84 results about "Neuroglial cells" patented technology

A novel neurotrophic factor referred to as glial cell line-derived neurotrophic factor (GDNF) has been identified and isolated from serum free growth conditioned medium of B49 glioblastoma cells. Rat and human genes encoding GDNF have been cloned and sequenced. A gene encoding GDNF has been subcloned into a vector, and the vector has been used to transform a host cell in order to produce biologically active GDNF in a recombinant DNA process.

A statistical and functional correlation strategy to identify changes in cellular pathways specifically linked to impaired cognitive function with aging. Analyses using the strategy identified multiple groups of genes expressed in the hippocampi of mammals, where the genes were expressed at different levels for several ages. The aging changes in expression began before mid-life. Many of the genes were involved in specific neuronal and glial pathways with previously unrecognized relationships to aging and / or cognitive decline. The processes identified by the strategy suggest a new hypothesis of brain aging in which initially decreased neuronal activity and / or oxidative metabolism trigger separate but parallel genomic cascades in neurons and glia. In neurons, the cascade results in elevations in calcium signaling and reductions of immediate early gene signaling, biosynthesis, synaptogenesis and neurite remodeling. In contrast, glia undergo increased lipid metabolism and mediate a cycle of demyelination and remyelination that induces antigen presentation, inflammation, oxidative stress and extracellular restructuring. These identified genes and the proteins they encode can be used as novel biomarkers of brain aging and as targets for developing treatment methods against age-related cognitive decline, Alzheimer's Disease and Parkinson's Disease.

The invention provides a neural stem cell (NSC) strain. The NSC strain can be isolated from animal brain tissues from different species. Embryonic stem cells (ES), induced pluripotent stem cells and other stem cells can be differentiated into the NSC. The NSC strain is characterized by quick proliferating and stable passaging; prolonged expressing biomarker proteins of Oct4 and Sox1; high efficient being differentiated into a plurality of neurons and glial cells. The invention further provides an establishing method and an application for the NSC.

The present invention provides methods for generating oligodendrocyte progenitor cells from pluripotent cells, as well as methods for sustaining these oligodendrocyte progenitor cells in relatively pure cultures for long periods of time. The present invention also provides methods for further differentiating these oligodendrocyte progenitor cells into various glial cells.

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.

Disclosed is an in vitro method of transdifferentiating an epidermal basal cell into a cell having one or more morphological, physiological and / or immunological features of a glial cell. Also disclosed are such transdifferentiated cells and cell cultures derived from them. A kit for converting, in vitro, epidermal basal cells into cells having one or more morphological, physiological and / or immunological features of a glial cell is also disclosed.

Provided is a composition for treating nerve damage-related diseases. The composition includes a human umbilical cord blood-derived mesenchymal stem cell as an active ingredient. The mesenchymal stem cell isolated and incubated from the human umbilical cord blood migrates to an injured area to be differentiated into a nerve cell or a neuroglial cell at the time of in vivo transplantation. Thus, the mesenchymal stem cell and a composition including the same can be effectively used in cell replacement therapy and gene therapy for treating diseases caused by nerve damage including a stroke, Parkinson's disease, Alzheimer's disease, Pick's disease, Huntington's disease, amyotrophic lateral sclerosis, traumatic central nervous system disease and a spinal cord injury.

The invention relates to a preparation method of a neural stem cell and particularly discloses a method for inducing a human mesenchymal stem cell to obtain the neutral stem cell. The method comprises the step of sequentially cultivating the mesenchymal stem cell in first, second and third culture media to obtain the neural stem cell. The finally obtained neural stem cell expresses a mark of an early neural stem cell and can be differentiated to functional neuron and neurogliocyte.

Methods for producing a population of human-derived glial restricted progenitor cells (GRPs) with decreased potentially unintended or undesired cellular phenotypes and / or decreased standard deviation in the cells of the population are provided. Also provided are antibody panels and gene expression profiles to characterize GRPs and a method for its use in characterizing GRP cells. In addition methods for use of these GRP cells to generate astrocytes and / or oligodendrocytes, to re-myelinate neurons and to treat glial cell related and other neurodegenerative diseases or disorders or injuries or damage to the nervous system are provided. A method to manufacture neural cells depleted of A2B5 positive cells is also provided.

