126 results about "Astrocyte cells" patented technology

The invention discloses a bipeptide modified bionic nano-vesicle as well as a preparation method and application thereof, and belongs to the field of biological medicines. The dipeptide modified bionic nano-vesicle comprises nano-particles formed by PLGA (poly (lactic-co-glycolic acid)), and the nano-particles are loaded with a medicine with a nerve protection or nerve repair effect; the surface of the nanoparticle is coated with a macrophage membrane for expressing RVG peptide and T7 peptide. The bipeptide modified bionic nano-vesicle simultaneously presents T7 peptide and RVG peptide through an engineered macrophage membrane, the T7 peptide is combined with a blood-brain barrier transferrin receptor through high affinity to realize efficient brain entry, astrocytes in the brain are specifically recognized by virtue of the RVG peptide, accurate recognition and delivery of target cells in a focus area are realized, and the bipeptide modified bionic nano-vesicle has a good application prospect. Meanwhile, the natural inflammation tropism and immune escape ability of a macrophage membrane are reserved, and the problems that a traditional drug delivery system is low in targeting precision, and cross-barrier distribution and intracerebral distribution are difficult to cooperate are solved.

The invention discloses a construction method of a conditional knock-down dynactin animal model of astrocytes and an application of the animal model of the conditional knock-down dynactin animal model of the astrocytes. According to the method, a Dctn1LoxP gene knock-in mouse is hybridized with an Aldh1l1-Cre / ERT2 transgenic mouse, a target genotype mouse is obtained through three rounds of breeding, 100mg / kg Tamoxifen is continuously injected into the intraperitoneal cavity of the 2-month-old mouse for 5 days, and specific knock-down of dynactin in brain and spinal astrocytes is realized, including knockout of p150Glue and reduction of DCTN4, p50 and Arp1alpha protein levels. The model has the advantages of being high in specificity, permanent in intervention aging and capable of covering multiple life stages, the defects of a traditional model are overcome, the model can be used for researching the influence of dynactin on astrocyte neurobiological functions, a reliable tool is provided for screening related targets of nervous system diseases, and the model has important application value.

The application discloses application of T1R3 agonist sucralose in relieving Alzheimer's disease and related cognitive impairment, and aims at brain glucose metabolism disorder and cognitive decline problem, and the application takes sucralose as the only pharmaceutical active ingredient, corrects brain glucose metabolism disorder through targeting brain astrocyte sweet taste receptor T1R3, and then treats and relieves neurodegenerative diseases. The application is proved by animal experiments that cognitive dysfunction of AD model mice can be improved in a full range of molecular mechanisms, cell functions, tissue metabolisms and whole behavior, and a variety of dosage forms and medication strategies can be selected, and the application has good in-vivo safety and clinical transformation potential.

Synthetic nucleic acids are described that can be used for astrocyte-directed expression of heterologous nucleotide sequences, as well as methods of using same for astrocyte-directed expression of such nucleotide sequences for the treatment of neurodegenerative diseases.

The invention discloses a method for constructing astrocytes serving as a smoke disease model, and belongs to the technical field of crossing of stem cells and neuroscience. The method comprises the following steps: S1) reprogramming CD34 + cells in in-vitro PBMCs (peripheral blood mononuclear cells) of smoke disease patients carrying and not carrying RNF213p.R4810K mutation to obtain induced pluripotent stem cells; and S2) directionally inducing and differentiating the induced pluripotent stem cells into astrocytes through a neural progenitor cell way, wherein the obtained astrocytes are the astrocytes capable of being used as the smoke disease model. The astrocyte model prepared by the invention can be used for researching pathogenesis, nerve-blood vessel interaction process and blood-brain barrier (BBB) related functions of smoke diseases, and can be further applied to molecular typing of diseases and in-vitro function evaluation of candidate drugs.

