116 results about "Pancreatic A Cells" patented technology

It is intended to provide a method of forming pancreatic β cells from mesenchymal cells characterized by comprising using mammal-origin mesenchymal cells as starting cells, culturing these cells in the presence of, for example, a pancreatic β cell-forming agent, and selecting and separating the thus obtained pancreatic βcells with the use of a gene expressed specifically in such cells as a selection marker; a remedy for glucose intolerance which comprises pancreatic β cells obtained by the above method as the active ingredient; a pancreatic β cell-forming agent such as a cytokine to be used in the above method; a method of screening a candidate compound promoting the formation of pancreatic β cells from mesenchymal cells; and a pancreatic β cell formation promoter obtained by this screening method.

A method of converting differentiated non-hormone producing pancreatic cells into differentiated hormone producing cells is disclosed. The method comprises two steps: first, culturing cells under conditions which convert differentiated non-hormone producing cells into stem cells; and second, culturing stem cells under conditions which provide for differentiating stem cells into hormone-producing cells. The invention defines growth and differentiation factors that are presented to the stem cells to result in their differentiation into hormone-producing cells, especially insulin-producing cells. The invention provides a new source of large quantities of hormone producing cells such as insulin-producing cells that are riot currently available for therapeutic uses such as the treatment of diabetes.

The present invention generally relates to methods and compositions to generate a secondary iPS (2iPS) cell to produce somatic cells of a rare differentiation cell type fate. In some embodiments, the method relates to an increase in efficiency of differentiation and production of high yields of somatic cells of a rare differentiation cell type fate produced from secondary iPS (2iPS) cells as compared to their differentiation from other pluripotent stem cell sources such as ES cells or primary iPS cells. In some embodiments, the present invention relates to compositions, methods and systems for reprogramming a first somatic cell into a primary iPS cell, where the primary iPS cell is then differentiated along a selected linage to produce a second somatic cell, which is then reprogrammed to a secondary iPS cell (2iPS) cell. The 2iPS cell has a high efficiency of differentiating into a cell of the same cell type as the second somatic cell, e.g., a somatic cells of a rare differentiation cell type fate such as but not limited to a ventricular cardiomyocyte, a pancreatic β-cell or a hepatic cell. In some embodiments, the first somatic cell is a fibroblast, or a cardiac cell, but is not limited to cardiac fibroblast cells. In some embodiments, the present invention relates to compositions, methods and systems to produce ventricular cardiomyocytes from secondary induced pluripotent stem cells (iPSC), where the iPSC are themselves generated from ventricular cardiomyocytes. The secondary iPS (2iPS) cell generated from ventricular cardiomyocytes have a higher cardiomyogenic potential and high cardiomyogenic yield as compared to primary iPSC, and are useful in drug discovery, disease modeling and cell-based therapy.

The invention relates to the discovery that the proliferation and survival of pancreatic progenitor cells can be enhanced by contacting the cells with, (1) a caspase inhibitor sufficient to reduce apoptosis in the pancreatic endocrine cells; and, (2) a growth factor in an amount sufficient to increase the level of activated Akt in the pancreatic endocrine cells.

The present invention relates to one or more SGLT2 inhibitors or pharmaceutically acceptable forms thereof for use in the treatment and / or prevention of a metabolic disorder in a feline animal, preferably wherein the metabolic disorder is one or more selected from the group consisting of: ketoacidosis, pre-diabetes, diabetes mellitus type 1 or type 2, insulin resistance, obesity, hyperglycemia, impaired glucose tolerance, hyperinsulinemia, dyslipidemia, dysadipokinemia, subclinical inflammation, systemic inflammation, low grade systemic inflammation, hepatic lipidosis, atherosclerosis, inflammation of the pancreas, neuropathy and / or Syndrome X (metabolic syndrome) and / or loss of pancreatic beta cell function and / or wherein the remission of the metabolic disorder, preferably diabetic remission, is achieved and / or maintained.

The present invention relates to novel heterocyclic compounds of the general formula (I), their derivatives, analogs, tautomeric forms, stereoisomers, polymorphs, hydrates, solvates, pharmaceutically acceptable salts and compositions, metabolites and prodrugs thereof. The present invention more particularly provides novel hetereocycles of the general formula (I). Also included is a method of treatment of immunological diseases, inflammation, pain disorder, rheumatoid arthritis; osteoporosis; multiple myeloma; uveititis; acute and chronic myelogenous leukemia; ischemic heart disease; atherosclerosis; cancer; ischemic-induced cell damage; pancreatic beta cell destruction; osteoarthritis; rheumatoid spondylitis; gouty arthritis; inflammatory bowel disease; adult respiratory distress syndrome (ARDS); psoriasis; Crohn's disease; allergic rhinitis; ulcerative colitis; anaphylaxis; contact dermatitis; muscle degeneration; cachexia; asthma; bone resorption diseases; ischemia reperfusion injury; brain trauma; multiple sclerosis; sepsis; septic shock; toxic shock syndrome; fever, and myalgias due to infection in a mammal comprising administering an effective amount of a compound of formula (I) as described above.

