30 results about "Neuroectoderm" patented technology

The present invention is, generally, directed to the use of betulinic acid and derivatives thereof for the treatment of neuroectodermal tumors. The present invention is based on the discovery that betulinic acid and its derivatives are potent anti-neuroectodermal agents. As disclosed herein, betulinic acid and its derivatives are useful for the treatment of neuroectodermal tumors, including, due to its distinct mechanism of action, neuroectodermal tumors that are resistant to conventional chemotherapeutical agents. In addition to the new use of known compounds, the invention discloses novel compounds and pharmaceutical compositions for the treatment of neuroectodermal tumors.

The invention provides for the production of several humanized murine antibodies specific for the antigen LK26, which is recognized by the murine antibody LK26. This antigen is expressed in all choriocarcinoma, teratocarcinoma and renal cancer cell lines whereas it is not expressed on cell lines of leukaemias, lymphomas, neuroectodermally-derived and epithelial tumour cell lines (excepting a small subset of epithelial cell lines). Furthermore, whereas renal cancer cell lines express the LK26 antigen, normal renal epithelial cells do not. Similarly, with the exception of the trophoblast, all normal adult and fetal tissues tested are negative for the LK26 phenotype. The invention also provides for numerous polynucleotide encoding humanized LK26 specific antibodies, expression vectors for producing humanized LK26 specific antibodies, and host cells for the recombinant production of the humanized antibodies. The invention also provides methods for detecting cancerous cells (in vitro and in vivo) using humanized LK26 specific antibodies. Additionally, the invention provides methods of treating cancer using LK26 specific antibodies.

The present invention is directed to methods and compositions for the treatment and diagnosis of neuroectodermally-derived tumors, such as gliomas. The inventive methods of treatment generally include local (e.g., intracavitary) administration of a chloroxotoxin moiety conjugated to a cytotoxic moiety to a patient. Also provided are diagnostic methods for screening neoplastic neuroectodermal tumors.

The present invention is directed to compositions and methods for the treatment of retinoblastoma and neuroectodermal derived tumors, such as primitive neuroectodermal tumors (PNET) and neuroblastoma. In particular, the present invention is directed to the use of 4F-benzoyl-TN14003 peptide or analogs or derivatives thereof for treating neuroblastoma and retinoblastoma.

Assays and kits for detecting aberrant cells of neuroectodermal origin in a body fluid of an individual, comprising testing for expression of GLAST1b as a biomarker of the cells are disclosed. Intact GLAST1b and/or fragments thereof may be detected in the fluid. Alternatively, another analyte indicative of the expression of GLAST1b by the cells may be detected. The assay is particularly suitable for detecting expression of aberrant neuronal populations such as resulting from brain hypoxia. The fluid can be cerebrospinal fluid (CSF).

The invention provides conjugates, comprising an organ, tissue or tumor cell homing molecule linked to a moiety. Such a moiety can be, for example, an oligonucleotide, small interfering RNA, gene, virus, protein, pharmaceutical or detectable agent. In addition the invention provides methods to diagnose or treat neuronal or neuromuscular disease, or a pathology of the brain, or a tumor of neuronal or neuroectodermal origin, by administrating to a subject having or suspected of having a pathology a molecule or conjugate that homes to, binds to and is taken up by the brain cells or neuronal cells, or by the tumor cells of neuronal or neuroectodermal origin. The invention also provides a method of identifying and measuring neurite growth in neuronal cells.

Specific drug delivery to tumor cells without affecting normal cells is a major challenge in cancer treatment. The present invention incorporates embedding nonionic surfactant vesicles (niosomes) containing an anti-cancer therapeutic agent with chlorotoxin into a thermosensitive chitosan hydrogel network. Chitosan has mucoadhesive property which can be used in the targeting of the tumor cells with the mucin over expression. Chlorotoxin is a 36 amino acid peptide obtained from Leiurus quinquestriatus scorpion venom which binds preferentially to tumor cells of neuroectodermal origin but not to normal cells. The incorporation of chlorotoxin along with niosomes in the chitosan hydrogel is used as the second targeting strategy to further improve the specific delivery of drugs to tumor cells such as glioma.

