1027results about "Nervous system cells" patented technology

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.

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.

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.

Provided herein are peptide amphiphiles (PAs) comprising a bioactive peptide, nanofibers displaying the bioactive PAs, and methods of use thereof. The disclosed peptide amphiphiles comprise a hydrophobic tail, a structural peptide segment, a charged peptide segment, and a bioactive IKVAV peptide. The disclosed PAs may be used in cell culture methods and in methods of treating central nervous system injury.

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.

Some embodiments relate to improved cryopreservative formulations and improved methods for cryopreserving and thawing cells. These formulations facilitate high density, low volume cell cryopreservation strategies which overcome the need for washing of cells post-thaw, and therefore result in greater cell recovery and viability. Pharmaceutical compositions comprising a cell population and a cryopreservative formulation as provided herein are also provided. Methods for treating a subject having a disease or condition that benefits from transplantation of a cryopreserved and thawed cell population are also provided.

To provide antisense oligonucleotide sequences and methods of using the same for treating neurological diseases.SOLUTION: Provided is an oligonucleotide comprising linked nucleosides having a sequence of at least 19 contiguous nucleobases, wherein the sequence of nucleobases comprises a portion of at least 10 contiguous nucleobases that is at least 90% complementary to an equal length portion of nucleobases contained at a specified position of a specified sequence.SELECTED DRAWING: Figure 1A

This invention relates to the technical field of stem cell induction differentiation and transplantation therapy, specifically to a method for inducing human induced pluripotent stem cells to differentiate into dopaminergic neuronal progenitor cells, comprising the following steps: S1, human induced pluripotent stem cells are induced to differentiate into primitive neuroepithelial cells under the action of SB431542, DMH1, SHH, FGF8b, Purmorphamine, and CHIR99021; S3, intermediate primitive neuroepithelial cells are continuously induced to differentiate using BDNF, GDNF, AA, N2, B27 (without added vitamin A), cAMP, and GlutaMax to obtain dopaminergic neuronal progenitor cells. The dopaminergic neuronal progenitor cells obtained using the method provided by this invention can survive for a long time in the brain microenvironment of Parkinson's rats and have a significant repair effect on rat motor dysfunction.

The application discloses a method for preparing cell-derived exosomes and products and applications thereof, and the method comprises the following steps: co-culturing immune-activated programmable cells with a stimulating agent with immune-activation effect, and collecting the cell-derived exosomes with immune activity by a natural secretion collection method or an artificial extrusion collection method. The application has safe and controllable local immune activation, and the immune activation strategy based on the exosomes fully overcomes the safety bottleneck of traditional live bacterial preparations in tumor treatment. By replacing live bacteria with engineered exosomes, not only potential risks such as systemic inflammatory response and infection are effectively avoided, but also the local controllability of immune stimulation signals is ensured, the precise activation and directional regulation of tumor region immune cells are realized, the tumor microenvironment is reshaped, the anti-tumor effect is strengthened, and the broad-spectrum cross-tumor potential is verified across models.

As botulinum toxin has recently been attempted as a therapeutic agent for various indications, the demand for botulinum toxin in the medical and cosmetic fields has rapidly increased. However, there is no stable and highly reproducible cell-based assay method for measuring the potency of botulinum toxin. Since botulinum toxin is a very potent neurotoxin protein, the development of highly specific and sensitive cells is particularly required for accurate cell-based measurement of the potency of botulinum toxin. The present invention is directed to a neuronal cell line with altered gene expression. The transformed cell line according to the present invention has significantly increased sensitivity to botulinum toxin, and thus is expected to be very effectively used for cell-based determination of botulinum toxin activity or cell-based detection of botulinum toxin.

