72 results about "Schwann cell" patented technology

The invention discloses an electrical stimulation type nerve regeneration method based on calcium signal regulation and control, and relates to the technical field of electrical stimulation type nerve regeneration, and the method comprises the following steps: based on a Schwann cell population calcium signal response feature set, identifying whether the calcium ion concentration is in a microliter stage which breaks through a lowest activation threshold and does not reach a stable state; judging whether the target nervous tissue is in a calcium signal activation critical state or not based on the behavior mode change of the Schwann cell population; based on the judgment result of the calcium signal activation critical state, an electrical stimulation adjustment control instruction is generated in real time in combination with the calcium ion concentration fluctuation trend and Schwann cell population response characteristics, and the calcium ion concentration stability is optimized and the activation state is maintained by adjusting the electrical stimulation intensity, the electrical stimulation pulse width, the electrical stimulation waveform type and the electrical stimulation application time sequence. According to the method, the problem that a calcium signal is difficult to recognize and dynamically optimize in a microliter stage is solved, and precise maintenance of Schwann cell activation and improvement of nerve regeneration efficiency are realized.

A cellularized nerve regeneration graft is disclosed that includes an electrospun biodegradable polymer conduit having an exterior surface and an interior luminal space, a plurality of fibroblasts seeded to the exterior surface of the conduit, and a system filling the interior luminal space of the conduit. The system may include a hydrogel matrix or augmented hydrogel matrix and Schwann cells. The cellularized nerve regeneration graft may be used in the repair of peripheral nerve injuries. Methods of making the cellularized nerve regeneration graft are also disclosed.

Disclosed are drug conjugates comprising a targeting moiety conjugated to a drug molecule, wherein the targeting moiety binds to a cell adhesion moiety and / or receptor expressed on a Schwann cell to mediate targeted delivery of the drug conjugate to the Schwann cell, and wherein the drug molecule modifies expression or activity of a disease-associated molecule, and / or confers a cytotoxic effect, in the Schwann cell. Further disclosed herein are methods of targeted delivery of a drug to the Schwann cells.

The invention discloses a trigeminal neuralgia treatment method, and relates to the technical field of trigeminal neuralgia treatment. The direct effect of the M2 on the proinflammatory and pain induction characteristics of the Schwann cells can play an important role in the multi-aspect analgesic effect of the M2; the microenvironment around nerves can be changed by increasing m < 2 > m macrophages after SHED-CM, so that NP is cured; immunohistochemical analysis shows that the number of p near-end side CD206 + F4 / 80 + macrophages of qualified thiocyanate is remarkably increased through sheet-CM treatment, however, TNF-alpha + S100beta + proinflammatory Schwann cells and TNF-alpha + F4 / 80 + M1 macrophages are remarkably reduced after sheet-CM treatment.

The invention discloses a functional polypeptide for promoting repair of endometrial stem cells to clitoris sensitive nerves and application, and belongs to the technical field of stem cell repair, the functional polypeptide is used for modifying the endometrial stem cells and Schwann cells through the functional polypeptide, and the clitoris sensitive nerves are repaired in a local slow-release gel delivery mode. The functional polypeptide can activate Laminin expression and regulate and control ECM degradation balance, so that collagen deposition in scar tissues is reduced; in addition, the functional polypeptide can effectively inhibit HOXA1 expression, enhance the axon extension capacity and strengthen the axon microtubulin polymerization capacity of the nerve injury part, and the nerve repair efficiency and the function recovery quality are remarkably improved.

The invention provides application of tea catechin in preparation of a medicine for preventing and treating bortezomib-induced peripheral neuropathy. A plurality of in-vitro model results show that tea catechin can be used as a copper death inhibitor, remarkably improves related indexes of bortezomib-induced peripheral neuropathy, improves survival rates of Schwanton cells and SH-SY5Y, improves mitochondrial functions and cell cycle abnormalities of the Schwanton cells, reduces intracellular copper ion, cuprous ion and ATP levels, and can be used for preparing the copper death inhibitor for the peripheral neuropathy of the Bortezomib-induced peripheral neuropathy of the Bortezomib-induced peripheral neuropathy. Meanwhile, the death of Schwann cells and SH-SY5Y induced by the copper death inducer is reduced. In-vivo experiments show that the tea catechin plays a role in protecting functional damage of the bortezomib, and the tea catechin remarkably improves mechanical hyperalgesia, gait abnormality and pathological changes of myelin sheath and axon of mice caused by peripheral neuropathy induced by the bortezomib. The tea catechin can be used as a medicine for peripheral neuropathy induced by bortezomib, and has high clinical application value and development prospect.

