132 results about "Neural stem cell" patented technology

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 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 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 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 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 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 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.

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 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.

The application discloses a method for differentiating stem cells into caudal serotonergic neurons, a complete culture medium and application. Specifically, a new culture medium is formed by adding small molecule compounds, so that human pluripotent stem cells are gradually induced to obtain hindbrain neural stem cells, ventral hindbrain caudal neural stem cells, serotonergic precursor cells and caudal serotonergic neurons of the hindbrain. The culture method is simple, and can efficiently obtain mature serotonergic neurons of specific regions, thereby providing an effective cell model for research on diseases related to the serotonergic system.

This invention provides a pH-responsive immunomodulatory microneedle patch, its preparation method, and its application, belonging to the field of biomedical materials technology. This invention incorporates Zif-8 nanoparticles loaded with ChABC into GelMA hydrogel to prepare a pH-responsive immunomodulatory microneedle patch (Z@C-MN). As the patch gradually degrades, the system can continuously release Zn in a pH-responsive manner. 2+ Z@C-MN, along with ChABC, promotes in situ repair of cerebral fibrosis (SCI) after injury. Z@C-MN induces macrophage polarization towards a pro-regenerative phenotype, thereby downregulating the inflammatory response, increasing neurite length, and promoting the differentiation of neural stem cells into neurons. In vivo, Z@C-MN reduced the inflammatory microenvironment after injury and promoted angiogenesis in a rat SCI model. Furthermore, it activated axonal regeneration by inhibiting scar tissue formation and regulating CD4+. + T cell transformation supports neurogenesis.

The invention discloses a multi-layer composite artificial cochlea electrode coating material with multiple anti-inflammatory and electrode-neuron repairing functions and a preparation method of the multi-layer composite artificial cochlea electrode coating material. The preparation method specifically comprises the following steps: constructing a silver elementary substance coating on an artificial cochlea electrode platinum-iridium alloy contact base material by using a physical vapor deposition process; an electrode contact is obtained by combining a vacuum ultrashort pulse laser processing technology, and a methacrylated silk fibroin SilMA microsphere material loaded with bilirubin is prepared by a microfluidic technology; preparing gold-copper clustering enzyme by using a wet chemical reduction method; the preparation method comprises the following steps: preparing a porous methacrylated gelatin solution, composite neural stem cells, SilMA drug-loaded microspheres and gold-copper clustered enzyme; after in-situ curing and demolding are carried out on the surface of the artificial cochlea electrode by combining a mold pouring method, a multi-layer composite artificial cochlea electrode coating material with multiple anti-inflammatory and electrode-neuron repairing functions is obtained on the surface of the electrode, and the coating can provide a cell source for nerve deafness repairing and complete electrode-neuron repairing; and multiple anti-inflammatory functions are realized.

The invention discloses a culture medium for promoting neural stem cell proliferation by using a small molecule compound and a preparation method, and belongs to the technical field of medicines. Comprising a basic culture medium and a small-molecule compound, the basic culture medium comprises the following components in parts by weight: 60-100 parts of agar, 20-40 parts of peptone, 8-12 parts of glucose, 1-3 parts of sodium chloride and 0.1-0.5 part of vitamin; the concentration of the small molecule compound in the culture medium is 20-100 [mu] M, and the small molecule compound comprises at least one of isoacteoside, vitamin P4, salvianolic acid B and 1, 2, 3, 4, 6-O-galloylglucose. The small molecule compound used in the invention activates a downstream gene expression regulatory network through specific targeting of TLX, effectively reverses decline of proliferation ability of neural stem cells, and provides a new method for in vitro amplification of high-quality neural stem cells. Meanwhile, the small molecule compounds also have a synergistic effect, and proliferation of the neural stem cells is promoted.

The invention relates to a lipid nutritional composition, a product comprising the same and application of the lipid nutritional composition in preparation of a product for promoting structural development of neural stem cells. The lipid nutritional composition comprises: docosahexaenoic acid and / or a metabolic precursor thereof; arachidonic acid and / or a metabolic precursor thereof; and a population of phospholipids consisting of phosphatidylcholine (PC) and / or a metabolic precursor thereof, phosphatidylserine (PS) and / or a metabolic precursor thereof, phosphatidylethanolamine (PE) and / or a metabolic precursor thereof, phosphatidylinositol (PI) and / or a metabolic precursor thereof, and sphingomyelin (SM) and / or a metabolic precursor thereof; wherein the ratio of the molar equivalents of arachidonic acid to the molar equivalents of docosahexaenoic acid, ARA / DHA, is 1-2: 1; and the ratio of the total molar equivalents of the phospholipid population to the molar equivalents of docosahexaenoic acid, PHL / DHA, is 1-8: 1.