To provide a method for generating oligocortical spheroids (OCS) from pluripotent stem cells (PSC).SOLUTION: A method comprises the steps for: a) generating a neurocortical spheroid (NCS) through neurocortical patterning of pluripotent stem cells; b) subjecting the neurocortical spheroid to timed exposure to defined oligodendrocyte lineage growth factors and / or hormones, to promote proliferation, survival and / or expansion of native oligodendrocyte progenitor cell (OPC) populations within the neurocortical spheroid, thereby generating the oligocortical spheroid, wherein the oligocortical spheroid contains oligodendrocyte progenitor cells capable of differentiating into myelinating oligodendrocytes (ODCs) that are capable of myelinating axons.SELECTED DRAWING: Figure 1-1

Provided herein are completely defined two-dimensional culture conditions, including culture supplements and requirements for an extracellular matrix, facilitating the expansion of and long-term maintenance of primary human hepatocytes, as well as culture conditions and media for maturation of hepatocytes.

Methods for generating mature somatostatin+ interneurons from human forebrain neural progenitor cells are provided using chemically-defined culture media in a two-stage culture protocol. The mature somatostatin+ interneurons are generated from medial ganglionic eminence neural progenitor cells (MGE-NPCs), which themselves are differentiated from pluripotent stem cells. Culture media, isolated cell populations and kits are also provided.

This invention relates to the field of organoid disease models, and discloses a method for constructing a human brain organoid model of early-onset Alzheimer's disease (AD) and its applications. This invention introduces [a specific technology] into human embryonic stem cell lines through single-base editing and lead editing techniques. PSEN1 ΔE9、 PSEN1 M146V and APP Human embryonic stem cell lines carrying four familial pathogenic gene mutations (K670N and M671L) were constructed and induced to differentiate into Alzheimer's disease (AD) brain organoids. The AD brain organoid model established by this invention exhibited tau phosphorylation pathological phenotypes as early as 20 days and Aβ-related phenotypes as early as 40 days, with increased total Aβ, decreased Aβ42 / Aβ40 ratio, and simultaneous aggravation of Aβ-Tau pathology. This represents a complex neurodegenerative pathological model where multiple mutations synergistically regulate Aβ production and tau phosphorylation, which is highly valuable for understanding and studying early-onset familial AD. This invention provides a human brain organoid model for in vitro AD studies and offers a tool for studying the pathological mechanisms of AD and screening drugs.

The present disclosure provides methods of producing midbrain dopaminergic neurons (mDAs) and precursors thereof, mDAs and precursors thereof produced thereby, as well as compositions comprising these cells, and their use for the prevention and / or treatment of neurological diseases. The present disclosure also provides methods of isolating mDA and precursors thereof from cell populations using novel surface markers.

The present disclosure relates generally to methods and systems of producing Schwann cells from pluripotent stem cells under fully defined conditions. The Schwann cells produced by the disclosed methods find applications as models of the enteric nervous system, tools for high throughput screening of potential therapeutics for treatment of enteric neuropathies, and in regenerative medicine.

Provided is a detection technique excellent in cell drying resistance, cell retention, and detection of a chemical substance such as an odorant. More specifically, provided are: a laminate containing

The present invention addresses the problem of providing a method for producing a suprachiasmatic nucleus cell organoid. The problem is solved by a method for producing a suprachiasmatic nucleus organoid comprising: (1) a step for culturing pluripotent stem cells in an intermediate medium between an undifferentiation maintenance medium and a nerve differentiation medium; (2) a step for culturing the cells obtained in step (1) in a nerve differentiation medium; and (3) a step for performing an operation for forming a cell mass prior to the start of step (2), wherein (A) the number of raw material cells seeded in order to form one cell mass is 6000 or more, and (B) when the start of step (2) is taken as day 0, the medium contains a sonic hedgehog signaling pathway agonist from day 3 onward.