The application discloses an active polypeptide and application thereof in treating diabetic peripheral neuropathy, and belongs to the technical field of biological polypeptide drugs. An amino acid sequence of the active polypeptide is QVWPDGFVGLAKLWI, which is obtained by step-by-step enzymatic extraction and purification from Morus alba L. which is a homology of medicine and food. The polypeptide can significantly inhibit oxidative stress, inflammatory infiltration and cell apoptosis of Schwann cells induced by a high-sugar environment, and repair the function of damaged nerve cells. Meanwhile, the polypeptide can effectively improve abnormal sciatic nerve conduction function of a diabetic model mouse. The active polypeptide can be used for preparing a drug for treating diabetic peripheral neuropathy, and provides a new candidate drug and research and development direction for the targeted treatment of diabetic peripheral neuropathy.

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.

The application discloses application of skin precursor cell induced Schwann cell derived vesicles (SKP-SC-EVs) in preparation of a product for treating Parkinson's disease, wherein the SKP-SC-EVs have a protective effect in rotenone or MPP+-induced cell injury, and in a MPTP-induced mouse Parkinson's disease model, the SKP-SC-EVs can be given by a nasal instillation method to improve the motor ability of the mouse and restore the olfactory function, and the product can be used for research and treatment of Parkinson's disease.

The invention belongs to the technical field of biological medicines, and particularly provides application of Schwann cell exosomes in preparation of medicines for treating osteoporosis. An exosome derived from Schwann cells is prepared, and the inhibition effect of SC-EXO on osteoclasts is proved through TRAP staining, immunofluorescence, bone resorption, RT-qPCR and other experiments on the cell molecule level; meanwhile, the effect of SC-EXO on reduction of bone loss of ovarian extirpation mice is determined through in-vivo experiments. According to the invention, osteoclast formation and bone resorption capability can be inhibited, bone loss of OVX mice can be reduced in vivo, and the compound can be used for treating osteoporosis and other related diseases.

The invention discloses siRNA capable of knocking down Pr18a9 gene expression and application of the siRNA, and relates to the technical field of biological medicine. The invention provides a positive-sense strand sequence and an antisense strand sequence of the siRNA, and the siRNA is used for preparing a preparation for promoting Schwann cell survival. According to the invention, the Prl8a9 gene of SCs is knocked down by virtue of a small interfering RNA technology; by improving the proliferation and migration capabilities of the Schwann cells, the apoptosis rate of the Schwann cells is reduced, and the survival rate of the Schwann cells is further improved. Meanwhile, a transcriptome sequencing technology is applied, key genes and pathways of Schwann cells treated by siPr18a9 are deeply excavated, and a theoretical support is provided for research on a repair mechanism after peripheral nerve injury.

The present invention discloses diagnostic and therapeutic markers for diabetic peripheral neuropathy and their applications. The diagnostic and therapeutic marker is eIF6. This invention, for the first time, discovers that upregulation of eIF6 in Schwann cells is closely associated with diabetic peripheral neuropathy. Targeted inhibition of eIF6 can effectively inhibit the progression of neuropathy, which is of great significance for the early diagnosis and treatment of diabetic peripheral neuropathy and for reversing the course of the disease. This invention develops a new method for diagnosing diabetic peripheral neuropathy and a new drug target for treating the disease.

Disclosed herein are drug conjugates comprising a targeting moiety conjugated to a drug molecule wherein the targeting moiety binds to a receptor expressed on Schwann cells to mediate targeted delivery of the drug conjugate to Schwann cells, and wherein the drug molecule modifies expression or activity of a disease-associated molecule in Schwann cells. Also disclosed herein are methods of targeted delivery of drugs to Schwann cells.

