55 results about "Sonic hedgehog" patented technology

The present invention relates to compounds, small interfering RNAs and compositions and methods of inhibiting tumorigenesis using agents that inhibit the sonic hedgehog and GLI signaling pathway, including agents that inhibit GLI expression, synthesis and / or function. The present invention also relates to particular biomarkers that can be used in the diagnosis and prognosis of cancer. Methods of treating cancer, including glioblastomas, medulloblastomas, basal cell carcinomas, prostate cancer and small cell and non-small cell lung cancer are also provided using small organic compounds, siRNAs and blocking antibodies that inhibit or block the SHH / GLI pathway.

The invention provides compositions and methods for increasing hair growth and decreasing hair loss. In one embodiment, the compositions comprise a plurality of hair growth agents. Optionally, the hair growth agents are selected from the group consisting of: IGF-1, FGF-2, FGF-10, PDGF-AA, Wnt-3a, noggin, ephrin-A3, sonic hedgehog (SHH), BMP-6 and hypoxanthine.

The invention relates to a method for inducing a human pluripotent stem cell to differentiate into an RPE cell. According to the method, an inhibitor is used for inducing the human pluripotent stem cell to differentiate into a neural precursor; after Shh, IGF1 and EGF growth factors are utilized to activate ERK 1 / 2, JNK, Sonic hedgehog signal routes, the cell is presented as the shape of neuroepithelium, Activen A and Chir99021 are added to activate TGFbeta and Wnt signal routes respectively to induce a neuro-epithelial cell into a retinal progenitor cell; adherent culture is conducted on theretinal progenitor cell to obtain an RPE cell at an underdeveloped state. The invention further studies the field of applying the underdeveloped RPE cell to treating retinal degenerative diseases. Compared with the prior art, the method firstly makes three stages of differentiating the human pluripotent stem cell to the underdeveloped RPE cell and related small molecular substances and growth factors used therein clear. Compared with a matured RPE, the underdeveloped RPE obtained through differentiation can treat the retinal degenerative diseases more effectively after being transplanted.

Methods and compositions for increasing trichogenicity of cells in culture are provided. One embodiment provides culturing dissociated mammalian dermal cells in vitro in the presence of an effective amount of one or more sonic hedgehog (Shh) pathway agonists to increase the trichogenicity of the dissociated mammalian dermal cells compared to untreated dissociated mammalian dermal cells. The cell culture optionally includes epidermal cells. Preferred Shh agonists include, but are not limited to CUR-0236715 and CUR-0201365 available from Curis, Inc. Trichogenicity is measured using the Aderans Hair Patch Assay™. The cultured dermal cells can be maintained in culture in the presence of the one or more Shh agonists for at least 1 to 7 or more days prior to harvest. The treated, cultured dermal cells can be used to treat hair loss in a mammalian subject, preferably a human, by implanting them in an effective amount to induce hair follicle formation.

The invention provides metastatic tumor deletion protein small-molecule cyclopeptide, derivatives or salts thereof, a preparation method for the metastatic tumor deletion protein small-molecule cyclopeptide, the derivatives or salts thereof and an application of the metastatic tumor deletion protein small-molecule cyclopeptide, the derivatives or salts thereof in preparation of antitumor medicaments. The metastatic tumor deletion protein small-molecule cyclopeptide is low in molecular weight, high in stability and very low in toxicity and can enter cells through cell membranes to inhibit endocytosis of tumor cells and interfere morphologic change of the cell membranes and conduction of relevant antitumor signals by inhibiting dimerization of Mtss1 protein, so that cell proliferation and growth caused by tumor stimulating factors such as epidermal growth factors EGF, platelet derived growth factor PDGF or sonic hedgehog (shh) factors are weakened, wherein the in-vitro inhibition activity of nanomole-scale inhibitor-protein can remarkably inhibit the endocytosis of the cells after the inhibitor-protein is directly added into cell culture fluid without being transfected or packaged by lipidosome.

The invention discloses a nerve regeneration gel as well as a preparation method and application thereof. The matrix of the nerve regeneration gel is formed by fibrinogen, thrombin, laminin and fibronectin; the nerve regeneration gel contains procyanidine, sonic hedgehog, an epidermal growth factor, neurenergen-3 and a vascular endothelial growth factor. In-vitro test and animal test show that thegel is capable of accelerating neuron regeneration and neurite extension and repairing the injured nerve tissue. The matrix of the gel comprises fibrin, laminin and fibronectin and is capable of reducing formation of cavities and accelerating adhesion and proliferation of endogenous neural stem cells; the procyanidine in the gel is capable of resisting oxidation and inhibiting inflammation; the sonic hedgehog, the epidermal growth factor and the neurenergen-3 are capable of accelerating proliferation of the stem cells and differentiation to neurons of the stem cells; the vascular endothelialgrowth factor is capable of accelerating generation of blood vessels. The gel can be formed in situ on injured parts and can be used for treating nervous system injury.