The invention discloses a pharmaceutical composition for preventing and / or treating Parkinson's disease and application of the pharmaceutical composition, and relates to the technical field of biological medicine. The composition comprises nervonic acid, salvianolic acid A and pharmaceutically acceptable auxiliary materials. Experiments prove that the composition can improve intestinal flora, obviously promote alleviation of symptoms of a Parkinson's disease model animal, promote regeneration of dopaminergic neuronal cells and neural stem cells, relieve neuroinflammation, promote repair of damaged nerves, improve dyskinesia of mice caused by Parkinson's disease and improve the Parkinson's disease resistance of the mice. Therefore, the polypeptide has potential application value in treatment of the human Parkinson's disease. According to the invention, the effect of the composition is confirmed from the perspective of improving the change of intestinal flora by utilizing the relationship of the brain-intestinal axis, and a basis is provided for intervening the treatment of Parkinson's disease through the intestinal flora.

The invention discloses an enzyme response magnetic resonance imaging nanoprobe as well as a preparation method and application thereof. The enzyme response magnetic resonance imaging nanoprobe comprises a metal nanoparticle with a surface functional group A as an imaging basic unit, and a polypeptide sequence with functional groups B at two ends as a cross-linking agent and an enzyme response unit, the enzyme response magnetic resonance imaging nano-probe is a metal nano-particle cross-linked body formed by cross-linking the metal nano-particles through a polypeptide sequence. The enzyme response magnetic resonance imaging nanoprobe disclosed by the invention can be specifically cut by a high-expression enzyme in a cell differentiation process to form monodispersed metal nanoparticles, so that signal transformation is presented on magnetic resonance imaging; meanwhile, the enzyme response magnetic resonance imaging nanoprobe can establish effective association among the probe existence form, the cell state and the imaging signal, and is used for tracking the directional differentiation process of mesenchymal stem cells, neural stem cells and promyelocytic leukemia cells in real time.

The invention relates to the technical field of biological medicines, and discloses an engineered exosome preparation containing a myeloid tonifying pill extract, which is prepared from the following raw materials in parts by weight: 20 to 50 parts of exosome source cells, 5 to 90 parts of myeloid tonifying pill extract, 0.05 to 0.5 part of targeting molecules, 2 to 5 parts of trehalose, 0.5 to 2.5 parts of polyethylene glycol, 0.2 to 1 part of cholesterol and 1 to 4 parts of hyaluronic acid. The exosome source cells are one or more of neural stem cells and mesenchymal stem cells. The preparation process of the engineered exosome preparation containing the marrow supplementing pellet extract is subjected to clear and ordered step limitation, and then the whole preparation process is standardized, so that the problems that most traditional preparation processes of the preparations are not rigorous enough and have fuzzy steps, clear operation guidance is lacked, and the preparation cost is low are solved. Therefore, the medicine effect of the preparation is unstable.

The present invention discloses a bioactive scaffold for slowly releasing Apt19S to recruit endogenous stem cells and guide the straight regeneration of central nervous system axons and its application. The bioactive scaffold is composed of acellular optic nerve (DON) and aptamer Apt19S, and its preparation method comprises the following steps: 1. preparing a DON scaffold. 2. activating the carboxyl group on the surface of the DON scaffold. 3. The DON scaffold is combined with amino-modified Apt19S through an amidation reaction to obtain the DON‑Apt19S scaffold (abbreviated as DON‑A). This bioactive scaffold can continuously release Apt19S, recruit ALPL-positive endogenous neural stem cells and mesenchymal cells, guide the straight regeneration of central nervous system axons, and provide a microenvironment for neurogenesis and angiogenesis for in situ spinal cord repair. The bioactive scaffold has important transformation prospects and application value in the repair of central nervous system injuries.

The invention provides multifunctional hydrogel carrying neural stem cells. The multifunctional hydrogel mainly comprises the following components: chitosan, beta-sodium glycerophosphate, edaravone, nerve growth factors and the neural stem cells, the invention also provides a method for preparing the multifunctional hydrogel, which comprises the following steps: preparing temperature-sensitive hydrogel by taking a chitosan solution and a beta-sodium glycerophosphate solution as matrixes, preparing an edaravone-nerve growth factor mixed solution, and preparing the edaravone-nerve growth factor composite hydrogel. Sequentially adding a neural stem cell suspension and the mixed solution into a hydrogel system to obtain the multifunctional hydrogel carrying the neural stem cells. The multifunctional hydrogel disclosed by the invention realizes high-efficiency integration of three core functions of temperature-sensitive positioning, drug sustained-release microenvironment regulation and control and cell proliferation and differentiation support, and can remarkably promote spinal cord injury repair.