According to the invention, case samples are analyzed through immunofluorescence and immunohistochemistry, and the clinical correlation of co-localization of lactic acid and Schwann cells and lactic dehydrogenase and subtypes thereof in gastric cancer samples is determined clinically; the invention finds that the Schwann cell conditioned medium can promote gastric cancer lactylation, proliferation and migration by secreting lactic acid; shRNA is adopted to inhibit lactic acid transport of Schwann cells, so that gastric cancer lactylation, proliferation and migration can be inhibited; the invention discovers that the Schwann cell conditioned medium promotes the expression of gastric cancer cell lactic acid transporters MCT1 and MCT4; through RNA sequencing and western blot, it is found that the Schwann cell conditioned medium promotes gastric cancer lactylation and finally promotes GluT1 expression. The invention researches the influence of Schwann cells on the growth of gastric cancer cells, and finds that lactic acid secreted by the Schwann cells can obviously promote the lactic acid acidification of the gastric cancer H3K9 site, and further promotes the proliferation and migration of the gastric cancer cells by increasing the expression of gastric cancer GluT1, which may indicate the key mechanism of the relationship between the cancer cells and tricarboxylic acid cycle.

The invention provides a culture method of a neurofibroma organ. The balling culture medium of the neurofibroma organ comprises EGF (epidermal growth factor) and FGF (fibroblast growth factor) with the concentration of 200-250ng The organoid culture method comprises the following steps: digesting neurofibroma tissue blocks to prepare a single-cell suspension; the single-cell suspension is placed in a culture dish treated by polylysine, a Schwann cell culture medium is added to be cultured for 24 hours, the Schwann cell culture medium contains forsklin and beta-heragulin needed by Schwann cell enrichment, and Schwann cell enrichment liquid is obtained; collecting Schwann cell enrichment liquid, adding the balling culture medium and Y-27632, culturing for 6-12 hours, collecting cells, adding the balling culture medium, and culturing for 7-14 days. The tumor ball culture method comprises the following steps: culturing the organoid according to the method, digesting the organoid and culturing. According to the present invention, the Schwann cell screening step is added, the components of the balling culture medium are improved, and the Y-27632 is added, such that the problems of small tumor ball number and small size are solved, and the stable neurofibroma organ can be formed.

The present invention relates to a pharmaceutical composition and cell therapy agent for the prevention or treatment of neurological diseases, comprising Schwann cell precursors (SCPs) or Schwann cells differentiated therefrom, derived from pluripotent stem cells (PSCs) or somatic cells, and natural killer (NK) cells as active ingredients. Specifically, the Schwann cell precursors (SCPs) express at least one selected from the group consisting of GAP43, SOX10, IGFBP2, and combinations thereof; the Schwann cells (SCs) express at least one selected from the group consisting of S100B, SOX10, and combinations thereof; and the natural killer (NK) cells express CD56 + CD16 + It is characterized by expressing at least one selected from the group consisting of the and combinations thereof.

The application discloses application of FTY720 as a PP2A phosphatase activator in preparation of a medicine for treating type I neurofibromatosis. The application first uses FTY720 for treatment of type I neurofibromatosis, and proves that FTY720 significantly inhibits formation of neurofibromas by non-specifically activating PP2A phosphatase. In-vivo experimental results show that FTY720 as a single drug can significantly inhibit tumor growth, and a synergistic effect is presented when FTY720 is combined with a MEK inhibitor, and tumor growth is almost completely inhibited. In-vitro cell experiments show that FTY720 as a single drug or in combination with MEKi treatment can inhibit tumor Schwann cells from forming tumor spheres, inhibit cell proliferation and migration, and induce tumor cell apoptosis. The application overcomes the drug resistance problem existing in the prior art MEK inhibitor, and provides a new treatment strategy for type I neurofibromatosis. FTY720 is an FDA-approved drug, and has good safety and drugability, and has high clinical conversion potential.

The invention relates to the field of biological medicine, in particular to a linear peptide with nerve growth factor biological activity and application. The invention provides NPL2m with a sequence as shown in SEQ ID NO: 1, experimental results show that the NPL2m has a remarkable promoting effect on proliferation and migration of a PC12 nerve cell line, extension of primary dorsal root ganglion axons and growth of Schwann cells can be remarkably promoted, in addition, the NPL2m can remarkably improve the motor function and nerve electrophysiological signal transduction of animals, the effect is similar to that of NGF, and the NPL2m can be used for preparing a medicine for preventing and treating the diseases of the animals. Therefore, the NPL2m disclosed by the invention can greatly reduce the cost and has higher stability while retaining the biological activity of the NGF.