Dopamine-producing neural precursor cells are produced by: producing a cell population containing Corin and / or Lrtm1 positive cells via steps (1) and (2) as will be shown below; collecting the Corin and / or Lrtm1 positive cells from the cell population thus obtained by using a substance that binds to Corin and / or a substance that binds to Lrtm1; and suspension-culturing the Corin and / or Lrtm1 positive cells in a liquid culture medium that contains one or more neurotrophic factors: (1) a step for adhesion-culturing pluripotent stem cells in the absence of any feeder cells in an undifferentiatedstate-maintaining culture medium that contains a sonic hedgehog (SHH) signal stimulant and an undifferentiated state-maintaining factor in the presence of an extracellular matrix; and (2) a step for culturing the cell population obtained in step (1) in a liquid culture medium that contains one or more differentiation inducing factors.

The invention belongs to the field of pharmacy, and relates to an application of a TCM monomer of apigenin to prepare a medicine for treating the pancreatic cancer. A CCK-8 method for evaluation, repeated screening and optimization, and a pharmacodynamic test for inhibiting proliferation of pancreatic cancer SW1990 cells are adopted to screen an effective monomer, having a strong anti-tumor effect, of apigenin. Moreover, an equipment of apigenin for interfering a Sonic Hedgehog signal channel of human pancreatic cancer SW1990 stem cells is carried out. The result shows that apigenin can obviously inhibit proliferation of pancreatic cancer stem cells, lower the ratio of pancreatic cancer stem cells, and reduce self-renewable ability of pancreatic cancer stem cells. The ratio of CD24+CD44+ cells is obviously lowered through flow cytometry; the amount of cancer stem cells cultured free of serum decreases; and expression of members in the Sonic Hedgehog signal channel at mRNA and protein levels is obviously lowered. The TCM monomer of apigenin can be taken as an individual unique active component for preparing the medicine for treating the pancreatic cancer.

Methods are provided in which a sterol-depleting agent such as β-cyclodextrin (βCD), is used to modulate signaling by a differentiation signaling protein such as Hedgehog protein or a BMP in vitro. As illustrated herein, the use of βCD in conjunction with Sonic Hedgehog N-terminal peptide (ShhN) causes substantially all of the cells in neural plate explants to differentiate as neurons, such as motor neurons. Also provided are cell therapy methods and screening methods that rely on the modulation of signaling of a differentiation signaling protein such as Hedgehog, by a sterol-depleting agent such as βCD.

The invention relates to a spinal cord OLIG2<+> nerve progenitor cell induction and self-renewal culture system, an induction method and application. The culture system comprises a basic culture medium, an induced differentiation factor and an in-vitro maintenance factor, wherein the induced differentiation factor and the in-vitro maintenance factor are combined with the basic culture medium for use; the induced differentiation factor at least comprises a 0.01-50 microns of GSK3 inhibitor, a 0.01-500 microns of TGF beta inhibitor and a 0.01-500 microns of BMP inhibitor; and the in-vitro maintenance factor comprises a 0.01-50 microns of GSK3 inhibitor, a 0.01-500 microns of TGF beta inhibitor, 0.01-5000 ng / mL of Sonic Hedgehog, a 0.01-20 microns of Smoothened agonist, a 0.01-500ng / mL of LEGF family growth factor, a 0.01-500 ng / mL of FGF family growth factor, a 0.01-500 microns of BMP inhibitor, a 0.01-50 microns of JAK1 / 2 inhibitor, a 0.01-10000nM of Src kinase inhibitor and a 0.01-50 microns of RetinoicAcid.

Methods of generating spinal cord glutamatergic interneurons (V2a interneurons) from human pluripotent stem cells (hPSCs) are provided. A method of the present disclosure may include culturing a first population of hPSCs in vitro in a neural induction medium that includes: a retinoic acid signaling pathway activator; a sonic hedgehog (Shh) signaling pathway activator; and a Notch signaling pathway inhibitor, wherein the culturing results in generation of a second population of cultured cells containing CHX10+ V2a interneurons. Also provided are non-human animal models that include the hPSC-derived spinal cord glutamatergic interneurons, and methods of producing the non-human animal models.

