30 results about "Oligodendroglia Cell" patented technology

The invention belongs to the technical field of biomedical materials, and particularly relates to astragaloside-loaded conductive hydrogel as well as a preparation method and application thereof. The preparation method comprises the following steps: uniformly mixing a methylacrylic anhydride gelatin aqueous solution with an organic solvent solution of astragaloside, and carrying out ultraviolet light cross-linking curing to form methylacrylic anhydride gelatin / astragaloside hydrogel; soaking the obtained hydrogel in hydrochloric acid containing a free radical initiator; then soaking and polymerizing in an aniline ethanol solution; and soaking and purifying to obtain the methylacrylic anhydride gelatin-polyaniline conductive hydrogel loaded with astragaloside. In-vitro experiments prove that the compound has a certain anti-inflammatory effect, can induce neural stem cells to be directionally differentiated into neurons and oligodendrocytes, and is beneficial to promoting nerve regeneration and myelin sheath formation; finally, in-vivo experiments prove that the composition can improve the athletic ability and tissue function recovery of SCI rats, and has a good application prospect.

The invention belongs to the technical field of biological medicine, and particularly relates to a single-domain antibody VHH-L1 targeting LINGO-1 protein, and the amino acid sequence of the single-domain antibody VHH-L1 is shown as SEQ ID NO: 1. The single-domain antibody has nanomole-level high affinity and excellent specificity, can effectively block the interaction between LINGO-1 and ligands thereof, and remarkably promotes differentiation and myelination of oligodendroglia cells. The invention further provides a neural stem cell subjected to genetic engineering modification, and the neural stem cell can stably and continuously secrete the single-domain antibody VHH-L1. In a spinal cord injury animal model, the engineered stem cell shows an excellent treatment effect, can significantly promote motor function recovery, axon regeneration and myelin sheath repair, and effectively inhibits glial scar formation. The double advantages of cell therapy and long-acting protein delivery are fused, and a brand new efficient treatment strategy is provided for demyelination diseases such as multiple sclerosis and spinal cord injury.

A method of generating oligodendroglial progenitor cells and pre-myelinating oligodendrocytes is disclosed. Uses of the cell populations are further described.

Compositions comprising a population of oligodendrocyte progenitor cells (OPCs), as well as methods of making and using the same, are provided. In one aspect, a container comprising a composition, where the composition comprises a population of cells comprising a plurality of OPCs, and where the population of cells comprises less than 15% undesirable cell types is provided. In another aspect, the population of cells comprises less than 15% undesirable epithelial lineage cells. In yet another aspect, the population of cells comprises less than 2% K7 positive cells. In an aspect, a population of cells comprising a plurality of oligodendrocyte progenitor cells is capable of forming less than one epithelial cyst per 100,000 cells in a cyst assay is provided. An even further aspect of the present disclosure is a container comprising a composition, where the composition comprising a plurality of oligodendrocyte progenitor cells is useful in treating treat stroke, spinal cord injury, and multiple sclerosis.

In nerve diseases, cell dysfunction due to amyloid aggregate accumulation in nerve cells has attracted attention, but dysfunction of nerve axons responsible for neurotransmission is also considered to be one of the causes. However, no therapeutic agent that focuses on the repair and maintenance of nerve axons has been found. An object of the present invention is to provide a therapeutic agent that activates oligodendrocytes having a function of preserving nerve axons.SOLUTION: Transcriptome analysis with a psychotropic drug is carried out using an oligodendrocyte marker as an indicator, and it is found that the combined use of DPZ and NFN characteristically increases the expression of a transcriptional factor OLIG1 inducing the differentiation-maturation of the oligodendrocyte. Moreover, the drug concentration at this time was much lower than the expected clinical dose. The combined use of NFN and DPZ was observed to improve spatial memory in the mouse Y-maze test. The combination of NFN and DPZ can provide a novel treatment for cognitive and memory functions associated with neurological disorders.SELECTED DRAWING: None

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.

The application belongs to the technical field of biological drugs, and particularly relates to a preparation method of genetically modified human bone marrow mesenchymal stem cells and application thereof in treating nervous system diseases, in particular, multiple sclerosis. The human bone marrow mesenchymal stem cells are double-modified by brain-derived neurotrophic factor (BDNF) and anti-S1PR5 nanobody, so that the activity of the human bone marrow mesenchymal stem cells is improved, the survival of neurons or oligodendrocytes is promoted, cell apoptosis is inhibited, and myelin regeneration is promoted, and the human bone marrow mesenchymal stem cells can be applied to nervous system diseases, in particular, multiple sclerosis.

