221 results about "Neural stem cell" patented technology

The invention discloses a bionic nanofiber-hydrogel composite biological scaffold as well as a preparation method and application thereof. The bionic nanofiber-hydrogel composite biological scaffold is a composite scaffold for simulating a gray-white matter partition structure of a spinal cord tissue, and comprises bionic nanofibers and a bionic hydrogel material, wherein the bionic nanofibers are arranged in an oriented manner and simulate a white matter ordered structure around the spinal cord, and the bionic hydrogel material is combined with the bionic nanofibers and simulates gray matter in the center of the spinal cord. According to the bionic nanofiber-hydrogel composite biological scaffold, the biological activity of loaded stem cells or adult cells can be improved, the problem that a large number of transplanted exogenous cells die due to unbalanced oxidative stress generated after tissue damage can be solved, and it is guaranteed that the transplanted cells reside in a damaged area and play a role; therefore, the spinal cord microenvironment is improved, proliferation and differentiation of endogenous neural stem cells are promoted, functional recovery after spinal cord injury is finally promoted, and great potential is achieved in spinal cord injury treatment.

The invention provides multifunctional hydrogel, drug-loaded hydrogel as well as a preparation method and application of the multifunctional hydrogel and the drug-loaded hydrogel, and belongs to the technical field of biological medicines. According to the multifunctional hydrogel provided by the invention, the gelatin, the transglutaminase and the sulfhydrylated hyaluronic acid are used as preparation raw materials, so that the problem of limited performance of a hydrogel product in the prior art is solved. According to the hydrogel product prepared by the invention, cell adhesion can be provided through a transglutaminase cross-linked gelatin network, meanwhile, an ROS removal effect is provided through a dynamic disulfide bond cross-linked hyaluronic acid network, and degradation of the hydrogel can be regulated and controlled through combination of the two networks; according to the drug-loaded hydrogel provided by the invention, the exosome derived from neural stem cells is additionally encapsulated in the hydrogel, the exosome and the hydrogel jointly achieve the effects of enhancing inhibition of glial scars and resisting inflammation, and the material provided by the invention can promote repair and regeneration of neurons and myelin sheaths, so that the drug-loaded hydrogel can be used for preparing cerebral hemorrhage treatment drugs and can be used for preparing drugs for treating cerebral hemorrhage. And an effective means is provided for the treatment of related diseases.

The invention discloses an environment-emotion gradient association memristive neural network circuit based on a TAP cell regulation mechanism. The environment-emotion gradient association memristive neural network circuit is composed of a hippocampus module and an amygdala kernel module. The hippocampus module comprises an environment recognition neuron module and an emotion generation neuron module; the environment recognition neuron module and the emotion generation neuron module are each composed of a weight regulation and control module adj based on a TAP cell regulation mechanism, an adder, a memristor, a resistor, an operational amplifier, a function module ABM1 and a sampling holder. Wherein the weight regulation and control module adj is composed of a voltage-controlled switch, a summator, a function module ABM2 and a function module ABM3. The almond kernel module is composed of a weight regulation and control module adj, a memristor, a resistor, an operational amplifier and a sampling holder. The provided circuit simulates the hippocampus and amygdala nucleus of the brain in structure, the regulation principle of TAP cells on neural stem cells is used for reference in a weight regulation mechanism, and bidirectional gradient associated memory of the environment and the emotion can be achieved.

The invention discloses a magnesium-containing nanoparticle modified biological scaffold composite material as well as a preparation method and application thereof. The magnesium-containing nano particle modified biological scaffold composite material comprises a biological scaffold material and magnesium-containing nano particles modified on the biological scaffold material, the magnesium-containing nano particles comprise nano magnesium oxide particles and / or nano magnesium oxide-polyphenol compound particles, the nano magnesium oxide-polyphenol compound particles are of a shell-core structure, and the shell-core structure is of a hollow structure. Comprising magnesium oxide serving as a core and a polyphenol compound shell layer coating the surface of the magnesium oxide. The magnesium-containing nanoparticle-modified biological scaffold composite material provided by the invention can prolong the degradation and release of magnesium ions, promote improvement of microenvironment problems such as inflammation and active oxygen outbreak after spinal cord injury, regulate and control oxidative stress and inflammatory response, promote nerve regeneration and motor function recovery, and improve the survival rate of spinal cord injury. The problem that nanoparticles stop in a spinal cord injury area is effectively solved, and support is provided for migration, growth and differentiation of endogenous neural stem cells.

