35 results about "Fibrillary astrocytes" patented technology

The present invention is directed to therapeutic compounds, treatment methods, and kits affecting the NCCa-ATP channel of neural tissue, including neurons, glia and blood vessels within the nervous system, and methods of using same. The NCCa-ATP channel is newly expressed in neural tissue following injury such as ischemia, and is regulated by the sulfonylurea receptor SUR1, being inhibited by sulfonylurea compounds, e.g., glibenclamide and tolbutamide, and opened by diazoxide. Antagonists of the NCCa-ATP channel, including SUR1 antagonists, are useful in the prevention, diminution, and treatment of injured or diseased neural tissue, including astrocytes, neurons and capillary endothelial cells, that is due to ischemia, tissue trauma, brain swelling and increased tissue pressure, or other forms of brain or spinal cord disease or injury. Agonists of the NCCa-ATP channel may be are useful in the treatment neural tissue where damage or destruction of the tissue, such as a gliotic capsule, is desired.

An astrocyte-specific drug carrier containing a retinoid derivative and / or a vitamin A analog as a constituent; a drug delivery method with the use of the same; a drug containing the same; and a therapeutic method with the use of the drug. By binding a drug carrier to a retinoid derivative such as vitamin A or a vitamin A analog or encapsulating the same in the drug carrier, a drug for therapeutic use can be delivered specifically to astrocytes. As a result, an astrocyte-related disease can be efficiently and effectively inhibited or prevented while minimizing side effects. As the drug inhibiting the activity or growth of astrocytes, for example, a siRNA against HSP47 which is a collagen-specific molecule chaperone may be encapsulated in the drug carrier. Thus, the secretion of type I to type IV collagens can be inhibited at the same time and, in its turn, fibrosis can be effectively inhibited.

This invention relates to human adipose tissue-derived multipotent adult stem cells. More particularly, the invention relates to human adipose tissue-derived multipotent stem cells, which can be maintained in an undifferentiated state for a long period of time by forming spheres and have high proliferation rates, as well as methods for isolating and maintaining the adult stem cells, and methods for differentiating the multipotent adult stem cells into nerve cells, fat cells, cartilage cells, osteogenic cells and insulin-releasing pancreatic beta-cells. Also, the invention relates to cellular therapeutic agents for treating osteoarthritis, osteoporosis and diabetes and for forming breast tissue, which contain the differentiated cells or the adult stem cells. Although the multipotent stem cells are adult stem cells, they have the ability to differentiate into osteogenic cells, nerve cells, astrocytes, fat cells, chrondrogenic cells or insulin-releasing pancreatic beta-cells, and so are effective in treating osteoporosis, osteoarthritis, nerve disease, diabetes, etc. Also, the stem cells form spheres in a serum-free medium containing CORM-2, and thus can be maintained in an undifferentiated state for a long period of time. Also, the stem cells have very high proliferation rates. Accordingly, the stem cells are useful as cellular therapeutic agents.

Adult neural stem cells differentiate into neurons, astrocytes, and oligodendrocytes in the mammalian CNS, but the molecular mechanisms that control their differentiation are not yet well understood. Insulin-like growth factor-I (IGF-I) can promote the differentiation of cells already committed to an oligodendroglial lineage during development. However, it is unclear whether IGF-I affects multipotent neural stem cells. Here we show that IGF-I stimulates the differentiation of multipotent adult rat hippocampus-derived neural progenitor cells into oligodendrocytes. Modeling analysis indicates that the actions of IGF-I are instructive. Oligodendrocyte differentiation by IGF-I appears to be mediated through an inhibition of BMP signaling. Furthermore, overexpression of IGF-I in the hippocampus leads to an increase in oligodendrocyte markers. These data demonstrate the existence of a single molecule, IGF-I, that can influence the fate choice of multipotent adult neural progenitor cells to an oligodendroglial lineage.

In one embodiment, the present invention is a method of creating a fully-human blood-brain barrier (BBB) model, comprising the steps of (a) obtaining a mixture of neural cells and brain microvascular endothelial cells (BMECs), wherein the neural cells and BMECs that comprise the mixture were produced from the differentiation of human pluripotent stem cells (hPSCs); (b) purifying BMECs from the mixture of neural cells and BMECs of step (a); and (c) co-culturing the purified BMECs with a cell type selected from the group consisting of pericytes, astrocytes and differentiated neural progenitor cells (NPCs), wherein a blood brain barrier model is created.