The present invention is directed to the identification of a biomarker specifically located in the plasma membrane of pancreatic beta cells. It was selected by a Systems Biology approach on Massively Parallel Signal Sequencing datasets obtained in human islets and Affymetrix microarray datasets on human islets, purified rat primary beta and non beta cells and insulinoma cells. Based on a set of specific features the biomarker is a unique candidate for imaging and targeting strategies to study the pancreatic beta cell mass in health and disease (T1 D, T2D, pancreatic cancers, obesity, islet transplantation, beta cell regeneration). The five specific features of the selected biomarkers are: 1) Preferentially expressed in pancreatic islets as compared to surrounding tissues; 2) Higher expression in pancreatic beta cells than in pancreatic alpha cells or than in other islet non-beta cells; 3) Expression levels in pancreatic beta cells are higher or comparable to glucokinase which is an enzyme specifically expressed in the pancreatic beta cell; 4) Located in the membrane and as such targetable with antibodies, peptides or small molecules which allows imaging, targeting and immunohistochemistry; and 5) Expression is not induced during the process of inflammation of the beta cell mass and the protein is not enriched in T-cells and dendritic cells or in other cells participating in the inflammation process.

The invention provides a pancreatic-like structure and a construction method thereof. The construction method comprises the following steps: A, inducing stem cells and / or progenitor cells in vitro todifferentiate into pancreatic-like cell clusters; B, mixing the vascularized cells, the pancreatic-like cell clusters and a hydrogel material, and performing biological printing to obtain a pre-gel three-dimensional structure body; and C, culturing the pre-gel three-dimensional structure body by adopting a multi-cell culture solution and / or a bioreactor to obtain the pancreas-like structure body.The pancreatic-like structure provided by the invention is composed of vascularized cells and pancreatic-like tissue cells, and has the form, phenotypic characteristics and physiological functions ofnatural tissues. The method can be applied to the aspects of organoid construction, tissue / organ / human body chips, tissue engineering, regenerative medicine, in-vitro physiological model / pathologicalmodel / pharmacological model construction, cytobiology or drug research and the like.

The invention discloses a method for inducing directional differentiation of human induced pluripotent stem cells into pancreatic cells. The invention provides an application of a substance for inhibiting LSD1 gene expression in inducing the directional differentiation of stem cells into endoderm cells or an application of the substance for inhibiting LSD1 gene expression in inducing the directional differentiation of the stem cells into the pancreatic cells. Experiments prove that an LSD1 inhibitor or shRNA is to be adopted in the study to inhibit or silence the LSD1 expression level in hiPSCs at different degrees, the shRNA is screened out so that the transformation of the hiPSCs from proliferation into entoderm differentiation can be better promoted to prepare for promoting the further uniform differentiation state of the hiPSCs; and next, an established four-step induced differentiation system is adopted to induce efficient directional differentiation into IPCs. The theoretical basis is laid for optimizing or establishing an efficient and directional differentiation scheme for the hiPSCs to the IPCs.

The present invention provides a method of more efficiently producing pancreas cells, particularly pancreatic hormone-producing cells, a method of stably producing pancreas cells in a large amount by more efficiently inducing differentiation of stem cells into pancreas cells, a medicament containing a pancreas cells and a screening method using the cells.A method of producing pancreatic hormone-producing cells, including subjecting stem cells to the following steps (1)-(4):(1) a step of cultivating stem cells in a medium containing an activator of activin receptor-like kinase-4,7 and a GSK3 inhibitor(2) a step of cultivating the cells obtained in the aforementioned step (1) in a medium containing an activator of activin receptor-like kinase-4,7(3) a step of cultivating the cells obtained in the aforementioned step (2) in a medium containing any one or more kinds selected from the group consisting of (a) retinoic acid receptor agonists, (b) at least one kind selected from the group consisting of inhibitors of AMP-activated protein kinase and / or activin receptor-like kinase-2,3,6, and BMP antagonists, and (c) inhibitors of activin receptor-like kinase-4,5,7(4) a step of cultivating the cells obtained in the aforementioned step (3).