The invention belongs to the field of medical modification and natural polymer hydrogel, and provides viscosity-adjustable viscoelastic hydrogel and application of the viscosity-adjustable viscoelastic hydrogel in evaluation of influence of hydrogel viscosity on cell behaviors. Through a double crosslinking mechanism of covalent crosslinking and ionic crosslinking, two viscoelastic hydrogels with the same initial modulus and different viscosities are prepared. The covalent cross-linked hydrogel is composed of methylacryloylated alginic acid (AlgMA), gelatin (Gel) and phenyl (2, 4, 6-trimethylbenzoyl) lithium phosphate (LAP), and the ionic cross-linked hydrogel is composed of sodium alginate (Alg), gelatin (Gel) and calcium chloride. By accurately controlling the crosslinking degree, fine adjustment of the viscosity of the hydrogel is realized without changing the initial modulus of the hydrogel, which has important influence on adhesion and survival of neural stem cells. The experimental method provided by the invention verifies the key effect of the viscosity of the viscoelastic matrix in cell behavior regulation.

The invention discloses a protein marker for detecting or evaluating human neural stem cell paracrine and application thereof, the protein marker is a combination of SERPINE2, NCAN, VCAN, PTN, NRP2, PTPRF, C1QL1 and LDLR.The screening method comprises the steps that total protein in a human neural stem cell sample is extracted for proteome analysis and reference genome transcriptome analysis; and carrying out data processing and comparison screening to obtain common protein with high protein abundance expression and a forward regulation function, and carrying out ELISA (enzyme-linked immunosorbent assay). The human neural stem cell paracrine is detected or evaluated by detecting the expression level of the protein marker, and the application value is high.

The invention relates to the field of cell biology, and particularly discloses a neural stem cell induced differentiation culture medium and application thereof in preparation of neural stem cells. The neural stem cell induced differentiation culture medium is composed of a basic culture medium and additives, wherein the additives are composed of an N-2 additive, a B-27 additive, glutamine, a human leukemia inhibiting factor, a GSK-3 inhibitor, an ALK inhibitor, a gamma-secretase inhibitor and a CDK8 inhibitor. The neural stem cell induced differentiation culture medium is clear and simple in component, does not need to use antibiotics, and does not contain animal-derived components. When the culture medium is used for carrying out differentiation induction on the human pluripotent stem cells, the human pluripotent stem cells can be induced and differentiated into the neural stem cells within a short time (6-7 days) without depending on pluripotent stem cell cloning and a single cell state, the nonuniformity of pluripotent stem cell cloning formation can be overcome, and the purity of the neural stem cells is improved.

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 relates to a microneedle for exosome injection, and relates to the field of medical instruments, the microneedle comprises a syringe, a pressure lever and a needle body, the syringe is filled with exosome secreted from neural stem cells, one end of the pressure lever is slidably connected in the syringe, and the other end of the pressure lever extends out of the syringe; the needle body is connected with the syringe, the sharp part of the needle body is punctured into the acupuncture point, the pressing rod moves towards the needle body to inject the exosome into the acupuncture point from the inside of the needle body or the outside of the needle body, and the acupuncture needle has the advantages that acupuncture and exosome injection are combined, and the acupuncture needle can play roles in easing pain, promoting tissue regeneration and repair, regulating the immune function and improving neurological function coordination and synergy.

The invention discloses a method for efficiently and rapidly differentiating microglial cells. According to the invention, the iPSC is creatively differentiated into the neural stem cells, and then the neural stem cells are induced and differentiated to obtain the microglial cells. The microglial cells obtained by applying the scheme show excellent homogeneity and relatively high yield; the differentiation scheme is simple and convenient, and microglial cells with relatively high purity can be obtained without suspension culture or a low-oxygen environment; meanwhile, the method disclosed by the invention is short in time consumption, the microglial cells with relatively high purity can be obtained only in 14 days, and the differentiation time is greatly shortened.