The invention belongs to the technical field of medicines, and relates to injectable piezoelectric hydrogel for a spinal cord injury part as well as a preparation method and application of the injectable piezoelectric hydrogel. According to the hydrogel, methacrylated gelatin is used as a carrier, and a piezoelectric material MOF (at) PDA (at) M0, namely MP (at) M, of an enveloping porous structure is loaded in the hydrogel. The hydrogel can achieve dual functions under the ultrasonic action: (1) MP (at) M has piezoelectricity, ultrasonic mechanical energy is converted into electrical stimulation, calcium ion inward flow of astrocytes is triggered, mitochondria is promoted to be transferred from the astrocytes to neurons, and the mitochondrial function of the neurons is recovered; (2) the CD73 enzyme carried by the microglial cell membrane coated on the surface of the MP (at) M can degrade pro-inflammatory ATP (adenosine triphosphate) at the damaged part to generate adenosine, so that astrocytes are promoted to release lactic acid, and rapid energy support is provided for neurons. Mitochondrial transfer and energy supply are synchronously promoted through ultrasonic stimulation, neuronal plasticity is remodeled, spinal cord axon regeneration is promoted, and a new strategy is provided for spinal cord injury treatment.

This invention discloses a method for constructing a three-dimensional in vitro blood-brain barrier model with barrier function and its application, belonging to the biomedical field. The method includes: preparing a light-controlled biofunctionalized hydrogel with methacrylamide gelatin as the main framework; preparing a suspension of neurovascular matrix components using astrocytes and neurons; uniformly mixing the light-controlled biofunctionalized hydrogel and the neurovascular matrix component suspension to obtain a homogeneous cell-hydrogel composite solution, and preparing it into three-dimensional hydrogel microspheres; transferring the three-dimensional hydrogel microspheres to the bottom of a Transwell culture dish insert to form a stable neurolateral matrix layer; and adding a suspension of brain microvascular endothelial cells into the lower chamber of the Transwell culture dish. This invention achieves the synergistic effect of multiple bioactive substances, overcoming the shortcomings of the single bioactive substance loading method in the prior art.

The invention provides a polypeptide simulating Ascl1 and application thereof, and relates to the technical field of biomedicine, and the technical key point is that the polypeptide simulating Ascl1 is provided, the polypeptide is a TAT-Ascl1-EL-1 polypeptide, and the sequence of the TAT-Ascl1-EL-1 polypeptide is as shown in SEQ ID: NO 01. According to the application, through a verification experiment, the TAT-Ascl1-EL-1 polypeptide is successfully screened out, and in vitro, the polypeptide can be used for effectively reprogramming rat spinal cord reactive astrocytes into neuron-like cells; and a new selectable way is provided for the medical research on cell replacement treatment and cell regeneration after SCI.

The present application belongs to the field of biomedical technology, and particularly relates to a cell-derived extracellular matrix and a preparation method and application of a cell culture plate coated with the cell-derived extracellular matrix. The present application cultures human astrocytes in a cell culture plate, and makes the human astrocytes secrete extracellular matrix. After the human astrocytes are added into a cell lysate for cell removal treatment, nucleic acid fragmentation treatment is performed to obtain the cell-derived extracellular matrix. The present application has relatively simple operation, short time period, and can realize batch production of extracellular matrix without external virus carrying and stable components. The obtained cell-derived extracellular matrix is resistant to storage, has good stability, is highly similar to a natural brain environment when coated on a cell culture plate, has good biocompatibility with cells, can be applied to tissue repair and regeneration as an ideal biomedical material, can regulate the progress and efficiency of human dermal fibroblast HDF transdifferentiation into neurons, and can obtain in-vitro survival neurons.

Described herein are methods and compositions for treating a disease, e.g. cancer (including solid tumors), using glial cells (e.g. microglia cells and / or astrocytes) and / or macrophages (e.g., CNS-associated macrophages) infected with an oncolytic virus (e.g., vaccinia virus). The methods and compositions provided herein demonstrate a synergistic anti-cancer effect.