A biomarker for pancreatic beta-cell mass comprising measuring the levels of CFC1 in the serum of a subject is described. The biomarker provides a noninvasive means for measuring pancreatic beta cell mass that is particularly useful for monitoring the efficacy of treatments for metabolic disorders such as Type I or Type II diabetes, including pancreatic islet cell transplantations.

The present invention provides various methods for increasing beta cell mass. In certain embodiments, such methods include steps of administering to a subject an effective amount of: (a) SDF1, a polypeptide having amino acid sequence substantially homologous thereto, or a fragment thereof capable of increasing beta cell survival; and (b) GLP-1 Exendin-4, a polypeptide having amino acid sequence substantially homologous to GLP-1 or Exendin-4, or a fragment of GLP-1 or Exendin-4 capable of promoting beta cell proliferation, whereby beta cell mass is increased in the subject.

The invention provides a method for generating a type II diabetes mellitus and / or Syndrome X model in pigs. A method of the invention comprises partially destructing pancreatic beta-cells in pigs. From these pigs, a pig is preferably selected that comprises a fasting plasma glucose level higher than 6 mmol / L. The invention further provides a pig according to the invention and uses thereof.

The invention provides stem cell derived beta-pancreatic cells and animal models of T2D in which cells have been grafted. The stem cells bear a mutated form of SLC30A8 conferring protection or susceptibility to T2D. The cells and animal models can be used for drug screening as well as to provide insights into the mechanism of T2D and potentially new therapeutic and diagnostic targets.

The present invention relates to methods and compositions for inhibiting proliferation and inducing cell death in a population of cancer cells by (i) increasing the amount of the differentiation associated protein MDA-7, and (ii) decreasing RAS activity within the population. It is based, at least in part, on the discovery that decreasing expression of a mutated, activated K-ras gene, together with introducing an expressible mda-7 gene, in pancreatic cells had a synergistic growth-inhibitory and anti-survival effect, and abolished tumorigenicity of the cells in athymic nude mice. The methods of the invention may be directed to the therapy of pancreatic cancer and other malignancies.

Methods are provided for the establishment and maintenance in long term culture of hormone secreting cells. Cells are derived from tumorous or non-tumorous animal or human tissues, including ovary, endometrium, trophoblast, pituitary, thyroid, and pancreas. The cells secrete into the culture medium hormones such as estrogens, progestins, follicle-stimulating hormone, luteinizing hormone, human chorionic gonadotrophin, thyroxin, glucagon, and insulin, depending on the tissue of origin of individual cell cultures. Contact with an appropriate secretogogue causes the cells to respond with increased hormone secretion. For instance, ovarian follicular cells respond to follicle-stimulating hormone with increased estrogen and progesterone secretion. Pancreatic cells respond to elevated glucose with increased insulin secretion. The cells proliferate in in vitro for up to one year or longer, during which time they retain their hormone-secretion profile. The cells may be frozen for storage, and retain their hormone-secretion profile after thawing. The cell cultures are useful for the production of human hormones, for the bio-assay of drugs such as therapeutic gonadotrophin, for the testing of drug efficacy and design, and for toxicity testing of drugs and chemicals. The cells may also be implanted in an individual to replace deficient hormone secretion. For instance, insulin secreting pancreatic cells may be implanted in a diabetic individual as an adjunct or replacement therapy for exogenously administered insulin.

This invention relates to the in vitro differentiation of pluripotent cells into pancreatic progenitors by i) culturing pluripotent cells in a definitive endoderm (DE) medium comprising a TGFp ligand, fibroblast growth factor ( FGF), bone morphogenetic protein (BMP), a PI3K inhibitor and optionally a GSK3 β inhibitor to produce a population of definitive endoderm cells, ii) culturing the definitive endoderm cells in a first pancreatic medium comprising an activin antagonist; FGF; retinoic acid; and a BMP inhibitor to produce a population of dorsal foregut cells; iii) culturing the dorsal foregut cells in a second pancreatic medium comprising FGF, retinoic acid, a BMP inhibitor, and a hedgehog signalling inhibitor, and; iv) culturing the endoderm cells in a third pancreatic medium comprising FGF. The progenitor cells thus produced may be further differentiated into pancreatic endocrine cells. These methods may be useful, for example, in producing pancreatic cells for therapy or disease modelling.

It is discovered that sodium-channel blockers inhibit the secretion of glucagon from pancreatic alpha cells. The present disclosure, based on such discoveries, provides compositions and methods for the treatment of hyperglycemia and related diseases and conditions with Na-channel blockers.