The invention relates to the technical field of cell biology, in particular to a culture medium for inducing neural stem cells and application thereof.The culture medium for inducing the neural stem cells comprises a neural ectoderm induction culture medium and a neural stem cell induction culture medium; the neural ectoderm induction culture medium is prepared from a basic culture medium, an N-2 additive, a B-27 additive, an inhibitor SB431542 and an inhibitor Dorsomorphin, the neural stem cell induction culture medium is prepared from a basic culture medium, an N-2 additive and a B-27 additive, the basic culture medium is composed of a DMEM / F12 culture medium, a Neurobase culture medium, GlutaMax and non-essential amino acid NEAA. The problems that neural stem cells obtained through an existing single-layer adherent induction method based on small molecules or growth factors are uneven in differentiation and low in purity are solved.

The present disclosure describes formulations, methods, and devices for biomarker sampling and therapeutic delivery using magnetic formulations. When combined with the application of external magnetic fields, magnetic formulations move within the nasal cavity. Magnetic formulations provide benefits including the ability to: target or steer placement of the formulations via a magnetic field, enhance mixing of the formulation via a magnetic field, enhance biological material collection via antibody-coated magnetic beads, or enhance sample retrieval via a magnetic-tipped inserter. Example biological materials for collection include proteins, enzymes, neural stem cells, and other biomarkers.

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 material preparation, and particularly relates to a preparation method of a self-oxygen-supply hydrogel cell scaffold, an obtained product and application. According to the invention, stable and continuous release of oxygen and three-dimensional (3D) culture of neural stem cell spheres are realized. The method is realized by the following steps: adding compounds P-MA, P-Cys, ColMA and PEG-CaO2 into a PBS (Phosphate Buffer Solution), adding a photoinitiator, and irradiating and curing by ultraviolet light with the wavelength of 365nm to obtain the self-oxygen-supply composite hydrogel. The invention provides a novel method for applying composite hydrogel loaded with oxygen-producing nano-particles to 3D cell sphere culture and continuously releasing O2 in a slightly acidic environment to solve the problems of death of intermediate cells caused by oxygen deficit in the 3D culture process of existing cell spheres, indefinite components of matrigel, high price and the like. The problem of internal oxygen deficit in the cell ball culture process is solved, and the gel component is defined to be used for researching the effect between other components and cells. In addition, the self-oxygen-supply hydrogel material prepared by the technology is expected to be applied to 3D culture of other cell spheres or organoid spheres.

The present invention relates to a pharmaceutical composition for preventing and treating senile diseases, which contains neural stem cells derived from hypothalamic organs as an active ingredient. When the neural stem cell derived from the hypothalamic organ according to the present invention is transplanted into the body of an aged mouse, the memory, cognitive ability, muscle strength, muscle tissue density, and bone mineral density of the aged mouse are restored due to aging. In addition, transplantation of hypothalamic organ-derived neural stem cells has also been found to ameliorate obesity by increasing energy metabolism. It is found that when the exosome separated from the neural stem cells derived from the hypothalamic-like organ is transplanted into the body of an aged mouse, the reduced memory, cognitive ability and muscle strength of the aged mouse are also recovered. Therefore, the neural stem cell derived from the hypothalamic organ according to the present invention is expected to be a very useful agent for preventing and treating senile diseases.

The invention relates to a genetically modified induced neural stem cell and an asynchronous co-culture method. By providing a CRISPR / Cas9 engineered Nurr1-driven dopamine energy report induced neural stem cell model, the differentiation of dopaminergic neural precursor cells and neurons can be monitored in real time, a key pathway related to differentiation heterogeneity is revealed through RNA sequencing, an asynchronous co-culture method is established, and the method has the advantages of simple operation, low cost and high efficiency. The yield and purity of the dopaminergic nerve precursor cells can be improved, and the dopaminergic nerve precursor cells are successfully transplanted and differentiated into dopaminergic neurons in mouse striatum to prove the treatment potential of the dopaminergic nerve precursor cells for Parkinson's disease.