The invention belongs to the technical field of biological medicines, and relates to application of an HIF-1alpha inhibitor in preparation of a product for inducing transformation of astrocytes from a pro-inflammatory type to an anti-inflammatory type. The invention reveals that activation of an HIF-1 signal channel is an important mechanism for driving neuroinflammatory response and pro-inflammatory A1 type astrocyte formation, and inhibition of HIF-1 activation can effectively promote generation of neuroprotective A2 type astrocytes. By applying the HIF-1alpha small-molecule inhibitor KC7F2 to astrocytes, HIF-1alpha activation is blocked, and the astrocytes are promoted to be converted from a proinflammatory A1 phenotype to an anti-inflammatory A2 phenotype, so that inflammatory response is inhibited, neurotoxicity is reduced, and a neuron microenvironment is improved. The invention provides a novel intervention strategy based on HIF-1alpha signal regulation and control, and a novel theoretical basis and a novel potential drug treatment scheme are provided for treatment of nervous system injury and related neurodegenerative diseases.

Disclosed are means, methods, and compositions of matter useful for treatment of oncological indications through stimulation of protective anti-cancer immunity. In one embodiment the invention discloses the unexpected effect of astrocytes to augment immune stimulating activities of dendritic cells. In one embodiment dendritic cells are pulsed with tumor lysates and subsequently co-cultured with astrocytes in the presence of toll-like receptor agonists.

An application of Bone Marrow Mesenchyml Stem Cell Exosomes (BMSC-Exos) in treating Parkinson's disease (PD) is provided, wherein the BMSC-Exos are generated by stimulating BMSCs with a culture solution and extracted from the culture solution after passage; and the culture solution of the BMSCs is an α-MEM culture solution containing FBS and PS. The BMSC-Exos can greatly improve a motor function of a model mouse with PD, protect dopaminergic neurons of the model mouse with PD, improve an olfactory function of the model mouse with PD, and also inhibit the activation of olfactory astrocytes of the model mouse with PD.

The present invention relates to a composition comprising HAPLN1 as an active ingredient for preventing or treating senile degenerative brain diseases. Specifically, recombinant human HAPLN1 protein (rhHAPLN1) lowers the protein level of p16 in cultured human astrocytes to inhibit cellular senescence caused by the accumulation of beta amyloid peptides, and further inhibits phosphorylation (p-p38 MAPK) of p38 MAPK protein, thereby also having the possibility of inhibiting inflammatory responses associated with the onset of Alzheimer's disease and Parkinson's disease. In addition, the recombinant human HAPLN1 protein (rhHAPLN1) exhibits significant memory and learning improvement effects in in vivo experiments performed using a mouse acute Alzheimer's disease model, and thus can be expected to exhibit preventive and therapeutic effects against Alzheimer's disease that may occur with aging and the like. In addition, the inhibitory effect of the rhHAPLN1 protein on cellular senescence and inflammatory responses of astrocytes can provide a very important clue for establishing prevention and treatment strategies not only for aging itself but also for brain functions, motor behaviors, memory, seizures, dementia, brain tumors, and the like.

The present invention provides, in part, a protein-drug conjugate comprising an anti-fibroblast growth factor receptor 3 (FGFR3) (e.g., human FGFR3) antigen-binding protein (e.g., scFv, Fab) conjugated to a molecular cargo (e.g., a polynucleotide, a polypeptide, a liposome, or a lipid nanoparticle), for delivering the molecular cargo to a target tissue (e.g., the brain). Methods are provided for treating various diseases or disorders, such as neurological disorders, with the conjugate.

The invention belongs to the technical field of medicines, and particularly relates to preparation of CD73 positive NK cells of umbilical cord blood from different starting sources and application of the CD73 positive NK cells to treatment of Alzheimer's disease. The CD73 + NK cells differentiated from different initial cell types (CD34 positive cells, CD3 negative / CD56 positive cells and CD56 negative cells) of umbilical cord blood are studied, it is found that all the initial cell types of umbilical cord blood sources can be differentiated into the CD73 + NK cells, 34 +-73-NK cells show a higher growth rate, 56-73-NK cells show higher cytotoxicity, and the CD73 + NK cells can be differentiated into the CD73 + NK cells. And the overall effect of the 56-73-NK cell is superior to that of the 34 < + >-73-NK cell. Further research shows that the CD73 + NK can inhibit activation of STZ injection mouse hippocampal microglia and astroglia, so that the neuroinflammation of the hippocampal is reduced, and a new solution is expected to be provided for treatment of AD.

