1786results about "Nervous system cells" patented technology

The invention relates to the technical field of cytology, in particular to a grass carp brain astrocyte line and application thereof, the grass carp brain astrocyte line is preserved in China Center for Type Culture Collection on May 7, 2025, and the preservation number of the grass carp brain astrocyte line is CCTCC NO: C2025149. The grass carp brain astroglia cell line provided by the invention has the capability of efficiently proliferating GCRV-II, and the virus titer of the GCRV-II replicated in the cell line at least can reach 1.38 * 10 < 8 > pfu / mL or above; after the GCRV-II is blindly passed for 5 generations in a grass carp astroglia cell line, the grass carp can still have typical bleeding symptoms and death due to the virus. And the exogenous plasmid transfected grass carp brain astroglia cell line has similar transfection efficiency to commercial grass carp kidney cells. Therefore, the invention lays an important foundation for deep research of pathogenic mechanism of GCRV-II, vaccine preparation, antiviral drug screening and prevention and control of grass carp viral hemorrhagic disease.

A brain organoid containing optic vesicles generated based on H9 induction and an eye-brain fusion culture method thereof are provided. H9 embryonic stem cell induction is used to generate a brain organoid containing optic vesicles with primitive visual field. Based on an established optic vesicle brain organoid culture system, microscopic imaging is combined with specific marker antibodies related to early retinal development and photoreceptor cell maturation to structurally and functionally identify the brain organoid containing optic vesicles.

The invention relates to a cell collection method capable of simultaneously collecting three cells in a co-culture model, and belongs to the technical field of biology. The invention provides a cell collection method capable of simultaneously collecting three cells in a co-culture model, and the cell collection method comprises the following steps: after a three-cell co-culture model is constructed, taking out a Transwell chamber, retaining cells in the lower chamber, and collecting the cells in the lower chamber; respectively digesting the cells on the two sides of the Transwell cell membrane by using a trypsin solution with the concentration of 0.5 g / 100mL so as to respectively collect the cells on the two sides of the Transwell cell membrane. According to the cell collection method disclosed by the invention, the three cells in the three-cell co-culture model are simultaneously collected in a manner of digesting the cells on the two sides of the Transwell membrane step by step by using pancreatin, so that not only is the cell and consumable cost saved, but also the experimental synchronism of the three cells is ensured, and convenience is provided for optimizing the experimental process.

The invention discloses a bone organ chip loaded with a microelectrode array and a use method, and relates to the technical field of organ chips, the bone organ chip is made of a polydimethylsiloxane material, and the bone organ chip comprises a three-layer structure: a top layer, a middle layer and a bottom layer; the middle layer comprises two blood vessel micro-channels, two osteoblast micro-channels and a neuron micro-channel, the channels are separated through columns and micro-columns, and cell interaction in a bone micro-environment is simulated; a microelectrode array is arranged on the top layer and is used for monitoring electrical activity of neurons in real time; the bottom layer is provided with a pneumatic valve which can control opening and closing of the micro-channel. According to the invention, nerve and blood vessel channels are introduced, a nerve-blood vessel-immunoregulation bone microenvironment is constructed, physiological processes such as osteogenesis-blood vessel formation coupling and the like are embodied, intervals of different sizes can enhance intercellular crosstalk and allow blood vessels and neuron axons to selectively pass through, so that the chip can simulate a complex microenvironment of bone tissues, and the microenvironment of the bone tissues can be simulated; and an efficient and accurate in-vitro model is provided for bone disease mechanism research and drug development.

The invention relates to a retina nerve and blood vessel unit in-vitro three-culture model and a preparation method thereof, and belongs to the technical field of biology. The invention provides an in-vitro three-culture model of a retina nerve and blood vessel unit. The in-vitro three-culture model is obtained by carrying out in-vitro Transwell indirect co-culture on retina microvascular endothelial cells, retina ganglion cells and retina Muller cells. The in-vitro three-culture model of the retina nerve and blood vessel unit is based on a three-cell indirect co-culture method, retina microvascular endothelial cells, retina ganglion cells and retina Muller cells are simultaneously incorporated by utilizing Transwell, and the three cells are in indirect contact. The in-vitro three-culture model of the retina nerve and blood vessel unit can be used for more objectively simulating pathophysiological states of various cells of the retina nerve and blood vessel unit, so that common pathophysiological changes of mutual dependence and interaction of the three cells under in-vitro conditions can be observed.