The present invention relates to the use of a compound of formula (1): wherein: R1 comprises a carbonyl group and R2 is a hydrocarbyl group; optionally wherein said ring is further substituted; or a pharmaceutically acceptable salt thereof; in the manufacture of a medicament for use in one or more of: modulating the release of intracellular calcium from a store controlled by nicotinic acid adenine dinucleotide phosphate; modulating calcium spikes in mammalian cells; treating diseases in one or more of brain, heart, pancreatic cells (e.g. pancreatic acinar and pancreatic beta cells), immune cells, T-cells, haemopoietic cells including phagocytes; treating diseases in one or more of brain, heart, pancreatic cells (e.g. pancreatic acinar and pancreatic beta cells), immune cells, T-cells, haemopoietic cells including phagocytes by modulating the release of intracellular calcium from a store controlled by nicotinic acid adenine dinucleotide phosphate; treating diseases in one or more of brain, heart, and T-cells by modulating calcium spikes in mammalian cells.

The present invention relates to an in vitro or ex vivo method for producing a population of pancreatic beta-cells, comprising the step of inhibiting the expression or the activity of Arx in a population of pancreatic alpha-cells. The present invention also relates to method for inducing the conversion of pancreatic alpha-cells in pancreatic beta-cells in a patient in need thereof.

The invention provides a novel primary culture method of pancreatic duct epithelial cells of a rat. The method comprises the following steps of: a, separating a main pancreatic duct from a pancreatic tissue of a healthy rat; b, digesting and separating pancreatic tissue fragments by using mixed digestive enzyme by a step-by-step digestion method to obtain cell aggregates; and c, culturing and purifying the cell aggregates, namely rotating a vessel by using a time difference and jointly purifying by using a gradient serum culture medium to obtain the pancreatic duct epithelial cells. In the method, the raw material is taken from the common laboratory animal, namely the rat, and the main pancreatic duct can be quickly and efficiently stripped from the whole pancreatic tissue by using the tension of surrounding organs of the main pancreatic duct. The cell aggregates with a proper size can be obtained by the step-by-step digestion method; and the yield of the cultured cells can be improved by over 60 percent than that of the cultured cells by an overall digestion method. By combining three methods, namely, material taking, time difference-based vessel rotation and the use of the gradient serum culture medium, the pollution of other pancreatic cells is removed, and the epithelial cells are purified, wherein the purification rate of the epithelial cells of the invention can reach 95 percent.

This invention provides a polypeptide, TMEM27, and secreted forms thereof, nucleic acids and constructs encoding the same, and cells comprising the same. The TMEM27 protein is expressed in hormone positive cells at early stages of pancreas development and pancreatic ss-cells in the mature pancreas, whose expression promotes pancreatic ss-cell replication and increased islet mass. Applications of the protein in diagnostics and therapeutics are described.

Described herein are compounds having the following structure: formula (I) or a stereoisomer, pharmaceutically acceptable salt, oxide, or solvate thereof. Also disclosed are compositions containing the compounds, methods of inhibiting activity of DYRKl A in a cell, methods of increasing cell proliferation in a population of pancreatic beta cells, methods of treating a subject for a condition associated with insufficient insulin secretion, and methods of treating a subject for a neurological disorder.

The invention relates to a method for preparing differentiated pancreatic beta cells and application of the differentiated pancreatic beta cells. The method comprises the following steps: (1) performing three-dimensional suspension domestication culture on pluripotent stem cells; and (2) inducing the domesticated cells to differentiate into pancreatic beta cells. The invention further relates to a method for preparing a sodium alginate-polylysine-sodium alginate (APA) microencapsulated artificial pancreas islet from the differentiated pancreas beta cells. The method comprises the step of preparing the microencapsulated artificial pancreas islet by using a sodium alginate solution. The invention also relates to application of the pancreatic beta cells and the artificial pancreas islet.

The present invention relates to a method of increasing cell proliferation in a population of pancreatic beta cells and a method of treating a subject for a condition associated with an insufficient level of insulin secretion. Also disclosed is a composition. The composition includes a dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1 A) inhibitor and a transforming growth factor beta (TGFP) superfamily signaling pathway inhibitor.

The invention relates to a method of identifying, obtaining and / or quantifying a culture of pancreatic cells selected from the group consisting of ductal / endocrine progenitor cells, endocrine progenitor cells, early endocrine cells, and fully differentiated endocrine cells. Also contemplated is a method of expanding the numbers of such cells as well as sorting such cells. The invention further relates to a selective cell surface marker, DDR1, that permits the selection of a unique subset of cells with pancreatic endocrine progenitor phenotype. Furthermore, the invention relates to isolated cells selected from such cells and compositions thereof.