The invention provides a pathogenic factor for neurodegenerative diseases and application of the pathogenic factor. The pathogenic factor for the neurodegenerative diseases is a PASP-GPR37-IL-6 signal axis. According to the application, the action mechanism of the PASP-GPR37-IL-6 signal axis serving as a neurodegenerative disease (especially Parkinson's disease) pathogenic factor is defined for the first time, the molecular path of neuroinflammation and neurodegenerative diseases regulated and controlled by the oligodendroglia through the signal axis is disclosed, and the research blank of participation of the oligodendroglia in PD pathogenesis in the prior art is filled.

This invention describes artificial expression constructs for regulating gene expression in target types of central nervous system cells. By using the artificial expression constructs of this disclosure, it is possible to express or modify the expression of synthetic genes in spinal motor neurons, including SpP1 spinal motor neurons, Parg spinal motor neurons, Ogdh1 spinal motor neurons, and ChAT spinal motor neurons; α motor neurons, including Chodl spinal motor neurons; γ motor neurons; spinal excitatory motor neurons, including Mafa excitatory neurons, Esrrg Trhr excitatory neurons, and Slc17a6 spinal excitatory neurons; spinal inhibitory neurons, including Slc6a5 spinal inhibitory neurons; whole spinal neurons, including Esrrg spinal motor neurons and types of neurons found throughout the spinal cord; cerebrospinal fluid contact neurons, including Poln spinal motor neurons; and non-neuronal cells of the spinal cord, including astrocytes and oligodendrocytes.

The invention relates to a multi-system atrophic animal model with abnormal blood pressure regulation and a construction method of the multi-system atrophic animal model, and belongs to the technical field of biology. The invention provides a construction method of a multi-system atrophy animal model with abnormal blood pressure regulation, and the construction method comprises the following steps: injecting recombinant adeno-associated virus of alpha-synuclein specifically expressed by oligodendroglia cells into a target brain region of an experimental animal to obtain the multi-system atrophy animal model, the multi-system atrophy modeling target brain region is a medulla oblongata head end abdominal lateral region. Researches prove that the animal model constructed by using the construction method can replicate the performance of upright hypotension in multi-system atrophy, and has typical pathological characteristics and behavior characteristics of multi-system atrophy. Therefore, the construction method and the constructed animal model have wide application prospects in research of multi-system atrophy and screening of related therapeutic drugs.

Provided is a differentiation agent consisting essentially of SOX9 for generating oligodendrocyte progenitor cells (OPCs) from pluripotent stem cells (PSCs). Also provided are methods of generating PSCs and methods of using PSCs to generate OPCs and oligodendrocytes.SOLUTION: A method comprising culturing pluripotent stem cells (PSCs) to produce a population of cells comprising oligodendrocyte progenitor cells (OPCs), wherein the PSCs express engineered nucleic acids encoding SOX9 at a level sufficient to differentiate the PSCs into OPCs in the absence of other transcription factors encoded by the engineered nucleic acids.SELECTED DRAWING: Figure 2C

The invention relates to the field of biomedicine, in particular to a mouse oligodendroglia precursor cell culture method which mainly comprises the following steps: taking cerebral cortex tissues of a 3-day-old mouse, cutting the cerebral cortex tissues into pieces, digesting the cerebral cortex tissues to obtain mixed glial cells, and inoculating and culturing the mixed glial cells; and after culturing for 10 days, carrying out mechanical oscillation on a shaking table (the rotating speed is 250rpm, and the time is 6 hours), and separating to obtain the oligodendrocyte precursor cells with high purity and high activity. The method is easy and convenient to operate and high in repeatability, a large number of mouse oligodendroglia precursor cells can be obtained only through a conventional, simple and cheap culture medium, and the cells have the continuous multiplication capacity, can be continuously passaged and have the capacity of being differentiated into mature oligodendroglia cells; the method can be widely applied to in-vitro research of special physiological functions and related biological mechanisms of the mouse oligodendrocyte precursor cells.

Disclosed is a protein comprising no more than three human autoantigenic proteins, wherein a first human autoantigenic protein comprises a truncated myelin oligodendrocyte glycoprotein (MOG) amino acid sequence, a second human autoantigenic protein comprises a myelin basic protein (MBP) amino acid sequence, and a third human autoantigenic protein comprises a truncated proteolipid protein (PLP) amino acid sequence. Also disclosed are related nucleic acids, pharmaceutical compositions, methods of treating a demyelinating disease, and methods of producing the proteins.