The invention discloses an application of gastrodin to preparing medicaments for preventing and treating Alzheimer's disease. Alzheimer's disease (AD) is a neurodegenerative disease, and pathological characteristics comprise neuro fibrillary tangles formed in cells, hyperplasia of reactive microglia and glial cell, and the like, wherein the extracellular deposition of amyloid A beta is the main pathogenetic reason of AD. An AD small mouse taking a gastrodin-containing fodder is substantially improved in spatial-memory learning ability, substantially reduced in A beta level in brain and serum, and substantially reduced in amyloid plaques and microglia in brain tissue, and thus it is indicated that gastrodin is capable of preventing A beta deposition and decreasing active components causing AD mouse brain gastrodin.

Compositions and methods for treating patients with preexisting neuronal damage are disclosed. The compositions and methods use an adeno-associated virus (AAV)-based gene delivery system to deliver glial cell-derived neurotrophic factor (GDNF) to patients with neurodegenerative disorders, such as Parkinson's disease. .

The present invention relates to the reprogramming of differentiated somatic cells, such as those differentiated cells that arise from embryonic mesoderm, into glial cells. Glial cells produced from this reprogramming are functionally equivalent to glial cells that arise from ectodermal origins.

A micro fluidic device comprises one microstructure layer (5) and one cover layer (1), wherein the cover layer (1) is connected to the microstructure layer (5). The microstructure layer (5) comprises one bottom layer and a plurality of microstructures on it to position samples. The cover layer (1) comprises one top layer, one positioning well (6) and at least one inlet pool (4). The positioning well (6) is right above the microstructures and connected with each other. The inlet pools (4) and the positioning well (6) are connected by microchannels (3) which are formed between the microstructure layer (5) and the cover layer (1). The micro fluidic device can be applied in vitro fertilization, in determining how glial cells affect neurons, in constructing neural network and in detecting cell growth conditions.

The invention relates to the cytobiology field, and discloses a neuronal cell and neuroglial cell ordered co-culture device and a preparation method and an application thereof. The device includes a substrate and a polydimethylsiloxane stamper, wherein the polydimethylsiloxane stamper can be removably compounded on the substrate; the polydimethylsiloxane stamper includes at least one micropore unit, the micropore unit includes at least one first through hole perpendicular to the substrate and at least one second through hole perpendicular to the substrate, the first through hole and the second through hole are arranged successively, and the first through hole and the second through hole respectively with the surface of the substrate form grooves having one end with an opening; the distance between the first through hole and the second through hole is 500 [mu]m-2000 [mu]m. Neuronal cells and neuroglial cells are inoculated through the first through hole and the second through hole which are perpendicular to the substrate, uniformity of the two kinds of cells is easy to control during inoculation in regions, cell quantity which can be used is increased, a population effect is obvious, and observation and study are facilitated.

The present invention describes a dissociated cell culture system comprising cells of the hippocampus, one of the brain areas affected by Alzheimer's Disease (AD) or amyloid beta-related diseases. This culture system comprises hippocampal neuronal and glial cells from animal models of AD, particularly, but not limited to, double transgenic mice expressing both the human APP mutation (K670N:M671L) (mAPP), and the human PS1 mutation (M146L) (mPS1), and serves as a powerful tool for the screening and testing of compounds and substances, e.g., drugs, for their ability to affect, treat, or prevent AD or β-amyloid-related diseases. The effects of a test substance on the cells in this culture system can be quantitatively assessed to determine if the test substance affects the cells biochemically and / or electrophysiologically, and / or optically, and / or immunocytochemically. The present in vitro culture system is advantageous for AD drug screening, because it is rapid and efficient. By contrast, even in the fastest animal model of AD, pathology does not start before the end of the second month. If such in vivo animal models are used, it is necessary to wait at least the two month time duration or longer to test for drug efficacy for AD treatment or prevention. At the same time the present invention provides a tool for production of amyloid-beta that can be used for electrophysiological, behavioral, and toxicological studies.

The present invention discloses conjugated of glycine with glutamic acid receptor, and can activate the receptor, the number of glycines existed in the synaptic neural gap can be regulated by glycine transferase found in the neuroglial cell, so that the inhibitor of glycine transferase can increase the glycine in the synoptic neural gap, and can be used as medicine for activating glutamic acid receptor and for curing schizophrenia. Said invention also discloses a new compound with physiological activity, said new compound has inhibiting activity for glycine transferase of glycine cell and is produced by microbial fermentation.