Provided herein are engineered nucleic acids (e.g., expression vectors, including viral vectors, such as lentiviral vectors, adenoviral vectors, AAV vectors, herpes viral vectors, and retroviral vectors) that encode OCT4; KLF4; SOX2; or any combination thereof that are useful, for example, in inducing cellular reprogramming, tissue repair, tissue regeneration, organ regeneration, reversing aging, or any combination thereof in the central nervous system or ex vivo. Also provided herein are recombinant viruses (e.g., lentiviruses, alphaviruses, vaccinia viruses, adenoviruses, herpes viruses, retroviruses, or AAVs) comprising the engineered nucleic acids (e.g., engineered nucleic acids), engineered cells, compositions comprising the engineered nucleic acids, the recombinant viruses, engineered cells, engineered proteins, chemical agents that are capable of activating expression of OCT4; KLF4; SOX2; or any combination thereof, an engineered protein selected from the group consisting of OCT4; KLF4; SOX2; or any combination thereof, an antibody capable of activating expression of OCT4; KLF4; SOX2; or any combination thereof, and methods of treating a disease (e.g., a neurological disease), preventing a disease (e.g., neurological disease), regulating (e.g., inducing or inducing and then stopping) cellular reprogramming, regulating tissue repair, regulating tissue regeneration, or any combination thereof.

The invention provides preparation, sorting and application of LGE / CGE organoid and GABAergic neurons, and belongs to the field of brain organoid differentiation and GABAergic neurons. The preparation method of the LGE / CGE type organ comprises the following steps: S1, performing embryoid formation and initial culture on the 0th-4th day; s2, performing nerve induction and matrigel embedding on the 5th-11th day; s3, culturing the brain organoid on the 12th day to the 19th day; s4, dynamically culturing and screening the brain organoid on the 20th-35th day; and S5, carrying out differentiation and collection on LCOs of the LGE / CGE type organs after the 35th day. According to the method, the LGE / CGE organs containing the high-purity GABA energy neurons are obtained through differentiation from the brain organs for the first time, the high-purity LGE type GABA energy neurons and the high-purity CGE type GABA energy neurons are obtained through a specific sorting method, and the method has the deep application potential in the fields of disease model construction, medicine research and development and the like.

To provide novel transduction enhancers and uses thereof.SOLUTION: The present invention relates to a method for transducing a target cell, the method comprising the step of contacting a target cell with a retroviral vector and a compound capable of enhancing transduction efficiency or a combination of such compounds, wherein the target cell is pre- and / or co-stimulated by pre- and / or co-incubation with a transduction enhancing compound or a combination of transduction enhancing compounds prior to and / or during contacting the target cell with the retroviral vector.SELECTED DRAWING: None

The invention relates to the technical field of biology, in particular to a composition for preparing a brain organ, the brain organ and application of the brain organ. The invention further discloses a construction method of the brain organ, and on the basis of the method, different stem cells such as ESCs and iPSCs can be utilized to stably construct the three-dimensional brain organ model capable of simulating the medulla oblongata trigeminal nerve. The invention further discloses an organoid assembly which has important application potential in the fields of research on development, functions and related diseases of brain nuclei, drug discovery and the like.

The invention provides universally acceptable “off-the-shelf” hypoimmunogenic pluripotent cells and differentiated cardiac, endothelial, neuronal, islet, or retinal pigment cells thereof. Such hypoimmune cells are used to treat patients in need thereof. The cells lack major immune antigens that trigger immune responses and are engineered to avoid phagocytic endocytosis.

The invention discloses application of a CXCL14 combined immune checkpoint inhibitor in treatment of spinal glioma. The immune checkpoint inhibitor is selected from a PD-1 inhibitor or a combination of the PD-1 inhibitor and a CTLA4 inhibitor. In-vivo and in-vitro experiments prove that the CXCL14 combined with the PD-1 inhibitor, the CXCL14 combined with the PD-1 inhibitor and the CTLA4 inhibitor can be used for remarkably inhibiting the growth of mutant spinal glioma and have a remarkable synergistic effect. The invention provides a new strategy for treatment of spinal glioma, and is widely applied clinically.