A method of preserving cone cells in the eye of a mammal suffering from a retinal degenerative disease comprises isolating from the bone marrow of the mammal a lineage negative hematopoietic stem cell population that includes endothelial progenitor cells, transfecting cells from the stem cell population with a gene that operably encodes an antiangiogenic fragment of human tryptophanyl tRNA synthetase (TrpRS), and subsequently intravitreally injecting the transfected cells into the eye of the mammal in an amount sufficient to inhibit the degeneration of cone cells in the retina of the eye. The treatment may be enhanced by stimulating proliferation of activated astrocytes in the retina using a laser.

It is intended to provide a screening system for a centrally acting drug transported across the blood-brain barrier, a drug acting on the blood-brain barrier itself, or a drug transferred into the brain without being expected to centrally act. Moreover, another object of the present invention is to achieve pathogenesis analysis study or the screening in a diseased state by applying various diseased environments to this screening system. The present invention provides an in-vitro model of blood-brain barrier obtained by using a three-dimensional culture apparatus comprising: a culture solution; a plate holding the culture solution; and a filter immersed in the culture solution and placed in no contact with the inside bottom of the plate, the filter having plural pores of 0.35 to 0.45 μm in diameter, and by comprising: seeding primary cultured brain capillary endothelial cells onto the upper surface of the filter; seeding primary cultured brain pericytes onto the under surface of the filter; seeding primary cultured astrocytes onto the inside surface of the plate; and coculturing these cells in a normal culture solution.

The present invention is directed to therapeutic compounds, treatment methods, and kits affecting the NCCa-ATP channel of neural tissue, including neurons, glia and blood vessels within the nervous system, and methods of using same. The NCCa-ATP channel is newly expressed in neural tissue following injury such as ischemia, and is regulated by the sulfonylurea receptor SUR1, being inhibited by sulfonylurea compounds, e.g., glibenclamide and tolbutamide, and opened by diazoxide. Antagonists of the NCCa-ATP channel, including SUR1 antagonists, are useful in the prevention, diminution, and treatment of injured or diseased neural tissue, including astrocytes, neurons and capillary endothelial cells, that is due to ischemia, tissue trauma, brain swelling and increased tissue pressure, or other forms of brain or spinal cord disease or injury. Agonists of the NCCa-ATP channel may be are useful in the treatment neural tissue where damage or destruction of the tissue, such as a gliotic capsule, is desired.

The invention discloses an in-vitro construction method for simulating a blood brain barrier through human brain microangiogenesis. The method comprises the following steps: preparing human brain microvascular endothelial cell suspension and human astrocyte suspension, and preparing fibrinogen mother liquor and thrombin mother liquor; mixing the endothelial cell suspension, the astrocyte suspension, a DMEM (Dulbecco's Modified Eagle Medium) medium, the fibrinogen mother liquor and the thrombin mother liquor, and preparing a mixed cell gel solution; injecting the mixed cell gel solution into amicro-fluidic chip, performing thermostatic incubation to gelation, adding an endothelial growth medium into the micro-fluidic chip, and constructing a 3D cell culture chip; performing continuous culture on the 3D cell culture chip, and enabling the endothelial cells and astrocyte to grow into a brain microvascular network structure, namely correspondingly producing the simulated blood brain barrier. According to the technical scheme provided by the invention, the in-vitro model of the blood brain barrier is successfully constructed, and the characteristics of the blood brain barrier are clearly and accurately reflected.

Compositions and methods are provided for the purification of astrocytes from biological samples or from in vitro cultures. An advantage of the methods of the invention is the ability to isolate astrocytes in a quiescent state, which allows analysis of the cells in a more natural state.

This document provides methods and materials for generating GABAergic neurons in brains. For example, methods and materials for using nucleic acid encoding a NeuroD1 polypeptide and nucleic acid encoding a Dlx2 polypeptide to trigger glial cells (e.g., NG2 glial cells or astrocytes) within the brain (e.g., striatum) into forming GABAergic neurons (e.g., neurons resembling medium spiny neurons such as DARPP32-positive GABAergic neurons) that are functionally integrated into the brain of a living mammal (e.g., a human) are provided.

The present invention provides a method of differentiating and proliferating a mesenchymal stem cell into the neural cell by culturing in a medium comprising an epidermal growth factor and a hepatocyte growth factor after confluent culture of the mesenchymal stem cell. The present invention provides more effective method of differentiating and proliferating the mesenchymal stem cell or the mononuclear cell comprising the mesenchymal stem cell into the neural cell with a neuron and an astrocyte in terms of time, efficiency and maturity as compared with conventional methods.