The invention provides a composite active dressing for neural restoration and a preparation method and application thereof, and relates to the technical field of medical materials. The composite active dressing comprises a transdermal inner layer and a small extracellular vesicle slow-release outer layer, the transdermal inner layer is of a membrane-shaped structure and comprises a composite active component and a hydrogel matrix material, and the composite active component is selected from one or more of an anti-inflammatory component, a microcirculation improving component, an antioxidant component and a neurotrophic component; the small extracellular vesicle sustained-release outer layer is of a three-dimensional network structure and comprises small extracellular vesicles and a hydrogel matrix material. According to the invention, stable loading and layered deep delivery and release of the small extracellular vesicles are realized, the inflammatory response and microcirculation state of an injured part are improved, proliferation migration and remyelination of Schwann cells can be promoted, and axon regeneration and effective repair of nerve injury can also be promoted.

The invention belongs to the technical field of biological medicines, and particularly provides application of Schwann cell exosomes in preparation of osteoclast differentiation resisting medicines. Firstly, a Schwann cell and osteoclast precursor cell co-incubation experiment proves that Schwann cells inhibit osteoclast differentiation through exosomes. Then miRNA sequencing analysis is conducted on Schwann cell exosomes, then a PTEN / AKT signal channel is screened out, and experiments such as TRAP dyeing, RT-qPCR and WB are conducted on the cell molecule level to prove that SC-EXO inhibits osteoclast differentiation through the PTEN / AKT signal channel; meanwhile, through in-vivo experiments, the inhibition effect of SC-EXO on the osteoclast activity of ovarian-removed mice through a PTEN / AKT signal channel is determined. Therefore, the Schwann cell exosome can be used as an osteoclast differentiation inhibitor drug, and can be used as an osteoclast differentiation inhibitor for treating related diseases.

The application belongs to the technical field of nerve grafts, and discloses a multilayer composite capacitive film, a preparation method and application of the multilayer composite capacitive film in nerve repair scaffolds. The scaffold is composed of three layers, namely, an A layer, a B layer and an A layer. The A layer is a sandwiched layer on both sides, and comprises a mixture of chitosan (or silk fibroin or a decellularized matrix) and a conductive polymer PEDOT:PSS and a crosslinking agent polyethylene glycol diglycidyl ether (PEGDE). The B layer is a middle hydrogel sandwiched layer, and comprises methacrylated gelatin (Gel-MA). The A layers on both sides are bonded through the B layer to form a viscoelastic hydrogel after ultraviolet light irradiation, and the composite capacitive scaffold in a multilayer structure with a through middle cavity is obtained after curing and air drying. The formed scaffold has good electrical conductivity, mechanical properties and biological safety, and can effectively induce the proliferation, migration and differentiation of RSC96 Schwann cells and nerve system cells PC12, thereby providing a good physical stable support and a favorable microenvironment for peripheral nerve injury repair.

The invention belongs to the technical field of biological medicine, and particularly relates to application of circular RNA as a marker in detection of hand-foot-and-mouth disease complicated nerve injury. According to the invention, the application of the hsacirc0069335 as the marker in predicting the hand-foot-and-mouth disease complicated nerve injury is found for the first time. In an external verification queue, a serum sample of a patient with a nerve injury symptom does not contain the marker, and the area under an ROC curve of the marker is 1, so that the marker can be used as the marker of the hand-foot-and-mouth disease complicated with the nerve injury and has excellent specificity and sensitivity. Furthermore, it is found that EV71 infection inhibits growth of Schwann cells and damage of myelin sheath formation, resulting in significant injury of a nervous system, and the EV71 infection is related to hsacirc0069335 / miR-29b-3p / PMP22 pathway. The discovery may provide a key molecular target for early warning and treatment of the severe hand-foot-and-mouth disease, so that the development progress of treatment drugs is accelerated.

Disclosed are pharmaceutical compositions comprising the growth factor neuregulin 1 (NRG1). Further disclosed herein are methods of using neuregulin 1, or pharmaceutical compositions comprising NRG1, to treat or prevent neurotrophic keratitis, methods to induce corneal headlining in an eye of a subject that has been denervated, and methods or preventing death of Schwann cells in the cornea of a subject that has suffered a corneal denervation.