The invention provides a marker of spinal cord functional neural precursor cells, a detection method and a sorting method, and belongs to the technical field of biological medicine. The invention provides application of a marker detection reagent in preparation of a kit for detecting spinal cord functional neural precursor cells. The invention further provides a sorting-based method for separating the SFNPCs cells, and the cells are sorted through the Marker of the specific SFNPCs, so that the cell purity of the SFNPCs is remarkably improved, the difference between batches is reduced, and a high-purity and homogeneous SFNPCs cell population is obtained. The survival rate of the SFNPCs cells separated and subcultured to the P9 generation by the method disclosed by the invention is more than 85%, and the SFNPCs cells have a good treatment effect on a spinal cord injury model.

Methods for differentiating pluripotent stem cells to neuroectoderm in dynamic suspension culture using small molecule or protein inhibitors of TGFβ / Activin / Nodal signaling and BMP signaling are provided. Also provided are methoc and protocols for differentiating pluripotent stem cells such as human embryonic stem cells first to neuroectoderm, then further to glial progenitor cells, and further to oligodendrocyte progenitor cells (OPCs), and compositions obtained thereby. The methods of the present disclosure reproducibly produce neuroectoderm progenitor cells by day 7 of the differentiation process, glial progenitor cells by day 21 of the differentiation process and OPCs by day 42 of the differentiation process.

Disclosed herein are compositions and methods related to differentiation of stem cells into pancreatic islet cells. In some embodiments, the methods provided herein relate to generation of pancreatic β cell, α cell, δ cells, and EC cells in vitro. In some embodiments, the disclosure provides pharmaceutical compositions including the cells generated according to the methods disclosed herein, as well as methods of treatment making use thereof.

The invention provides a human-derived recessive retinal degeneration disease organ-like model based on Prom1 gene knockout. Specifically, the invention provides a specific gRNA targeting a Prom1 gene exon 9, and the specific gRNA can be used for efficiently knocking out the Prom1 gene of the human embryonic stem cell. The invention also provides a Prom1 gene knockout stem cell line derived from the human embryo pluripotent stem cell H9 and a retinal organ disease model. The retina-like organ can provide a research model for clinical treatment drugs.

Provided are chemically modified silk fibroin and a use thereof in cell and organoid culture. The chemically modified silk fibroin is a product obtained by sequentially carboxylating silk fibroin and modifying same by an organic amine having a phenol group. Also provided is a hydrogel based on the chemically modified silk fibroin. A hydrogel system has a hierarchical structure and mechanical properties similar to those of an extracellular matrix, and exhibits characteristics such as definite composition, controllable physicochemical properties, low cytotoxicity, good biocompatibility, and biodegradability, can support the growth and differentiation of cells and organoids, and is suitable as a matrigel for cell and organoid culture.

The invention belongs to the technical field of biomedicine, and relates to a method for constructing a mouse embryo-derived hypothalamic organ model and application, the invention proposes that a mouse embryo is used for constructing a hypothalamic organ for the first time, and the mouse embryo has a definite development time sequence and genetic operability; the naturally retained vascular endothelial cells and multilineage precursor cells provide unique advantages for constructing a three-dimensional organ containing multiple nucleuses such as a preoptic region, a paraventricular nucleus, an arcuate nucleus and a supraoptic nucleus, and the model not only breaks through the nucleus coverage limitation of the existing iPSCs organ, but also can be used for constructing the three-dimensional organ containing multiple nucleuses such as the preoptic region, the paraventricular nucleus, the arcuate nucleus, the supraoptic nucleus and the like by reconstructing a nerve-blood vessel unit. High-fidelity simulation of complex physiological functions of the hypothalamus is realized, and an irreplaceable technical platform is provided for mechanism analysis of neuroendocrine diseases and high-throughput screening of drugs.

Methods for generating human vascular leptomeningeal cells (VLMCs) from human oligodendrocyte progenitor cells (OPCs) are provided using chemically-defined culture media that allow for generation of differentiated cells in a 34-day culture protocol. Methods of generating human VLMCs from human pluripotent stem cells using chemically-defined culture media in a 40 day culture protocol are also provided. Culture media, isolated cell populations, and kits are also provided.