The application provides a toxicity-enhanced neurotoxin recombinant protein and application thereof, and belongs to the technical field of biological medicine. The recombinant protein comprises a botulinum toxin type A receptor binding domain and at least one GM1 binding peptide inserted into the botulinum toxin type A receptor binding domain, and the recombinin protein can recognize and bind to ganglioside GM1. The short peptide sequence capable of binding to ganglioside GM1 is introduced into the botulinum toxin type A receptor binding domain to obtain the recombinant protein, the binding capacity of the recombinant protein to ganglioside GM1 is enhanced, the target recognition and binding capacity of the recombinant protein to the nerve cell membrane are improved, the overall affinity and endocytosis efficiency of the recombinant protein to the nerve cell are improved, and the neurotoxicity of the botulinum toxin is enhanced. The application not only improves the binding efficiency of BoNT / A in the in-vitro nerve cell model, but also shows a higher toxicity level in the functional verification, and shows a good clinical conversion prospect.

The purpose of the present invention is to provide a novel method for culturing tissue-derived cells. The method uses a cell culture method including a step for co-culturing cells derived from the skin and at least one type of cell selected from among cells derived from the intestine, cells derived from the heart, cells derived from the brain, cells derived from the stomach, cells derived from the embryonic membrane, cells derived from the kidney, and cells derived from the lung. And culturing the skin-derived cells.

This application relates to methods of cryopreserving cells for modeling a human brain, a human blood-brain barrier, or a human microvasculature. Also provided are assays based on an induced blood-brain barrier (iBBB), a multicellular integrated human brain tissue (miBrain), "just add neurons" (JANs), or an induced minimal microvascular cell combo (miVasC).

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 present invention provides a method and composition for generating basal forebrain cholinergic neurons (BFCNs). [Solution] A highly reproducible protocol for efficiently obtaining BFCNs from pluripotent stem cells (PSCs), including embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), provides a method and composition for generating BFCNs from stem cells, particularly BFCNs in which electrophysiological abnormalities associated with one or more mutations in PSEN2 have been repaired, as well as the use of such BFCNs in cell-based therapies for treating Alzheimer's disease. TIFF2026108846000021.tif41148

The present invention relates to a human ectoderm derived brain cell characterized by the following features: (1) the intron between exons 10 and 11 of the MAPT gene encoding the Tau protein has been removed by genome-editing from one or both allele(s); and (2) at least one of the alleles of the MAPT gene of (1) carries at least one mutation enhancing Tau aggregation and at least one mutation enhancing nucleation of Tau aggregation; or (3) one allele of the MAPT gene as defined in claim 1(1) carries at least one mutation enhancing Tau aggregation, preferably in exon 10, and the other allele carries at least one mutation enhancing nucleation of Tau aggregation, preferably in exon 11.

Systems and techniques are provided for making genetically engineered ion channels (ICs) with bioluminescent resonance energy transfer (BRET) complexes and using such ICs for efficient readout of neural activity and output of biological neuronal networks.SOLUTION: In one implementation, the disclosed technology includes identifying a target location in the IC for expression of a target protein including a donor tag protein and an acceptor tag protein, and modifying the genome of the neuronal cell at a portion associated with the target location in the IC. The technique further includes causing the neuronal cell to express the target protein in the IC according to the modified genome. In the first (second) state of the IC, the donor tag protein is at a first (second) distance from the acceptor tag protein that is related to the absence (presence) of energy transfer between the donor tag protein and the acceptor tag protein.SELECTED DRAWING: Figure 3A-3C

Methods are provided for generating pre-oligodendrocyte precursor cells (pre-OPCs), oligodendrocyte precursor cells (OPCs), and pre-myelinating oligodendrocytes (pre-OLs) from human pluripotent stem cells using chemically defined culture media, which allow for the generation of pre-OPCs in as little as 3 days, SOX10+ OLIG2+ NKX2-2+ OPCs in as little as 12 days, and CD9+ A2B5+ O4+ CNPase+ pre-OLs in as little as 18 days. Two alternative culture protocols for generating OPCs are provided. Culture media, isolated cell populations, and kits are also provided.