The invention makes 24-site mutation on natural scorpion chlorine ion channel neurotoxin gene BmK CT according to the principle of Escherichia coli partial to codon, designs DNA sequence suitable to be expressed in Escherichia coli BL21 (DE3), adopts PCR technique to complete artificial synthesis of recombinant scorpion chlorine ion channel neurotoxin gene rBmK CTa. On this basis, it clones rBmK CTa into pEXSecI expression system to transfer in the BL21 (DE3), screens and obtains high-performance expressed bacterial strain, detects that the expressed product of the rBmK CTa accounts for 19.936% of the all-bacterium protein by SDS-PAGE electrophoresis, and by affinity chromatography, obtains purer protein with bioactivity, and can obtain 2.4mg protein from one liter culture liquor by purifying. The obtained modified recombinant scorpion chlorine ion channel neurotoxin has inhibition effect on neuroglia cell and can be used in preparing medicines curing diseases by inhibiting neuroglia cell and also be used in research on the space structure and pharmacological activity of scorpion neurotoxin.

The invention belongs to the field of research and development of polypeptide medicines and discloses a scorpion venom heat-resistant synthetic peptide and application thereof. An amino acid sequence of an SVHRP (scorpion venom heat-resistant peptide) is detected out from BmK (Buthus martensii Karsch) which is a traditional Chinese medicine; according to animal experiment verification, a scorpion venom heat-resistant peptide extract liquid sample has pharmacological activity in prevention and treatment of intractable epilepsy, Parkinson's disease and Alzheimer's disease, the sample is subjected to LaGm composite and repeated fast magnetic separation prior to nanoLC-ESI-MS (nano-liter reversed-phase chromatography and electrospray ionization mass spectrometry) integrated mass spectrometry parallel experiment to detect out a polypeptide sequence formed by 15 amino acid residues. The scorpion venom heat-resistant synthetic peptide is prepared by solid-phase chemical synthesis, chromatography purification and mass spectrometry identification. An amino acid sequence of the scorpion venom heat-resistant synthetic peptide is as shown in SEQ ID NO.1 and keeps pharmacological activity and safety of the scorpion venom heat-resistant peptide, and the scorpion venom heat-resistant peptide also has a characteristic of biological activity in promotion of reverse differentiation of neuroglial cells into neural stem cells.

The invention provides an application of 3-hydroxy fatty acid and derivatives thereof in the preparation of calcium ion channel regulator. An in vitro test indicates that the calcium ion channel regulator promotes neuroglia cell growth and activates cell calcium ion channel; and can be used for treating disease correlated to insufficient activation of the calcium ion channel, and used for culturing cell in vitro, particularly neuroglia cell.

The invention relates to a method for inducing neural stem cells to be differentiated into neurons and astrocytes by umbilical cord mesenchymal stem cells. The method comprises the following steps: (1) culturing the third generation of human umbilical cord mesenchymal stem cells; (2) co-culturing double antibodies by using DF12 and 2% serum for 24 hours, and then carrying out flow cytometry; (3) co-culturing and inducing into neural stem cells by using 2% of serum, 2% of B27, DF12, 20 ng / mL of EGF, 20 ng / mL of BFGF, 10 [mu] M of Forskolin, 1 mM of IBMX and 35 ng / mL of dbcAMP, and then adding differentiation factors; (4) detecting expressions of markers of four neural stem cells, namely Netin, PAX6, SOX1 and SOX2, by using immunofluorescence and fluorescent quantitative PCR; and (5) detecting the expression of the glial cell marker GFAP and the neuron marker MAP-2 by using an immunofluorescence technology and a fluorescent quantitative PCR technology. According to the invention, multiple factors are used in a combined manner, the addition amount is optimized, neurons and astrokeratinocytes can be differentiated at the same time, the marker is highly expressed, and the induction rate of umbilical cord mesenchymal stem cells to induce neural stem cells is improved, so that the neural stem cells can be obtained to be used for treating neuronal injury diseases.

The present invention is directed to a method of assessing in vivo human glial cell response to pathogenic infection that involves providing a non-human mammal either with at least 30% of its glial cells in its corpus callosum being human glial cells and / or with at least 5% of its glial cells its brain and brain stem white matter being human glial cells, subjecting the non-human mammal to pathogenic infection and assessing the in vivo human glial cell response to pathogenic infection. A method of identifying therapeutic agents for the pathogenic infection as well as forms of the non-human mammal having a pathogenic brain infection are also disclosed.