The invention discloses a method for preparing neural stem cells, which comprises a step of inductively culturing P19 cells in N2B27 culture medium to obtain a cell group containing neural stem cells above 94%. The method can culture the P19 cells in an environment without blood serum and retinoic acid, thus suppressing the interference of the blood serum with complex components and preventing the obtained neural stem cells from being transformed posteriorly by retinoic acid. Moreover, the method can directly transform pluripotent stem cells to neutral stem cells without resulting in selective cell apoptosis. The neutral stem cells obtained by the invention have anterior neutral plate characteristics and totipotency, and can well simulate the neurogenesis process in body. Accordingly, the neural stem cells can be used as the research model for analyzing neural induction and neural differentiation process from epiblast to neuroderm, thus providing an ideal path for researching development of embryo after nidation.

Pluripotent human embryonic stem cells (hESCs) hold great potential for restoring tissue and organ function, which has been hindered by inefficiency and instability of generating desired cell types through multi-lineage differentiation. This instant invention is based on the discovery that pluripotent hESCs maintained under defined culture conditions can be uniformly converted into a specific lineage by small molecule induction. Retinoic acid induces specification of neuroectoderm direct from the pluripotent state of hESCs and triggers progression to neuronal progenitors and neurons efficiently. Similarly, nicotinamide induces specification of cardiomesoderm direct from the pluripotent state of hESCs and triggers progression to cardiac precursors and cardiomyocytes efficiently. This technology provides a large supply of clinically-suitable human neuronal or cardiac therapeutic products for CNS or myocardium repair. This invention enables well-controlled efficient induction of pluripotent hESCs exclusively to a specific clinically-relevant lineage for tissue and organ engineering and regeneration, cell-based therapy, and drug discovery.

This invention relates to the production of populations of Smooth Muscle Cells (SMCs) of specific embryonic lineages, such as neuroectodermal and mesodermal SMCs. Pluripotent stem cells are cultured in one or more lineage induction media to produce progenitor cells of a defined embryonic lineage, which are then cultured in an SMC induction medium to produce a population of SMCs of the embryonic lineage. Populations of SMCs of defined lineages may be useful, for example, in in accurately modelling vascular disease.

Methods for differentiating human pluripotent stem cells to dorsal neuroectoderm progenitors and further to glial progenitor cells and oligodendrocyte progenitor cells (OPCs) using inhibitors of BMP signaling and MAPK/ERK signaling are provided. Also provided are cells and cellular compositions obtained by such methods, and uses of such cells. Further provided are methods and protocols for efficiently differentiating human pluripotent stem cells to OPCs in the absence of the ventralizing morphogen SHH or a SHH signaling activator. The methods of the present disclosure reproducibly produce dorsal neuroectoderm progenitor cells by day 7 of the differentiation process, glial progenitor cells by day 21 of the differentiation process and OPCs by day 42 of the differentiation process.

A transcription factor both necessary and sufficient for human neuroectoderm specification, Pax6, as well as applications thereof, is disclosed.

The presently disclosed subject matter provides for in vitro methods of inducing differentiation of human stem cells into neural crest, cranial placode or non-neuro ectoderm precursors, and cells generated by such methods. The presently disclosed subject matter also provides for uses of such cells for treating neurodegenerative and pituitary disorders.

A method for producing a brain organoid is provided, including a step of culturing a neuroectoderm marker-positive cell aggregate in a medium containing an extracellular matrix with a concentration of more than 10% by volume.

Methods for differentiating pluripotent stem cells to neuroectoderm in dynamic suspension culture using small molecule or protein inhibitors of TGF[beta]/Activin/Nodal signaling and BMP signaling are provided. Also provided are method and protocols for differentiating pluripotent stem cells such as human embryonic stem cells first to neuroectoderm, then further to glial progenitor cells, and further to oligodendrocyte progenitor cells (OPCs), and compositions obtained thereby. The methods of the present disclosure reproducibly produce neuroectoderm progenitor cells by day 7 of the differentiation process, glial progenitor cells by day 21 of the differentiation process and OPCs by day 42 of the differentiation process.

The invention provides application of KDM6 as a target in preparation of a medicine for improving early-stage neuroectoderm differentiation efficiency. According to the application, the deletion of demethylase KDM6 of H3K27me3 can promote the improvement of the differentiation efficiency of human embryonic stem cells to the early neuroectoderm; and meanwhile, the research finds that the differentiation efficiency can also be improved by using a KDM6 small-molecule inhibitor (GSK-J1) in the early neuroectoderm differentiation process. Therefore, a KDM6A knockout reagent, a KDM6B knockout reagent and a KDM6 inhibitor can promote early generation of neurons by improving early neural differentiation efficiency and improve neuron apoptosis (not improving existing neuron metabolism), and are potential novel drugs for neurodegenerative diseases.