The present invention provides a compound with which a molecular probe capable of distinguishing NSCs from CSCs can be produced, and a method for detecting cancer stem cells using the compound. The present invention relates to a compound having a formyl group, a substrate moiety, a quenching moiety, and a luminescent moiety that is non-luminous due to the quenching moiety, wherein the luminescent moiety may be rendered luminous by detaching the substrate moiety by a substrate-degrading enzyme and also converting the formyl group to a carboxy group by an aldehyde dehydrogenase to allow the quenching moiety to dissociate.

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.

The invention discloses a method for promoting differentiation of primary neural stem cells based on ultrasonic patterning. Putting the cell slide into a cell culture dish, adding a poly-D-lysine solution to immerse the cell slide, preserving in a dark place at room temperature, completely absorbing the solution, cleaning the slide, and airing for later use; placing the cell culture dish in a sound field generator in an ultrasonic device, and adding sterile water into a gap area; emitting ultrasonic waves by using an ultrasonic device, and adding the cell suspension containing the primary neural stem cells into a cell culture dish; and stopping emitting the ultrasonic waves, transferring the cell culture dish into an incubator for culturing, and then replacing the culture medium for culturing to obtain mature nerve cells. According to the method, the one-dimensional ultrasonic standing wave field is applied in the early stage of the cell culture process to remarkably promote the differentiation rate of in-vitro culture of the neural stem cells, the spatial arrangement of the primary neural stem cells is accurately controlled by adopting a non-contact method, ultrasonic field patterning is realized, damage to the cells is reduced, and operation safety and cell activity are ensured.

The invention provides a cleaning and preserving fluid for fetal brain tissues and a preserving method thereof, and belongs to the technical field of tissue preservation. The cleaning and preserving fluid comprises trehalose, nerve growth factors, a GlutaMAX supplement, Y27632, S-nitrosoglutathione, tert-butylhydroquinone, a Versene solution and polyvinylpyrrolidone, compared with a traditional tissue preserving fluid, the cleaning and preserving fluid not only can improve the purity of neural stem cells, but also can maintain the activity and the yield of the neural stem cells in fetal brain tissue, and the cleaning and preserving fluid has the advantages that the cleaning and preserving fluid is simple in structure and convenient to use. The structural integrity of the cells is guaranteed, a high-quality sample is provided for subsequent research on proliferation, differentiation and the like of the neural stem cells, and the method has a wide application prospect.

The present invention relates to a method for generating an enriched population of early cortical neural stem cells (NSCs) or a subpopulation thereof, the method comprising: isolating cells that are positive for the cell surface marker protogenin (PRTG) from an initial population of neural progenitor cells, wherein said isolating is conducted at a time point between about day 4 and about day 12, preferably on day 5, after initiation of neural induction, thereby obtaining an enriched population of early cortical neural stem cells (NSCs); and optionally re- culturing said enriched population of early cortical neural stem cells (NSCs) in a neural induction medium or other culture medium, wherein said re-culturing preferably produces progeny of said early cortical neural stem cells (NSCs).

The present invention discloses a stem cell preparation sponge patch complex and a preparation method thereof. The sponge patch complex is a degradable sponge body infiltrated with a stem cell suspension, and the degradable sponge body is made of gelatin, modified sodium alginate, and polyethylene glycol-polylysine-polyvaline triblock copolymer; the mass ratio of the gelatin, modified sodium alginate, and polyethylene glycol-polylysine-polyvaline triblock copolymer is 5:(1-6):(1-6). In the present invention, a degradable sponge body is prepared with modified sodium alginate and polyethylene glycol-polylysine-polyvaline triblock copolymer, which can accommodate more stem cells, improve the stem cell loading capacity, and L-carnitine and vitamin E are added to the complete medium for neural stem cells, thereby improving the survival rate of stem cells.

The present application concerns methods for detecting and isolating a population of neural stem cells (NSC) or neural progenitor cells (NPC) based on expression of the marker integrin alpha10beta1; as well as use of said population of NSC or NPC for therapy, diagnosis and prognosis of disease and damage of the CNS.

