162 results about "Astrocyte" 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.

Methods, compositions and kits for producing functional neurons, astroctyes, oligodendrocytes and progenitor cells thereof are provided. These methods, compositions and kits find use in producing neurons, astrocytes, oligodendrocytes, and progenitor cells thereof for transplantation, for experimental evaluation, as a source of lineage- and cell-specific products, and the like, for example for use in treating human disorders of the CNS. Also provided are methods, compositions and kits for screening candidate agents for activity in converting cells into neuronal cells, astrocytes, oligodendrocytes, and progenitor cells thereof.

The present invention is directed to a combination of therapeutic compounds and treatment methods and kits using the combination. In particular, one of the combination affects the NCca-ATP channel of neural tissue, including neurons, glia and blood vessels within the nervous system. Exemplary SUR1 and / or TRPM4 antagonists that inhibit the NCca-ATP channel may be employed in the combination. The combination therapy also employs one or more of a non-selective cation channel blocker and / or an antagonist of VEFG, NOS, MMP, or thrombin. Exemplary indications for the combination therapy includes the prevention, diminution, and / or 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, for example. In other embodiments, there are methods and compositions directed to antagonists of TRPM4, including at least for therapeutic treatment of traumatic brain injury, cerebral ischemia, central nervous system (CNS) damage, peripheral nervous system (PNS) damage, cerebral hypoxia, or edema, for example.

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.

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.

The invention which relates to the medicinal field discloses an application of butylphthalide and derivatives thereof in the preparation of medicines for preventing and treating ALS (amyotrophic lateral sclerosis). Butylphthalide and the derivatives, which can delay the disease time of an SOD1-G93A transgenic mouse, prolong the lifetime of the mouse, reduce the degenerative change of spinal motorneurons, obviously increase the survival number of spinal anterior horn motor neurons of the mouse, reduce the electrophysiological abnormality of the transgenic mouse, obviously improve the action potential amplitude and the motion unit number of compound muscles, substantially inhibit the activation of astrocytes and microglial cells in the spinal cord of the mouse, and obviously reduce the expression level of iNOS and NF-kappaBp65, have good application prospects in the prevention and the treatment of the ALS.

A method for identifying low grade astrocytoma cells in a sample is provided, wherein the method distinguishes between low grade astrocytoma cells and normal astrocytes, thus permitting early diagnosis of astrocytoma. The method uses antibody directed against J1-31 to test astrocytes in the sample for the presence or absence of J1-31 polypeptide, the low grade astrocytoma cells being characterized by the absence of J1-31 while normal astrocytes are characterized by the presence of J1-31.

An isolated expandable human neural stem or progenitor cell wherein the cell is a progenitor cells or stem cell, maintains its capability to differentiate into neurons, astrocytes, and oligodendrocytes, maintains its ability to differentiate into oligodendrocyte lineage cells efficiently throughout subsequent passages, and the cell expresses at least cell surface antigens CD133 and CD140α. Also provided is a method of in vitro culturing an expandable neural progenitor or stem cell isolated from a mammalian central nervous system, and the culture itself, wherein said cell maintains its capability to differentiate into neurons, astrocytes, and oligodendrocytes and its ability to differentiate into oligodendrocyte-lineage cells efficiently. In addition, a method of treating a condition caused by a loss of myelin or a loss of oligodendrocytes is provided as is a composition comprising an isolated expandable neural stem cell or one cultured by the methods of the invention.

Current sources of neural stem and progenitor cells for neural transplantation are essentially inaccessible in living animals. This invention relates to neural precursor cells (stem cells, progenitor cells or a combination of both types of cells) isolated from the olfactory epithelium of mammals that can be passaged and expanded, and that will differentiate into cell types of the central nervous system (CNS), including astrocytes, oligodendrocytes, and tyrosine-hydroxylase-positive neurons. These precursor cells provide an accessible source for autologous transplantation in CNS, PNS, spinal cord and other damaged tissues.