The application discloses an enzyme-responsive magnetic resonance imaging nano probe and a preparation method and application thereof. The enzyme-responsive magnetic resonance imaging nano probe comprises a surface functional group A metal nanoparticle as an imaging basic unit, and a functional group B polypeptide sequence as a crosslinking agent and an enzyme-responsive unit; and the enzyme-responsive magnetic resonance imaging nano probe is a metal nanoparticle crosslinking body formed by crosslinking the metal nanoparticle through the polypeptide sequence. The enzyme-responsive magnetic resonance imaging nano probe can be specifically cut by an enzyme highly expressed in a cell differentiation process, and forms a monodispersed metal nanoparticle, so that a signal change is presented on magnetic resonance imaging. Meanwhile, the enzyme-responsive magnetic resonance imaging nano probe can establish an effective correlation among a probe existing form, a cell state and an imaging signal, and is used for real-time tracking of a directional differentiation process of mesenchymal stem cells, neural stem cells and promyelocytic leukemia cells.

The application discloses an application of miR-345-3p inhibitor in preparation of a product for promoting differentiation of neural stem cells in vitro, and belongs to the technical field of biological medicine. The application obtains miRNAs differentially expressed in a neuron differentiation process through GEO2R analysis, and miR-345-3p is one of the miRNAs significantly underexpressed; then the expression of miR-345-3p is down-regulated by using a miRNA inhibitor, and the result shows that the miR-345-3p inhibitor can promote differentiation of neural stem cells into neurons in vitro P <0.05), and underexpression of miR-345-3p can obviously promote differentiation of neural stem cells into neurons P <0.05). Therefore, a substance for promoting underexpression of miR-345-3p can be applied to preparation of a product for promoting differentiation of neural stem cells into neurons in vitro.

The application discloses an induction method for directional differentiation of neural stem cells into dopaminergic neurons, comprising the following steps: S1, activation and adhesion of NSCs; S2, directional induction of midbrain precursor cells; S3, directional induction of dopaminergic neurons; and S4, synaptic function maturation induction. The induction method for directional differentiation of neural stem cells into dopaminergic neurons can significantly improve the directional efficiency and lineage specificity of the midbrain precursor cells: by adding salvianolic acid B and icariin, and in cooperation with SHH, FGF8 and other induction factors, the midbrain lineage-specific signal pathway can be efficiently activated, the positive rate of the midbrain precursor cell marker LMX1A is increased to more than 76%, which is far better than 49% of the existing system, and abnormal differentiation of non-midbrain lineages is effectively inhibited.

Disclosed are compositions including a population of human enteric neural stem cells (ENSCs), wherein the population comprises at least one of a cell expressing nerve growth factor receptor (NGFR), a cell expressing integrin alpha 6 (ITGA6), a cell expressing L1 cell adhesion molecule (L1CAM), a cell that expresses proteolipid protein 1 (PLP1), and / or a cell that expresses paired-like homeobox 2B (PHOX2B), methods of producing the compositions, and their uses.

The present invention relates to a method of converting human fibroblasts into neural stem cells, and more particularly, to a conversion method through direct cross-differentiation of human fibroblasts into neural stem cells using a combination of Sendai virus, mRNA or miRNA of a stem cell-related factor, and a small molecule compound, and a use thereof. According to the present invention, since high-quality neural stem cells may be induced from human fibroblasts through direct cross-differentiation within a short period of time, it is possible to secure a sufficient amount of cells for cell therapy, and since there is no side effect of tumorigenesis, the present invention may be used as a cell therapeutic agent for brain diseases.

The present invention discloses a scaffold-gel composite central nervous system repair material for specifically attracting and incubating endogenous neural stem cells and its application. The composite central nervous system repair material is composed of a decellularized optic nerve scaffold, a decellularized spinal cord hydrogel, neurotrophic factors, and the aptamer Apt19S. The above-mentioned scaffold can continuously release Apt19S and neurotrophic factors, recruit a large number of endogenous stem cells, and provide a neurogenesis microenvironment and physical support performance support for in situ spinal cord repair. The composite central nervous system repair material can be transplanted into the spinal cord injury site to repair spinal cord injury, and can also be transplanted into the optic nerve or brain injury site to repair central nervous system injury.

The invention relates to a neural stem cell exosome miR-106b compound and application of the neural stem cell exosome miR-106b compound in treatment of neurodegenerative diseases. It is found for the first time that the miR-106b-carrying neural stem cell exosome compound can effectively reduce damage to neurons and synapses and relieve neuroinflammation in in-vitro and in-vivo experiments. Animal experiment results show that in-vivo injection of the compound or the miR-106b simulant can be used as a treatment means for inhibiting neuroinflammation, and cognitive function decline related to neurodegenerative diseases can be resisted.

The invention discloses application of Nrsn1 in preparation of a medicine for differentiating neural stem cells into neuronal cells, and belongs to the technical field of neurobiology. The invention provides application of Nrsn1 in preparation of a medicine for differentiating neural stem cells into neuronal cells. The invention relates to application of Nrsn1 in preparation of drugs for preventing and / or treating cerebral arterial thrombosis or neurodegenerative diseases. It is found that the Nrsn1 gene can promote the neural stem cells to be differentiated into neurons, and the efficiency of differentiating the neural stem cells into the neurons is improved.