174 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 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 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 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 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 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.

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.

The invention relates to the technical field of biological medicines, and particularly discloses an application composition of stem cell exosomes in promoting tissue repair, which comprises the stem cell exosomes selected from induced pluripotent stem cells, mesenchymal stem cells, embryonic stem cells, hematopoietic stem cells or neural stem cells and used for promoting tissue repair and cell regeneration, and the stem cell exosomes selected from the induced pluripotent stem cells, the mesenchymal stem cells, the embryonic stem cells, the hematopoietic stem cells and the neural stem cells. The tissue repair promoting factor is selected from an epidermal growth factor, a transforming growth factor beta, a platelet-derived growth factor or a combination thereof, and is used for optimizing cell proliferation, differentiation and wound healing; the biodegradable carrier is selected from hydrogel, lipidosome, polymer micelle, nano particles or natural plant extract; by optimizing the transmission relation between the biodegradable carrier and the stem cell exosome and combining with the cell proliferation model, different doses and delivery modes can be flexibly regulated and controlled, the treatment scheme is further optimized, and the effect of the treatment scheme is accurately predicted. Due to the design, the common problems of unstable effect, long treatment period and the like in the traditional stem cell application are solved.

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.