An object of the present invention is to provide a method of evaluating intercellular interactions in neuroinflammation using a co-culture containing human-derived neural cells capable of mimicking human brain functions. According to the present invention, there is provided a method of evaluating intercellular interactions in neuroinflammation, the method including a step of producing a co-culture containing at least two cells selected from the group consisting of human-derived astrocytes, human-derived neurons, human-derived microglia, and human-derived oligodendrocytes, a step of applying an inflammatory stimulation to a first cell contained in the co-culture, a step of detecting at least one selected from the group consisting of an inflammatory response marker in the cells contained in the co-culture, neural activity of the cells, and cell morphology, and a step of evaluating, over time, a change in at least one selected from the group consisting of the inflammatory response marker, the neural activity, and the cell morphology in the first cell and a second cell different from the first cell contained in the co-culture.

Ventricular catheters and their methods of use are disclosed. In some embodiments, the disclosed ventricular catheters may reduce, or substantially prevent, obstruction of the catheter by astrocytes or other brain tissue due to adhesion and / or growth within the catheter. For example, in some embodiments, the holes and internal lumen of a ventricular catheter may be constructed such that the wall shear stresses applied within the holes and internal lumen of the catheter are greater than a threshold shear stress to prevent cell adhesion and growth within the catheter.

The present application relates to the technical field of biotechnology, and particularly discloses a composition and a method for reprogramming astrocytes into functional neurons. The composition for reprogramming astrocytes into functional neurons comprises a compound PT109B. The composition for reprogramming astrocytes into functional neurons provided in the present application can reprogram astrocytes into functional neurons, and effectively solves the problems of a large number of small molecules and complicated steps in the current chemical reprogramming technology.

The present invention relates to a method for efficiently differentiating neural stem cells into astrocytes and, more particularly, to a cell conversion-based method for more efficiently differentiating human neural stem cells into astrocytes that exhibit immune response suppression ability within a short period of time. Unlike a conventional method, the method for differentiating neural stem cells into astrocytes by using a differentiation medium containing a combination of several cytokines, according to the present invention, involves a shortened differentiation time and has excellent differentiation efficiency, and the differentiated astrocytes exhibit immune response suppression ability, and thus can be useful as an agent for treating various brain diseases such as degenerative neurological diseases.

The application discloses a kind of astrocyte dynamic calcium event adaptive threshold segmentation method and device, it is related to cell calcium signal identification technical field, including: original video is carried out calcium signal enhancement denoising, constructs time sequence mask dynamic tracking calcium active event, based on Gaussian mixture model, gray distribution is fitted as multiple Gaussian components superposition and segmented estimation extracts active calcium signal, calculate highlight pixel proportion and interframe similarity index, adaptive dynamic update global threshold and local threshold, generate calcium signal image by window function transformation.Can be in high noise, low signal-to-noise ratio astrocyte calcium imaging video, effectively suppress random imaging noise and preserve weak signal, significantly improve the transient calcium event detection capability of astrocyte, adaptively identify the brightest active calcium signal peak, dynamically adapt the brightness distribution change of each frame image, stably and accurately segment out dynamic calcium event, robustness is strong, degree of automation is high.

Methods and compositions for manipulating metabolism in astrocytes to improve astrocytic and neuronal function, as well as individual pathology hallmarks and symptoms during the development of neurodegeneration by increasing PPARα expression and activity specifically in astrocytes within the central nervous system to treat a variety of neurodegenerative conditions including but not limited to conditions involving neuronal lipid dysregulation, oxidative damage, accumulation of β-amyloid or other protein aggregates, dementia, and motor dysfunction. Also provided are methods of treating peripheral metabolic dysfunction associated with neurodegenerative conditions.