Methods, compositions and kits for producing functional neurons, astroctyes, oligodendrocytes and progenitor cells thereof are provided. These methods, compositions and kits find use in producing neurons, astrocytes, oligodendrocytes, and progenitor cells thereof for transplantation, for experimental evaluation, as a source of lineage- and cell-specific products, and the like, for example for use in treating human disorders of the CNS. Also provided are methods, compositions and kits for screening candidate agents for activity in converting cells into neuronal cells, astrocytes, oligodendrocytes, and progenitor cells thereof.

The invention discloses tissue-engineered neural tissues and a construction method thereof, belonging to the technical field of tissue engineering and regeneration medicine. Subcultured and purified neural stem cells serve as seed cells of the tissue-engineered neural tissues, a liquid type I collagen and Matrigel matrix serves as stent materials, and the seed cells and the stent materials are cultured after being compounded in vitro. A stent system adopted in the invention can be used for effectively maintaining the survival and proliferation of the neural stem cells, promoting the differentiation of the neural stem cells, and forming engineered neural tissues consisting of mature neurons, astrocytes and oligodendrocytes. The tissue-engineered neural tissues have an important significance in treating neural system injury through the transplantation of the tissue-engineered neural tissues, and can also serve as an in-vitro model for the psychological research of neurodevelopment, cerebral trauma and neuroelectricity.

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.

Cultures of cells immunoreactive for glial fibrillary acidic protein (GFAP), as well as for the intermediate filament marker nestin were grown in a medium including epidermal growth factor (EGF) and serum. The cultured cells had the morphology of astroglial cells. The cells can be proliferated in adherent or suspension cultures. Depending on the culture conditions, the cells can be induced to differentiate to neurons or glial cells. The cultures can be expanded over a large number of passages during several months, and survive, express an astroglial phenotype and integrate well after transplantation into both neonatal and adult rat forebrain.

The invention is based on the discovery that STM / Hop promotes proliferation of human glioblastoma-derived cells but not of normal astrocytes and that the proliferation requires the binding of STM / Hop to PrPC. The invention is directed to methods for treating cancer which rely on interfering with the Hop-PrPC interaction and to peptides, and antibodies raised against the peptides, which directly provide that interference. The invention is further based on the discovery that STI1230-245 peptide and its human homologue Hop23o-245 provide the desired interference with the STI1 / Hop-Pre interaction and inhibit the STI 1 / Hop-induced proliferation of glioma and glioblastoma cells. The invention is thus further directed to methods of treating cancer that employ these peptides and functional derivatives thereof, and antibodies directed to the peptides and derivatives. The invention is further directed to means of treating cancer which involve reducing the effective amount of Hop or reducing the expression of Hop. The invention is further directed to means of alleviating or eliminating the side effects of drug therapy and radiotherapy used in treating patients with brain cancers.

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.

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 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 relates to pharmaceutical compositions, kits, methods, and uses for the treatment of amyotrophic lateral sclerosis. In particular, the invention relates to pharmaceutical compositions, kits, methods, and uses for the treatment of amyotrophic lateral sclerosis by decreasing the expression of a cytoplasmic granule toxin in astrocytes of a patient, or by increasing the expression of MHC class I in motor neurons of the patient.

The present invention relates to an angiogenesis inhibitor comprising meteorin as an active ingredient that is highly expressed in astrocytes of the brain and retina in the late embryonic stage and after the birth of a mouse. It is in particular highly detected in astrocyte endfeet surrounding blood vessels and promotes the expression of thrombospondin-1 / -2 (TSP-1 / -2) via autocrine pathway and thus inhibits angiogenesis. The meteorin of the present invention can be effectively used for pharmaceutical compositions and health foods that prevent vascular diseases by inhibiting angiogenesis.

The invention relates to an astrocyte separating and cultivating method, which is appropriate for various experimental animals and human. The method mainly aims at the problems in the prior art, and improves the method for separating and cultivating astrocyte in vitro at present. The method comprises five experimental steps: cerebral cortex tissue separation, filtering by a seive after tissue cell trituration, cell primary culture, continuous cell culture, and astrocyte identification. The whole method is simple and practicable. Purity of the astrocyte cultivated and obtained by the method reaches more than 95% and the astrocyte grows well, is rapid in cell proliferation, and can be continuously cultured for many times and meets the demand of various experiments of cytobiology.