The invention provides a traditional Chinese medicine compound composition with a nerve repairing effect, a cell culture medium, a traditional Chinese medicine-neural stem cell exosome compound and application, and belongs to the technical field of biological medicine. Based on the basic theory of traditional Chinese medicine and the combined theory of traditional Chinese medicine and western medicine, the traditional Chinese medicine compound composition is provided and comprises gastrodia elata exosomes, astragalus membranaceus exosomes and resveratrol, the traditional Chinese medicine compound composition is prepared into a cell culture medium, neural stem cells are cultured through the cell culture medium, and the neural stem cells are obtained. Therefore, the traditional Chinese medicine-neural stem cell exosome compound with an efficient nerve repairing function is prepared. The traditional Chinese medicine-neural stem cell exosome compound achieves the purpose of comprehensively repairing nerve injury by precisely targeting nerve cells, promoting neurogenesis, repairing the function of a neural circuit and reducing the inflammatory effect, and can be used for preparing related medical instruments and drugs for nerve repair.

A method for generating human midbrain immature neurons and mature dopaminergic neurons from neural progenitor cells is provided. The immature and mature midbrain neurons are obtained from neural progenitor cells such as committed midbrain neural stem cells (NSCs) and midbrain neural progenitor cells (midbrain NPCs), which are themselves generated from human pluripotent stem cells. The method for generating midbrain immature neurons and mature neurons uses a chemically defined medium that enables the generation of mature dopaminergic neurons in just 23 days. Media, isolated cell populations, and kits are also provided.

The invention relates to the field of biological medicine, and provides a neuronal cell differentiation culture medium which comprises a basic culture medium, a ROCK pathway inhibitor, a cAMP level enhancer, a neural stem cell differentiation inducer and gamma-aminobutyric acid. The neuronal induced differentiation culture medium provided by the invention is clear in component and convenient to use, and can quickly differentiate the human pluripotent stem cells into neurons with relatively mature shapes and functions. By applying the technical scheme disclosed by the invention, the problems of overlong in-vitro neuronal differentiation period, low purity of obtained neurons, immature functions and the like can be solved, and the method has very high scientific research and clinical application prospects.

The present application provides methods for generating human midbrain immature neurons and mature dopaminergic neurons from neural progenitor cells. In some embodiments, immature and mature midbrain neurons are obtained from neural progenitor cells, such as targeted midbrain neural stem cells (NSCs) and midbrain neural progenitor cells (midbrain NPCs), while they themselves are generated from human pluripotent stem cells. Methods for generating immature and mature neurons of the midbrain use a chemically defined medium that allows for the generation of mature dopaminergic neurons within a short of 23 days. Media, isolated cell populations, and kits are also provided.

An extracellular vesicle based therapeutic compound for treating tumors and cancers. The extracellular vesicle based therapeutics use exosomes that are transdifferentiation-derived induced neural stem cells (Exo-iNSCs) that produce an extracellular vesicle having a tumoricidal gene product or an anti-cancer molecule withing the extracellular vesicle. The therapeutic agent is present in a lumen of the extracellular vesicle or is distributed across a membrane surface of the extracellular vesicle. Methods of using the extracellular vesicle based therapeutic compounds are effective in treating tumors and cancers.

The low-oxygen pretreatment method comprises the following steps: inoculating neural stem cells into a neural stem cell culture medium, and continuously culturing for 7 days under the conditions that the oxygen concentration is 5%, the temperature is 37 DEG C, the humidity is 95% and the CO2 content is 5%. The neural stem cells cultured by the method disclosed by the invention highly express NRG1, ALK and SEPTIN7 genes, have higher survival rate and proliferation level in vivo, and have a better treatment effect on cerebral arterial thrombosis. According to the hypoxia pretreatment method, the potential curative effect of neural stem cell transplantation for treating nervous system diseases can be improved, a breakthrough result is obtained through deep analysis of oxygen concentration and metabolism adaptation interaction, and the hypoxia pretreatment method has great application potential.

The present invention relates to a composition for preventing, alleviating, or treating neuronal aging-related diseases or disorders, the composition comprising extracellular vesicles derived from three-dimensional spheroid-type cell aggregates. The extracellular vesicles according to the present invention can reduce the expression of aging-related proteins and induce reactivation of aged neural stem cells, and thus can be used to treat various neuronal aging-related diseases or disorders by preventing, alleviating, or treating the aging of neurons.