This invention discloses a method for rapidly constructing a human-like cerebral cortex organ-on-a-chip using bio-3D printing and its applications. It comprises three parts: a microfluidic chip fabrication method, a human-like cerebral cortex hydrogel preparation method, and the printing of the human-like cerebral cortex. The microfluidic chip comprises five layers: a mixed-flow channel layer, a liquid pool layer, a micropore array layer, a human-like cerebral cortex culture layer, and a culture medium recovery layer. The human-like cerebral cortex hydrogel is composed of gelatin, alginate, and hyaluronic acid. The human-like cerebral cortex is directly printed into the microfluidic chip using a suspension bath extrusion printing method, and then encapsulated to obtain the human-like cerebral cortex organ-on-a-chip. This invention overcomes the shortcomings of traditional cell culture by directly constructing a large-scale human-like cerebral cortex with three interconnected layers in situ within the organ-on-a-chip using bio-3D printing. Perfusion culture mimics cerebrospinal fluid circulation, facilitating substance exchange, maintaining cell viability, and inducing cell differentiation, and can be widely used in drug development for brain diseases.

The invention discloses a preparation method of a cochlear organ chip integrated with a blood labyrinth barrier, and belongs to the field of biomedical engineering. The preparation method of the simulated blood labyrinth barrier comprises the following steps: constructing an endothelial cell culture cavity and a pericyte culture cavity, and separating the endothelial cell culture cavity and the pericyte culture cavity through a simulated basement membrane; and respectively inoculating percutaneous cells and endothelial cells into a percutaneous cell culture cavity and an endothelial cell culture cavity, and culturing to obtain the simulated blood lost barrier. The chip can effectively simulate the structure and the function of the BLB, and the barrier integrity of the BLB is evaluated through TEER (trans-epithelial electrical resistance) measurement and an apparent permeability coefficient. The invention also relates to application of the chip in NIHL drug screening, in particular to drug evaluation for oxidative stress induced inner ear organ injury. Through the platform, the protection effect of the candidate drugs on the TBHP-induced oxidative stress injury of the inner ear organs can be evaluated, and a new tool and thought are provided for developing novel NIHL treatment drugs.

The invention discloses a 3D (three-dimensional) visual bionic intestine-blood vessel-nerve interface organ simulation chip, which is characterized in that a micro-fluidic chip is used as a platform to construct an intestinal tract-blood vessel-brain system which simulates biological transformation of perfluorinated compounds in intestinal tracts under near physiological conditions and biologically transports the perfluorinated compounds through blood vessels; a neuronal cell culture chamber, a vascular endothelial cell culture chamber and an intestinal tract cell culture chamber are respectively arranged on the micro-fluidic chip, the culture chambers are communicated through micro-columns, and the vascular endothelial cell culture chamber serves as a barrier in the middle; perfluorinated compounds enter corresponding cell culture cavities for culture through reagent injection channels of different cell culture channels, generated metabolites are discharged through the channels, and multi-organ interaction and toxicity induced by the perfluorinated compounds are analyzed. The chip can simulate an intestinal barrier structure, a blood vessel and a neural network structure, can highly simulate biological transport and transformation of a perfluorinated compound between intestines and brains, and effectively reduces cost and time.

The present disclosure provides a method of producing a non-human mammalian animal model comprising human neural tissue, the method comprising introducing a first human neural organoid into a central nervous system location of a newborn non-human mammal; and allowing the newborn non-human mammal to mature to produce the non-human mammalian animal model comprising human neural tissue. The present disclosure provides a method of modeling a neuropsychiatric disorder. The present disclosure also provides a method of determining the effectiveness of a candidate agent on a neuropsychiatric disorder. The present disclosure provides a method for altering the behavior of a mammal. Also provided are non-human mammalian animal models comprising human neural tissue.

The invention discloses a fusion polypeptide TGNL and application of neural stem cells modified by the fusion polypeptide TGNL in spinal cord injury repair. The fusion polypeptide TGNL is composed of a TAT penetrating domain, a GSTP targeting domain, an NICDi inhibition domain, an MMP-2 activation domain and a flexible Linker connecting the three domains, and the full-length amino acid sequence is as shown in SEQ ID NO. 1. The invention also provides a preparation method of the polypeptide, a neural stem cell (hNSCs-TGNL) for expressing the polypeptide and a construction method of the neural stem cell (hNSCs-TGNL). Experiments show that the fusion polypeptide TGNL can efficiently penetrate nerve cells, specifically target glial scars, is selectively activated by MMP-2, and promotes neural stem cells to differentiate into neurons by inhibiting Notch signals; the hNSCs-TGNL has high survival rate and strong penetrability in an in-vitro glial scar model, and can significantly promote motor function recovery, reduce injury volume, increase axon density and reduce glial scars in a rat spinal cord contusion model. The invention provides a novel candidate drug and a cell treatment strategy for clinical treatment of spinal cord injury, and has remarkable clinical application value.

