphogenic Protein activity.

Abstract: The invention provides methods and compositions for identifying agents which modulate cell death, indicated e.g. by the expression of caspase-2 and/or caspase-7, in GDNF family growth factor deprived neuronal or nonneuronal cells. The methods for identifying such agents find particular application in drug development.