The present invention provides a method of differentiating and proliferating a mesenchymal stem cell into the neural cell by culturing in a medium comprising an epidermal growth factor and a hepatocyte growth factor after confluent culture of the mesenchymal stem cell. The present invention provides more effective method of differentiating and proliferating the mesenchymal stem cell or the mononuclear cell comprising the mesenchymal stem cell into the neural cell with a neuron and an astrocyte in terms of time, efficiency and maturity as compared with conventional methods.

A method of preparing neural precursor cells by exposing pluripotent stem cells or neural stem cells to a differentiation agent. The agent is a pyridine analog, which in preferred embodiments is a phenylethynyl-substituted or phenylazo-substituted pyridine. In other embodiments, a method of enhancing neural precursor cell survival is provided in which the survival is enhanced by exposure to the pyridine analog. In further embodiments, a method of preparing neuronal cells is provided in which pluripotent or neural stem cells exposed to the pyridine analog are then incubated without the pyridine analog, resulting in differentiation into neurons, astrocytes and oligodendrocytes. These methods may be used in toxicological screens, e.g., to evaluate the neurotoxicity of a test compound.

The present invention relates to an immortalised human neural precursor cell line, NGC-407. The cell line has been established from human foetal tissue. The cell line has been immortalised using a retroviral vector containing the v-myc oncogene. The cell line is a neural progenitor cell line capable of differentiating into to astrocytes and neurons including dopaminergic neurons. NGC-407 cells are capable of migrating to glioblastoma tumours implanted into rat brains and form gap junctions with the tumour cells. NGC-407 cells expressing a suicide gene can be be used for delivering activated prodrugs in the form of activated nucleoside analogs to tumours.

The invention provides a three-channel microfluidic chip for establishing three kinds of cell in-vitro co-culture models. The three-channel microfluidic chip is characterized by comprising three flow channels capable of being used for inoculating different element cells respectively, and tiny flow channels which are designed for communication among different cells, and connected between each two flow channels in a communication manner; astrocytes in a nervus vascularis unit are taken as a bridge, and role the important role of communicating nerve cells and cerebral microvascular endothelial cells, therefore, the astrocytes are inoculated in the middle flow channel. The three-channel microfluidic chip has the advantages that (1) the nervus vascularis unit models established by the three-channel microfluidic chip can truly show the real framework in the brain of which the astrocytes are taken as the bridge and are connected with the other two element cells together, namely, nerve cells-astrocytes-cerebral microvascular endothelial cells; and (2) the three-channel microfluidic chip can represent the O2 of different concentrations, so to as further reflect the ischemic hypoxemia states of the three element cells in the nervus vascularis unit after the oxygen-glucose deprivation damage.

The invention discloses an immortalized human neural stem cell line and a preparation method thereof. The method comprises the following steps: (1) isolating and culturing primary human hippocampus-derived neural stem cells; (2) constructing a recombinant lentiviral vector containing L-myc gene; (3) carrying out packaging production of the above recombinant lentiviral and collecting supernatant; (4) selecting virus supernatant with appropriate concentration for transfection and screening of stem cells and constructing the immortalized human neural stem cell line. The preparation method of immortalized cell line provided by the invention is a novel stable and safe and effective immortalized coding strategy; the prepared immortalized human neural stem cell line has all the biological characteristics of primary neural stem cells, and also has the feature of normal three-line differentiation at the same time, can be successfully differentiated into neurons, astrocytes and oligodendrocytes,and the growth rate of such cell line and ability to form neurospheres are stronger than the growth rate of primary cells, and the cell line can still proliferate rapidly after 20 generations withouttumorigenicity.

The invention features a non-transgenic rat model for early AD, using a metal mixture of As, Cd and Pb, characterized by enhanced synergistic amyloidogenicity in rat cortex and hippocampus. This model can serve as a tool for (a) AD-directed drug screening, and (b) determining mechanism of AD pathogenicity. It features induction of the A?-mediated apoptosis and induction of inflammation in rodent brain. The invention features novel astrocyte and neuronal cellular models for AD, using a metal mixture of As, Cd and Pb, characterized by enhanced synergistic amyloidogenicity. This model can serve as a tool for (a) AD-directed drug screening in astrocytes and neurons, and (b) determining mechanism of AD pathogenicity in cells. It features induction of the A?-mediated apoptosis and induction of inflammation in astrocytes and neurons.