The invention discloses a brain glioma organ chip with adjustable tumor microenvironment gradient and a method for mediating formation of brain glioma organoid by the brain glioma organ chip, and belongs to the technical field of organ chips. The preparation method comprises the following steps: firstly, preparing a glioma organ chip with adjustable tumor microenvironment gradient by utilizing a prepolymer solution containing glioma cells and vascular endothelial cells and a prepolymer solution containing biochemical molecules; then, the obtained brain glioma organ chip with the adjustable tumor microenvironment gradient is subjected to three-dimensional dynamic co-culture under the perfusion condition, three-dimensional culture and co-culture of brain glioma cells and vascular endothelial cells are achieved at the same time, endothelial-glioma multicellular tumor spheres are formed, and construction of brain glioma organs is achieved. The brain glioma organoid established by the invention successfully summarizes key characteristics of a tumor microenvironment, including biophysical factors simulated by physiological fluid and biochemical factors of three-dimensional culture microgel with adjustable concentration gradient of biochemical molecules.

Provided herein are methods of expressing syntaxin-binding protein 1 (STXBP1) in a neuron. Also provided herein is a modified adeno-associated virus (AAV) encoding a STXBP1 under the control of a promoter operable in a brain cell or neuronal cell.

Disclosed are in vitro methods for the differentiation of precursor cells into a neural crest cell (NCC) primed to a neurogenic lineage. The methods may include, for example, the steps of activating a Hedgehog signaling pathway (“HH signaling pathway”) in a precursor cell, wherein the precursor cell may be contacted with a neural crest cell induction medium for differentiation of the precursor cell into a neural crest cell. Compositions for carrying out the disclosed methods are also disclosed.

The invention provides hindbrain organoids and methods of producing such organoids. Said hindbrain organoids may include healthy or healthy and diseased tissue. Also provided are methods of testing therapeutic agents using said hindbrain organoids. The invention also provides culture mediums used for producing (patterning) said hindbrain organoids and kits including the culture medias.

The invention discloses a method for inducing dorsal root node satellite glial cells to be reprogrammed into neurons by using a small molecule compound and application of the method. The small molecule compound composition is prepared from ISX-9, RO4929097, CHIR99021, VPA, RepSox, Forskolin, SC79 and VC, and growth factors BDNF, GDNF, NT-3 and NGF beta, neuron culture additives B27 and N2 additives are added at the same time, so that survival and maturation of neurons are promoted and induced. Wherein each component is a safe and low-cost small molecule compound and a neurotrophic factor, and the pharmaceutical composition and the growth factor can be used for reprogramming rat dorsal root ganglion satellite glial cells into neurons with specific phenotypes and functional characteristics in vitro. And a new seed cell is provided for basic research of clinical nerve injury diseases and clinical cell treatment development.

The invention belongs to the technical field of organ chips, provides an in-vitro brain lymphatic system chip construction method and a brain lymphatic system chip, and makes up the blank of brain lymphatic system in-vitro model construction. The method comprises the following steps: firstly, carrying out flushing treatment, disinfection and sterilization treatment, rinsing treatment and cell culture on a micro-fluidic channel in the chip; then, in the treated micro-fluidic channel, blood vessel channel cell inoculation and brain parenchyma channel cell inoculation are carried out; and finally, in the blood vessel channel, perfusion is carried out once at a preset flow speed every preset duration, shear force stimulation simulating pulse type blood flow is provided, basic formation of in-vitro cerebral vessels is achieved after continuous perfusion, perfusion is carried out once at a preset flow speed every preset duration, shear force stimulation simulating pulse type blood flow is provided, and in-vitro cerebral vessels are formed. Intermittent liquid flow simulating arterial fluctuation is achieved.