The present application relates to the technical field of gene detection, in particular to a gene panel, method, device and use for somatic cell variation detection of SLC35A2 gene. The present application provides a gene panel, which can target capture the entire SLC35A2 gene related region, including exons, introns, promoters and enhancers, and carry out somatic cell variation detection, including SNVs, small Indels and SVs. The panel is used for detection of refractory epilepsy surgical brain tissue specimens, and can genetically diagnose mild cortical dysplasia with oligodendrogliosis epilepsy (MOGHE). This kind of disease is a new subtype of focal cortical dysplasia newly included by the International League Against Epilepsy in 2022. The panel has high variation detection rate and more comprehensive variation detection types.

A method of differentiating nonhuman primate induced pluripotent stem cells (iPSCs) to oligodendrocytes is provided. The method may include providing a modified vector comprising a piggyBac vector backbone that expresses one or more differentiation factor genes, including SOX10, OLIG2, and NKX6-2. The piggyBac vector backbone may comprise one or more terminal inverted repeats and one or more transposase recognition sites configured to interact with a piggyBac transposase to mediate genomic integration at TTAA or noncanonical target sequences. The vector may further include a selectable marker and a promoter for regulated expression. The modified vector may be introduced into nonhuman primate iPSCs, for example from Macaca fascicularis, by electroporation and used in a feeder-free differentiation workflow. The resulting differentiated cells may be identified by expression of oligodendrocyte-associated markers including O4, O1, PDGFRA, MOG, GALC, CNPase, and myelin basic protein (MBP).

A method of generating oligodendroglial progenitor cells and pre-myelinating oligodendrocytes is disclosed. Uses of the cell populations are further described.

The present disclosure relates to targeted bispecific transferrin receptor 1 (TfR-1) antibodies and methods of use thereof. In particular, provided herein are oligodendrocyte- and neuron-targeting bispecific TfR-1 antibodies and methods of use thereof.

A method of generating human mature oligodendrocytes is disclosed. The method comprises contacting a cell population which comprises human pre-oligodendrocytes with an inhibitor of the MAPK / ERK pathway under conditions that allow the pre-oligodendrocytes to differentiate into mature oligodendrocytes. Use of the MAPK / ERK pathway inhibitor for treating diseases is also disclosed.

The present invention relates to use of slow-releasing hydrogen sulfide organic donor ADT-OH drugs in the differentiation of neural precursor cells. ADT-OH can induce more directed differentiation of neural precursor cells into neurons and oligodendrocytes and less differentiation into astrocytes, promote the axon growth of neurons, and reduce the death of neural precursor cells, thereby providing a direction for the transplantation of neural precursor cells to repair damaged nerves. ADT-OH will likely become a new drug target for the clinical treatment of nervous system diseases.

Methods for generating pre-oligodendrocyte progenitor cells (pre-OPCs) and oligodendrocyte progenitor cells (OPCs) from human pluripotent stem cells are provided using chemically-defined culture media that allow for generation of pre-OPCs and OPCs in as little as three days. Culture media, isolated cell populations and kits are also provided.

The present application relates to nerve growth factor inducible protein or its gene in the preparation of treating spinal cord injury drug application. The present application proves that the lentivirus of overexpressing nerve growth factor inducible protein gene can promote the regeneration of oligodendrocytes, and then can effectively improve the recovery of motor function of spinal cord injury animal model through cell experiment and animal experiment.

Provided herein is a differentiation agent that consists essentially of SOX9 for the production of oligodendrocyte progenitor cells (OPCs) from pluripotent stem cells (PSC). Also provided herein are methods of producing the PSCs and methods of using the PSCs to produce OPCs and oligodendrocytes.

The invention belongs to the technical field of biology, and particularly discloses an exosome obtained by differentiation of embryonic stem cells, a preparation method of the exosome and application of the exosome in products. Compared with a traditional anti-aging cosmetic, the cosmetic developed by utilizing the exosome containing the oligodendroglia cells and the astroglia cells differentiated from the embryonic stem cells has higher bioavailability and better permeability, bioactive molecules can be more effectively transmitted, regeneration and repair of skin cells can be promoted, the skin aging phenomenon can be remarkably improved, and the cosmetic has a good application prospect. For example, skin moisture content is increased, skin elasticity is improved, and wrinkles are reduced.

Provided herein is a differentiation agent that consists essentially of SOX9 for the production of oligodendrocyte progenitor cells (OPCs) from pluripotent stem cells (PSCs). Also provided herein are methods of producing the PSCs and methods of using the PSCs to produce OPCs and oligodendrocytes.