Multipotent neuroepithelial stem cells and lineage-restricted oligodendrocyte-astrocyte precursor cells are described. The neuroepithelial stem cells are capable of self-renewal and of differentiation into neurons, astrocytes, and oligodendrocytes. The oligodendrocyte-astrocyte precursor cells are derived from neuroepithelial stem cells, are capable of self-renewal, and can differentiate into oligodendrocytes and astrocytes, but not neurons. Methods of generating, isolating, and culturing such neuroepithelial stem cells and oligodendrocyte-astrocyte precursor cells are also disclosed.

Disclosed herein are kits comprising transcription factors for inducing a fibroblast cell into an induced embryonic neural progenitor cell. The induced embryonic neural progenitor cell is then capable of differentiating into an astrocyte, an oligodendrocyte or a neuron. Also disclosed are the uses of the kit as a platform for selecting a drug candidate to treat neurological diseases.

The present invention investigate the two modes of glutamate release and the releasing rate of glutamate, and thus can provide a useful technique for neuron protection and acceleration of neurotransmission by controlling the glutamate release in astroctye. Thus, the present invention provides an inhibitor of the fast-mode release and / or the slow-mode release of astrocytic glutamate, a screening method of the inhibitor and a pharmaceutical composition or method of ameliorating, preventing and / or treating the disease associated with the over-release of glutamate via the Ca2+-activated anion channel, with the inhibition of fast-mode glutamate release.

The present invention relates to methods for modulating, disrupting or enhancing the clearance of copper / zinc superoxide dismutase 1 (SOD1) aggregates in astrocytes or motor neurons in a subject, by administering a medicament comprising a therapeutically effective amount of a cyclohexanehexyl derivative. In another aspect, the invention provides a medicament comprising at least one cyclohexanehexyl derivative of formula III or IV useful in preventing or treating amyothropic lateral sclerosis (ALS), improving motor neuron function and slowing the degeneration or death of motor neurons in brain stem, spinal cord or motor cortex. These medicaments may be administered orally, intravenously, intraperitoneal, subcutaneous, intramuscular, intranasal or transdermal.

The present invention relates to a viral vector for silencing a gene specifically in astrocytes comprising: —an astrocyte-specific viral envelope protein, —a first nucleic acid sequence encoding a transcription activator and at least one target sequence of a neuron-specific miR under the control of an astrocyte-specific promoter, and—a second nucleic acid sequence encoding a RNA for silencing the gene under the control of a promoter inducible by the transcription activator.

Methods for producing a population of human-derived glial restricted progenitor cells (GRPs) with decreased potentially unintended or undesired cellular phenotypes and / or decreased standard deviation in the cells of the population are provided. Also provided are antibody panels and gene expression profiles to characterize GRPs and a method for its use in characterizing GRP cells. In addition methods for use of these GRP cells to generate astrocytes and / or oligodendrocytes, to re-myelinate neurons and to treat glial cell related and other neurodegenerative diseases or disorders or injuries or damage to the nervous system are provided. A method to manufacture neural cells depleted of A2B5 positive cells is also provided.

The invention discloses a preparation method and culture medium of human-derived astrocyte precursor cells. The method can be utilized to obtain abundant astrocyte precursor cells in vitro. Compared with the traditional method of directly differentiating astrocyte cells from nerve stem cells, the precursor cells obtained by the method have high multiplication capacity and capacity for directional differentiation into astrocyte cells, and the method can quickly obtain abundant high-purity astrocyte cells in a short time. The culture medium for culturing astrocyte precursor cells has the characteristics of definite components and accessible commercial products. The method for generating abundant astrocyte cells for scientific research or clinic use has the characteristics of low cost, high safety, high production efficiency and high operability.

The invention relates to application of a dcf1 gene to regulation and control over expression of ATP1B1. Two types of mouse detection including a wild type (as reference) and dcf1 knockout are adopted, and it is found that the dcf1 gene has influences on astrocytes through ATP1B1; it is found through cell immunofluorescence observation that after dcf1 knockout is conducted, the sizes of the astrocytes are reduced; then cellular immunofluorescence and co-immunoprecipitation prove the interaction between DCF1 and the ATP1B1 with the function of influencing the sizes of the astrocytes, research on the interaction relationship and the upstream and downstream adjustment relationship between the DCF1 and the ATP1B1is conducted, meanwhile, an RNA interference technology is utilized to lower the expression quantity of the ATP1B1, it is observed that abnormity of the astrocytes is relieved, and the treatment potential of the DCF1 for dysgnosia caused by abnormity of the astrocytes is finally proved.