A compound for use in the treatment of CIDP, an immune-mediated or autoimmune disease of the peripheral nervous system, wherein the compound increases the resistance of Schwann cells and spinal ganglia to oxidative stress, containing propionic acid, its physiologically acceptable salts and / or esters with C1-C8 alkyl alcohols.

The present invention provides viral vectors for use in the treatment and prevention of diseases associated with Schwann cells by delivering polynucleotides specifically to Schwann cells and achieving Schwann cell specific expression. The present invention has particular application in treatment and prevention of Charcot-Marie-Tooth disease and other demyelinating neuropathies. The preferred vectors are adeno-associated vectors (AAV) having a Schwann cell-specific promoter from the Myelin Protein Zero (Mpz, P0) or a minimal Mpz promoter.

The invention relates to a method for evaluating ferroptosis sensitivity of NF2-related vestibular nerve sheath tumor Schwann cells. The method comprises the following steps: constructing NF2-mutated immortalized Schwann cells; carrying out ferroptosis induction and intervention experiments, and establishing a plurality of experiment groups; detecting ROS level, Fe < 2 + > concentration, GSH content, MDA level and protein expression of GPX4 and the like of each group of cells; sample preparation is carried out through a TEM method, and mitochondrial volume and morphological characteristics of each group of cells in a ferroptosis state are observed; detecting the cell viability, cell membrane damage and apoptosis proportion of each group of cells; and evaluating the influence of NF2 deletion on ferroptosis sensitivity. According to the method, a ferroptosis cell modeling scheme in which Erastin (an inducer) and Fer-1 (an inhibitor) are jointly intervened is designed, and a multi-dimensional ferroptosis evaluation system is combined, so that the stability and the result reproducibility of NF2 related vestibular nerve sheath tumor Schwann cell ferroptosis state evaluation are remarkably improved.

The invention discloses a method for inducing and differentiating Schwann cells by using olfactory ensheathing cells and mesenchymal stem cells. The method comprises the following steps: mixing adipose-derived mesenchymal stem cells and olfactory ensheathing cells for culturing, and inducing to obtain the Schwann cells. According to the method, the adipose-derived stem cells are differentiated into the Schwann cells through induction culture, the differentiation speed is high, and the functional Schwann cells with the remarkably increased number can be obtained.

The present invention aims to provide a method for obtaining Schwann cells directly (by direct reprogramming) without going through pluripotent stem cells such as ES cells or iPS cells. As a means for solving the above-mentioned problems, a method for preparing Schwann cells is provided, which comprises the step of introducing at least one gene selected from the group consisting of SOX10 gene and KROX20 gene or its expression product into somatic cells of a mammal.

The present invention relates to a system for regulating overexpression of PMP22 gene by a P1 promoter in patients with Charcot-Marie Tooth disease (CMT) to a normal level by using zinc finger protein (ZFP). Specifically, the present invention provides an isolated ZFP consisting of three or more zinc fingers and specifically reducing the expression of a PMP22 protein by a P1 promoter by binding to a promoter of the PMP22 gene or a part thereof in nervous system cells, or a polynucleotide encoding same. The present invention also provides novel transcriptional regulatory sequences for Schwann cell-specific expression of nucleic acid molecules encoding genes to be expressed in Schwann cells or proteins to be expressed in Schwann cells. The ZFP for regulating PMP22 gene expression according to the present invention or a polynucleotide encoding same can be used as a therapeutic agent for preventing or treating CMT disease, and can be more effectively expressed by the Schwann cell-specific transcriptional regulatory sequence.

The presently disclosed subject matter provides for in vitro methods of inducing differentiation of stem cells into Schwann cell precursors and Schwann cells, and Schwann cell precursors and Schwann cells generated by such methods. The presently disclosed subject matter also provides for uses of such Schwann cell precursors and Schwann cells for regeneration of PNS and / or CNS, for prevention and / or repair of myelin damages, and / or for prevention and / or treatment of Schwann cell related disorders (e.g., peripheral neuropathy, e.g., Diabetic Peripheral Neuropathy).