The invention belongs to the technical field of cell culture, and particularly relates to a culture method and application of human astrocytes. According to the culture solution provided by the invention, DMEM (Dulbecco Modified Eagle Medium) and MCDB 131 are mixed according to a specific ratio to form a basic culture medium, and functional additives of HEPES, Glutamax, N2, G-5, B-27, hEGF (Human Epidermal Growth Factor) and the like with accurate concentration and fetal calf serum with proper concentration are matched. The culture solution can effectively improve the vitality and proliferation efficiency of SVGP12 cells, guarantees the growth stability and morphological consistency of the cells, can provide a high-quality and reliable cell source for the application of human astrocytes in the fields of neurobiology research, neurological disease mechanism exploration, drug screening and the like, and has important practical value.

This invention relates to mutants of the adeno-associated virus (AAV) capsid protein. Recombinant viral vectors carrying mutants of the AAV1 capsid protein can be used for the specific expression of the introduced gene in astrocytes at the site of spinal cord injury lesions.

The application discloses application of an S1PR1 selective agonist SAR247799 in preparation of a drug for treating neuromyelitis optica spectrum disorders. The SAR247799 can up-regulate S1PR1 expression of astrocytes, activate an S1PR1 signal path of the astrocytes, inhibit AQP4-IgG and complement-mediated damage of the astrocytes, reduce loss of AQP4, GFAP and ALDH1L1 in a lesion area of brain tissue of a neuromyelitis optica spectrum disorder model mouse, and relieve pathological damage of the neuromyelitis optica spectrum disorder model. In-vivo and in-vitro experiments prove that the SAR247799 can effectively inhibit AQP4-IgG and complement-dependent cytotoxicity effects and promote survival of the astrocytes. The application provides a novel, efficient and specific targeted drug for clinical treatment of the neuromyelitis optica spectrum disorder.

Artificial expression constructs for modulating gene expression in targeted central nervous system cell types are described. The artificial expression constructs can be used in the assessment and / or treatment of epileptic disorders.

This disclosure relates to adeno-associated virus variants capable of performing astrocyte-specific gene transfer. Administration of a recombinant viral vector containing nucleic acid encoding an AAV capsid protein mutant according to this disclosure enables the transfer and expression of therapeutic genes into specific astrocytes, thus demonstrating significant efficacy in the prevention or treatment of brain diseases.

The present invention relates to a method of generating an in vitro modular 3D brain tissue model (3D BTM) comprising: a. mixing 50,000 to 1,000,000 freshly splitted, single neurons (NE) and astrocytes (AS) or their precursor cells in a ratio of NE:AS = 1:3 to 10:1, followed by spinning down to introduce self-aggregation in low attachment conditions, without addition of exogenous matrices; b. treating cells obtained in step a. with a NOTCH signaling inhibitor for driving terminal neuron differentiation for at least 2 days; c. treating the cells obtained in step b. with at least one mitotic inhibitor to remove residual dividing cells for at least 3 days, thereby yielding a post-mitotic aggregated 3D culture of neurons and astrocytes; d. adding differentiated microglia (MG) to the culture obtained in step c. in a ratio of NE:MG = 1:1 to 20:1, to initiate migration of MG into the culture for 3-10 days; e. culturing the culture obtained in step d. in neuron media with addition of TGFβ1 and cytokines selected from the group comprising CSF1-R agonists to support microglia maintenance and proliferation for at least 2 weeks, thereby inducing formation of a modular in vitro 3D BTM culture.

A method for detection or monitoring status of traumatic brain injury (TBI) and / or spinal cord injury (SCI) in a subject is provided. In one embodiment, the method comprises contacting a specimen of bodily fluid obtained from the subject with reagents for assaying for a marker of TBI selected from aldolase C (ALDOC) and brain lipid binding protein (BLBP / FABP7), or a trauma-specific break down product (BDP) of ALDOC or BLBP / FABP7. The method further comprises measuring the amount of marker present in the specimen as compared to a control sample, and determining the presence of TBI or SCI when an elevated amount of marker is present in the specimen compared to the control sample. Optionally, the method further comprises measuring the amount of glutamine synthetase (GS), astrocytic phosphoprotein PEA-15 (PEA15), αB-crystallin (CRYAB / HSP27), a trauma-specific proteolytic cleavage product of ALDOC, GS, PEA15, or CRYAB, or any combination of two or more thereof.