Reagents and methods for using human embryonic stem cells to evaluate toxicity of pharmaceutical compounds and other chemicals
First Claim
1. A method for identifying one or a plurality of cellular metabolites having a molecular weight of from about 10 to about 1500 Daltons that is differentially produced in human embryonic stem cells (hESCs) or human pluripotent stem cells contacted with a test compound from a population of secreted cellular metabolites, the method comprising the steps of:
- a) culturing hESCs or human pluripotent stem cells in the presence or absence of a test compound;
b) separating members of the population of cellular metabolites having a molecular weight of from about 10 to about 1500 Daltons that are secreted from hESCs or human pluripotent stem cells;
c) detecting one or a plurality of differentially produced cellular metabolites having a molecular weight of from about 10 to about 1500 Daltons from hESCs or human pluripotent stem cells; and
d) identifying at least one cellular metabolite having a molecular weight of from about 10 to about 1500 Daltons that is differentially produced in cells cultured in the presence of the test compound.
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Accused Products
Abstract
The invention provides biomarker profiles of cellular metabolites and methods for screening chemical compounds including pharmaceutical agents, lead and candidate drug compounds and other chemicals using human embryonic stem cells (hESC) or lineage-specific cells produced therefrom. The inventive methods are useful for testing toxicity, particularly developmental toxicity and detecting teratogenic effects of such chemical compounds.
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Citations
48 Claims
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1. A method for identifying one or a plurality of cellular metabolites having a molecular weight of from about 10 to about 1500 Daltons that is differentially produced in human embryonic stem cells (hESCs) or human pluripotent stem cells contacted with a test compound from a population of secreted cellular metabolites, the method comprising the steps of:
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a) culturing hESCs or human pluripotent stem cells in the presence or absence of a test compound; b) separating members of the population of cellular metabolites having a molecular weight of from about 10 to about 1500 Daltons that are secreted from hESCs or human pluripotent stem cells; c) detecting one or a plurality of differentially produced cellular metabolites having a molecular weight of from about 10 to about 1500 Daltons from hESCs or human pluripotent stem cells; and d) identifying at least one cellular metabolite having a molecular weight of from about 10 to about 1500 Daltons that is differentially produced in cells cultured in the presence of the test compound. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16)
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17. A method for screening a test compound to identify an effect of the compound on human embryonic stem cells (hESCs) or human pluripotent stem cells contacted with the test compound, the method comprising the steps of:
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a) culturing hESCs or human pluripotent stem cells in the presence or absence of a test compound; b) separating members of a population of cellular metabolites having a molecular weight of from about 10 to about 1500 Daltons that are secreted from hESCs or human pluripotent stem cells c) detecting one or a plurality of differentially produced cellular metabolites having a molecular weight of from about 10 to about 1500 Daltons; and d) identifying the effect of a compound on human embryonic stem cells (hESCs) or human pluripotent stem cells by identifying at least one cellular metabolite having a molecular weight of from about 10 to about 1500 Daltons that is differentially secreted between cells cultured in the presence versus the absence of the test compound. - View Dependent Claims (18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32)
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33. A method for assaying a test compound for toxicity or teratogenicity to hESC-derived lineage-specific cells or human pluripotent stem cell-derived lineage-specific cells contacted with the test compound, the method comprising the steps of:
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a) culturing hESC-derived lineage-specific cells or human pluripotent stem cell-derived lineage-specific cells in the presence or absence of a test compound; b) separating members of a population of cellular metabolites having a molecular weight of from about 10 to about 1500 Daltons secreted from or hESC-derived lineage-specific cells or human pluripotent stem cell-derived lineage-specific cells; c) detecting one or a plurality of cellular metabolites having a molecular weight of from about 10 to about 1500 Daltons produced by hESC-derived lineage-specific cells or human pluripotent stem cell-derived lineage-specific cells contacted with a compound; and d) identifying the toxicity or teratogenicity of the test compounds wherein hESC-derived lineage-specific cells or human pluripotent stem cell-derived lineage-specific cells contacted with a test compound differentially produce one or a plurality of cellular metabolites having a molecular weight of from about 10 to about 1500 Daltons. - View Dependent Claims (34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48)
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Specification