The invention provides methods for the diagnosis and treatment of musculoskeletal disorders relating to the Hedgehog pathway, including but not limited to muscular dystrophy (e.g., Duchenne Muscular Dystrophy) using agents that agonize Sonic Hedgehog (shh), and thereby, the Hedgehog signaling pathway. Said agonizing agents include, e.g., the compounds of the invention (e.g., a compound of Formula I). The invention also provides methods of screening for agents that are capable of increases the proliferation of muscle and / or muscle precursor cells.

The invention provides a nutrient medium composition and associated methods for lengthening the useful life of a culture of muscle cells. Disclosed is a method of culturing mammalian muscle cells, including preparing one or more carriers coated with a covalently bonded monolayer of trimethoxy-silylpropyl-diethylenetriamine (DETA); verifying DETA monolayer formation by one or more associated optical parameters; suspending isolated fetal rat skeletal muscle cells in serum-free medium according to medium composition 1; plating the suspended cells onto the prepared carriers at a predetermined density; leaving the carriers undisturbed for cells to adhere to the DETA monolayer; covering the carriers with a mixture of medium 1 and medium 2; and incubating. A cell nutrient medium composition includes Neurobasal, an antibiotic-antimycotic composition, cholesterol, human TNF-alpha, PDGF BB, vasoactive intestinal peptides, insulin-like growth factor 1, NAP, r-Apolipoprotein E2, purified mouse Laminin, beta amyloid, human tenascin-C protein, rr-Sonic hedgehog Shh N-terminal, and rr-Agrin C terminal.

The present invention relates to a method for preparing induced dopaminergic neuronal progenitors (iDPs) comprising inducing an expression of Oct4, Sox2, Klf4, and c-Myc genes in adult cells and direct reprogramming of the adult cells to the iDPs by treating the cells with sonic hedgehog (SHH) and fibroblast growth factor 8 (FGF8); and a cell therapy product and a composition for treating or preventing Parkinson's Disease (PD) which comprises the iDPs as active ingredients. In addition to this, the present invention relates to a method for preparing midbrain dopaminergic neurons comprising isolating NSC-like colony by culturing the iDPs, dissociating the isolated NSC-like colony, and culturing the cells on the neural cell differentiation medium. Further, the present invention relates to a method for treating PD or a method for screening medicine for preventing or treating PD using the cells of the present invention. The progenitors prepared by the method for preparing the iDPs of the present invention can be widely used in the known art since the neuronal progenitors have significantly higher efficiency in differentiating to the dopaminergic neurons compared to conventional methods and lack side effects such as immunogenicity and ethical issues because patients' own somatic cells can be used.

The present invention relates to compounds for modulating sonic hedgehog signaling and preventing or treating cancer.

The present invention generally relates to compositions, reagents and methods for detecting and treating a neural tube defect in a fetus. One aspect of the invention provides a method including administrating a composition containing noggin or LDN-193189 to the fetus in utero. In certain embodiments, the composition is administrated if the maternal blood or amniotic fluid contains an elevated amount of BMP4 and / or a reduced amount of noggin. In another aspect of the invention, the method includes administrating a composition containing GDC-0449 to the fetus in utero. In certain embodiments, the GDC-0449 is administrated if the maternal blood or amniotic fluid contains an elevated amount of sonic hedgehog.

The present invention relates to the field of stem cells. More specifically, the present invention provides methods and compositions useful for the highly efficient conversion of human stem cells to lineage-specific neurons. In a specific embodiment, a method of inducing differentiation of human stem cells into dopaminergic (DA) neurons comprises the steps of (a) transfecting human stem cells with a lentiviral vector encoding Atoh1, wherein the vector is Dox inducible; and (b) growing the transfected cells in culture in the presence of Dox, Sonic Hedgehog (SHH) and FGF-8b until DA neurons are induced.

Described herein are compositions and methods for the treatment of Parkinson's disease (PD) and / or to protect dopaminergic nigrostriatal neuronal cell bodies from 6-OHDA-induced neurotoxicity in a mammal. In various embodiments of the invention, the dopaminergic neuron differentiation factor sonic hedgehog (Shh) and / or its downstream transcription factor target Gli-1 are used in connection with gene therapeutic techniques or direct peptide injection for the aforementioned indications. Kits useful in practicing the inventive method are also disclosed, as are animal models useful for studying various neurodegenerative conditions.

The present invention relates to compounds, small interfering RNAs and compositions and methods of inhibiting tumorigenesis using agents that inhibit the sonic hedgehog and GLI signaling pathway, including agents that inhibit GLI expression, synthesis and / or function. The present invention also relates to particular biomarkers that can be used in the diagnosis and prognosis of cancer. Methods of treating cancer, including glioblastomas, medulloblastomas, basal cell carcinomas, prostate cancer and small cell and non-small cell lung cancer are also provided using small organic compounds, siRNAs and blocking antibodies that inhibit or block the SHH / GLI pathway.