The invention discloses novel application of a medicine - curcumin, namely application of the curcumin in preventing and treating or treating the Parkinson disease. After the curcumin acts on an MPTP-constructed Parkinson disease mouse model, the curcumin can effectively promote expression of tyrosine hydroxylase in substantia nigra, lighten damage of sneurotoxin on the tyrosine hydroxylase in substantia nigra, reduces damage of dopaminergic neurons, promote biosynthesis of damaged dopamine and promote restoration and growth of damaged dopaminergic neurons; the curcumin can also inhibit astrocytes to secrete gelatinous fiber proteins, reduce stimulus of the neurotoxin on the astrocytes and lighten phlegmonosis of a brain tissue; moreover, the curcumin can inhibit expression of induction type nitrous oxide synthase, lighten induction of the neurotoxin on the induction type nitrous oxide synthase and inhibit reinforcement of intracephalic oxidative stress reaction. Therefore, the curcumin can effectively reduce damage of the dopaminergic neurons, thereby having significant potential value in developing medicines for preventing and treating and / or treating the Parkinson disease.

The invention relates to pharmaceutical compositions, kits, methods, and uses for the treatment of amyotrophic lateral sclerosis. In particular, the invention relates to pharmaceutical compositions, kits, methods, and uses for the treatment of amyotrophic lateral sclerosis by decreasing the expression of a cytoplasmic granule toxin in astrocytes of a patient, or by increasing the expression of MHC class I in motor neurons of the patient.

The invention provides a method for inducing neural stem cells by use of non-integrated plasmid vectors. The method comprises the steps of extraction of mononuclear cells from blood, expansion of the mononuclear cells in blood, electrotransfection of non-integrated plasmids and culture of neural stem cells. Mononuclear cells in human peripheral blood are reprogrammed into the neural stem cells which can be expanded by 60 generations or above in vitro to express related genes of the neural stem cells, nerve cells, astrocytes and oigodendrocytes can be differentiated, and the differentiated nerve cells have the electrophysiological characteristic. The method is simple to operate and extremely less in trauma.

Soluble proteins, e.g. thrombospondins, can trigger synapse formation. Such proteins are synthesized in vitro and in vivo by astrocytes, which therefore have a role in synaptogenesis. These thrombospondins are only expressed in the normal brain exactly during the period of developmental synaptogenesis, being off in embryonic brain and adult brain but on at high levels in postnatal brain. Methods are provided for protecting or treating an individual suffering from adverse effects of deficits in synaptogenesis, or from undesirably active synaptogenesis. These findings have broad implications for a variety of clinical conditions, including traumatic brain injury, epilepsy, and other conditions where synapses fail to form or form inappropriately. Synaptogenesis is enhanced by contacting neurons with agents that are specific agonists or antagonists of thrombospondins. Conversely, synaptogenesis is inhibited by contacting neurons with inhibitors or antagonists of thrombospondins.

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.

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.

Isolated, mammalian, adult bone marrow-derived, lineage negative hematopoietic stem cell populations (Lin− HSCs) contain endothelial progenitor cells (EPCs) capable of rescuing retinal blood vessels and neuronal networks in the eye. Preferably at least about 20% of the cells in the isolated Lini HSCs express the cell surface antigen CD31. The isolated Lin− HSC populations are useful for treatment of ocular vascular diseases and to ameliorate cone cell degeneration in the retina. In a preferred embodiment, the Lin− HSCs are isolated by extracting bone marrow from an adult mammal; separating a plurality of monocytes from the bone marrow; labeling the monocytes with biotin-conjugated lineage panel antibodies to one or more lineage surface antigens; removing of monocytes that are positive for the lineage surface antigens from the plurality of monocytes, and recovering a Lin− HSC population containing EPCs. The isolated Lin− HSCs also can be transfected with therapeutically useful genes. The treatment may be enhanced by stimulating proliferation of activated astrocytes in the retina using a laser.