Relapsing remitting multiple sclerosis (RRMS) is the most common form of multiple sclerosis, affecting more than 80% of MS patients. RRMS is comprised of two phases: the auto-inflammatory episodes, in which the immune system is actively destroying myelin, alternate with remission phases. Currently there is no cure for this devastating disease. The present disclosure provides compositions and methods useful for inducing remyelination. The methods are useful for promoting remyelination to treat diseases and disorders such as MS. The present disclosure describes compositions and methods useful for inhibiting LRP1 activity. In one aspect, a siRNA against LRP1 can be used. It is disclosed that myelination can be regulated by inhibiting the interaction of LRP1 and p75NTR and that it inhibits activation of Rho-A.

The invention relates to the field of senescence and systematic dynamics research, in particular to a glial cell marker set of a brain senescence critical point and application of the glial cell marker set in senescence mechanism research. 45 healthy human brain samples of 29-94 years old are analyzed through a single cell transcriptome, it is found for the first time that 56-60 years old are brain aging critical points, and a dynamic network marker (DNB) set composed of microglial cells, astrocytes and oligodendrocytes is identified and comprises key molecules mTOR, PADI2, JAK1, ARHGEF11 and KAZN. The marker set realizes early warning of an aging critical point by detecting the following characteristics: (1) PASP-GPR37L1 / PASP-GPR37 communication between glial cells is obviously weakened; (2) the activity of the neuron-microglial cell CX3CL1-CX3CR1 / IL34-CSF1R pathway is reduced, and the activity of the neuron-microglial cell pathway is reduced; and (3) DNB molecular expression fluctuation peak. The marker set disclosed by the invention can be used for developing a brain aging early warning kit and screening intervention targets.

The invention discloses a research method of a DNA (Deoxyribose Nucleic Acid) methylated transferase regulation mechanism of oligodendrocyte myelin sheath abnormality, and belongs to the technical field of detection research. The method comprises the following steps: S1, constructing a gene knockout mouse and a gene overexpression mouse through a gene editing technology, and setting a normal mouse as a control group; s2, separating and culturing the oligodendroglia cells; and S3, detecting the activity of the methylated transferase, the DNA methylation level and the myelin sheath index of the oligodendroglia cells. The invention focuses on a brand-new research method of a DNA methylated transferase regulation mechanism aiming at oligodendrocyte myelin sheath abnormality, and aims at deeper and more accurate analysis of the regulation mechanism by taking a mouse as an experimental model. According to the method, advanced molecular biology technology, cell biology technology and bioinformatics analysis means are integrated, and a set of comprehensive and systematic solution is provided for related research.

To provide induction of neural progenitor cells, oligodendrocyte progenitor cells, and oligodendrocytes by stem cell differentiation using landmark transcription factors.SOLUTION: Novel methods of inducing human iPSC-derived neural progenitors, oligodendrocyte progenitors, oligodendrocytes with unprecedented efficiency and functionality. The core of the present invention is the use of experimentally discovered transcription factors in a previously unknown manner at key differentiation decision points along the pathway from pluripotency to ectoderm to neuroectoderm to NPCs to OPCs to oligodendrocytes.SELECTED DRAWING: None

The invention relates to the technical field of neuroscience, in particular to a method for marking a new myelin sheath in a central nervous system, which comprises the following steps: constructing an ENPP6-P2A-CreERT2-T2A-CFP gene segment, and obtaining an ENPP6-CreERT2 knock-in mouse through a gene editing technology; the ENPP6-CreERT2 mouse and the mT / mG report mouse are subjected to mating, and ENPP6-CreERT is obtained; an mT / mG double transgenic mouse; carrying out tamoxifen induction treatment on the double transgenic mice in a target time period, and activating Cre recombinase; brain tissues are collected after induction, and marked middle-stage oligodendroglia cells and myelin sheath structures formed by the middle-stage oligodendroglia cells are observed through a fluorescence report system. According to the invention, the purpose of specifically marking new myelin sheath during tamoxifen induction is achieved. And a new research tool is provided for controlling new myelin sheath in a specific time period. The problems that all new myelin sheaths after induction start can be marked in an existing method, and the new myelin sheaths in the induction period cannot be specifically marked are solved.

A method is provided for producing oligodendrocyte-like cells, including (A) increasing abundances of oligodendrocyte transcription factor 2 (OLIG2) mutant and SRY-box transcription factor 10 (SOX10) in human pluripotent stein cells and (B) culturing the human pluripotent stem cells in which the abundances of the OLIG2 mutant and the SOX10 are increased and consequently differentiating the human pluripotent stem cells into oligodendrocyte-like cells, in which the OLIG2 mutant lacks a serine residue of wild-type OLIG2 at position 147, or the serine residue of the wild-type OLIG2 at position 147 is substituted with an amino acid other than serine.