Described herein are compositions and methods for the treatment of Parkinson's disease (PD) and / or to protect dopaminergic nigrostriatal neuronal cell bodies from 6-OHDA-induced neurotoxicity in a mammal. In various embodiments of the invention, the dopaminergic neuron differentiation factor sonic hedgehog (Shh) and / or its downstream transcription factor target Gli-1 are used in connection with gene therapeutic techniques or direct peptide injection for the aforementioned indications. Kits useful in practicing the inventive method are also disclosed, as are animal models useful for studying various neurodegenerative conditions.

The invention relates to the technical field of stem cell culture, in particular to cell culture fluid, application of the cell culture fluid and a method of inducting DPSCs (Dental Pulp Stem Cells) to differentiate into neuron-like cells. The cell culture fluid provided by the invention comprises basic culture fluid, GDNFs (Glial Cell-Derived Neurotrophic Factors), Shh (Sonic hedgehog), EGFs (Epidermal Growth Factors) and cAMP (Cyclic Adenosine monophosphate). The culture fluid provided by the invention can be used for inducting the DPSCs to differentiate into the neuron-like cells. When the culture fluid is used for inducing the DPSCs, the form of the DPSCs starts to change from 12h; after the 24h from the induction, the form of the DPSCs is obviously changed; the cell refractivity starts to be enhanced; cell processes increase and grows and differentiate into the form of the neuron-like cells. Through western bolt detection, after 24h from the induction, the expression amounts of Nestin and MAP2 (Microtubule-Associated Protein 2) in the DPSCs are obviously increased. Therefore the culture fluid has the advantages of short period and high efficiency when being used for inducing the DPSCs to differentiate into the neuron-like cells.

The invention discloses a building method and use of an antineoplastic compound screening model, which can realize high flux screening of an antineoplastic compound for reversion of zebra fish Sonic Hedgehog (Shh) signal path overexpression and is identified by the degree of body axis bending toward the back side, belongs to technical innovation in the technical field of medicine. The antineoplastic compound screening model can be used for preliminary rapid screening of a tumor-inhibition lead compound with latent specificity. A zebra fish tulp3 gene is used as a target gene, and the tulp3 gene is partially silenced by a specific Morpholino oligonucleotide sequence so that Shh path overexpression is realized. When the Shh path is over-expressed, zebra fish shows of body axis specific-bending toward the back side, and the above phenotype is used for identifying Shh path overexpression. Through observation of the zebra fish body appearance, the Shh path overexpression case is directly known. Compared with a cell model, the antineoplastic compound screening model is visual and convenient and is conducive to high flux screening of drugs utilizing Shh path as a target point.

Treating Sonic Hedgehog-Associated Medulloblastoma comprises inhibiting the synthesis or biologic activity of leukotrienes that drive Nestin expression in cancerous or precancerous granule neuron precursors and that further drive growth and proliferation of medulloblastoma cells through Nestin-mediated aberrant Sonic Hedgehog signaling.

The invention provides methods for the diagnosis and treatment of musculoskeletal disorders relating to the Hedgehog pathway, including but not limited to muscular dystrophy (e.g., Duchenne Muscular Dystrophy) using agents that agonize Sonic Hedgehog (shh), and thereby, the Hedgehog signaling pathway. Said agonizing agents include, e.g., the compounds of the invention (e.g., a compound of Formula I). The invention also provides methods of screening for agents that are capable of increasing the proliferation of muscle and / or muscle precursor cells.

The present invention relates to treatment methods and methods for sustained delivery of one or more exogenous factors to desired nervous system sites. In certain embodiments, the invention relates to the use of biodegradable microspheres to deliver exogenous factors, such as the morphogenic factor, sonic hedgehog (Shh), to the site of spinal cord injury. In certain embodiments, the Shh-releasing microspheres are administered together with stem cells, which may be spinal cord neural stem cells. In certain embodiments, the invention relates to regrowth of neural cells in both the central and peripheral nervous systems.

The present invention relates to compounds for modulating sonic hedgehog signaling and preventing or treating cancer.

Described herein are compositions and methods for the treatment of Parkinson's disease (PD) and / or to protect dopaminergic nigrostriatal neuronal cell bodies from 6-OHDA-induced neurotoxicity in a mammal. In various embodiments of the invention, the dopaminergic neuron differentiation factor sonic hedgehog (Shh) and / or its downstream transcription factor target Gli-1 are used in connection with gene therapeutic techniques or direct peptide injection for the aforementioned indications. Kits useful in practicing the inventive method are also disclosed, as are animal models useful for studying various neurodegenerative conditions.