The invention provides an in-vitro artificial reflex arc structure and a construction method and application thereof, and belongs to the technical field of tissue engineering. The in-vitro artificialreflex arc structure which is clear in neuron network structure and high in signal propagation reliability is constructed in vitro by combining the advantages of high structural precision of a micro-protein pattern method based on micro-contact printing and stable formation of cultured synaptic connection; neuron axon extension is restrained and guided by utilizing a one-way threshold unit micro-protein mask pattern, so that the threshold value and direction of signal propagation in the in-vitro artificial reflex arc structure are controllable; micro-contact printing is carried out by adoptinga micro-mechanical arm, so that the requirement on the operation method is reduced, and the protein pattern is stable in formation; and the characteristic that the one-way threshold unit micro-protein mask pattern allows growth of dense neuron cell populations is utilized, so that an additional neuroglial cell layer does not need to be added to serve as a nutrient supporting layer of neurons during culture, the culture requirement of the in-vitro artificial reflex arc structure is greatly reduced, and the culture process is simplified.

The present invention relates to novel proteins, referred to herein as amidated glial cell line-derived neurotrophic factor (GDNF) peptides (or “Amidated Dopamine Neuron Stimulating peptides (ADNS peptides)”), that are useful for treating brain diseases and injuries that result in dopaminergic deficiencies.

The invention provides a treatment device for treating an Alzheimer's disease (AD). The treatment device for treating the AD comprises a collection module, a control module and a stimulation module; the collection module is constructed for collecting brain waves; and the control module is constructed for receiving corresponding data coming from the collection module to determine whether the brainwave of a user is in a specified state, and if not, a stimulation device is triggered; and the stimulation module is constructed for manufacturing an external stimulation to cause the brain waves to enter the specified state. The treatment device for treating the AD can effectively reduce the accumulation of A beta amyloid protein in AD patients, activate microglial cells, reduce nerve entanglement, and strengthen the brain wave (especially gamma brain waves) of a patient, has better effects on treating, relieving and inhabiting the AD, and can effectively improve the cognitive ability and memory ability of the patients.

The invention provides molecular tools to visualize, isolate, and manipulate the glial cells that are necessary for the formation, stability, and function of the synapse. The inventors identified a unique gene expression signature that distinguishes perisynaptic Schwann cells from all other Schwann cells. Using a combinatorial approach and coëxpressing two different fluorescence proteins, each using a different promoter, only those glial cells associated with the neuromuscular synapse are labeled.

Delivery of glial cell line-derived neurotrophic factor (GDNF) has provided benefits to Parkinsonian patients and is currently being tested in a Phase 1 / 2a clinical trial for ALS patients. However, chronic trophic factor delivery prohibits dose adjustment or shut off in the event of side effects. To address this, the Inventors engineered a stably integrating, third-generation doxycycline-regulated vector, allowing inducible and reversible expression of a therapeutic molecule Human iPSC-derived neural progenitors were stably transfected with the vector, expanded and transplanted into the adult mouse brain. The Inventors observed that the addition and withdrawal of doxycycline led to GDNF expression that could be induced and reversed multiple times, demonstrating that doxycycline can penetrate the graft and regulate transgene expression in vivo. The Inventors' findings provide a proof of concept for combining gene and stem cell therapy for effective modulation of ectopic protein expression in transplanted cells.

The invention provides a triterpenoid saponins compound, the molecular formula of which is C52H84O20 and the chemical name of which is 3b-O-[b-D-xylopyranose-(1-3)-a-L-rhamnopyranosyl-(1-2)-[b-D-glucopyranesyl-(1-4)]-a-L-arabopyranose] oleanolic acid (3b-O-[b-D-xylopyranosyl-(1-3)-a-L-rhamnopyranosyl-(1-2)-[b-D-glucopyranosyl-(1-4)]-a-L-arabinopyranosyl]oleanolicacid). An in-vitro antitumor test proves that the triterpenoid saponins compound has obvious inhibitory action on C6 rat spongioblastoma cell and four spongioblastoma cells: U87MG, U251MG, BT325 and SHG44, but has no influence on the growth of primarily cultured human neurogliocyte. The triterpenoid saponins compound can be used for preparing medicaments for treating glioma.