Reagents and methods for using human embryonic stem cells to evaluate toxicity of pharmaceutical compounds and other chemicals

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.

1 - 54 . (canceled) 
     
     
         55 . A biomarker profile for identifying a toxic compound, wherein the biomarker profile comprises one or a plurality of cellular metabolites having a molecular weight of from about 10 to about 1500 Daltons that are differentially produced in human embryonic stem cells (hESCs) or hESC-derived lineage-specific cells contacted with a toxic compound or compounds, wherein the profile was identified from a population of cellular metabolites secreted from the cells. 
     
     
         56 . A biomarker profile of  claim 55 , comprising tetrahydrofolate, dihydrofolate or other metabolites in the folate metabolic pathway, glutathione, or oxidized glutathione. 
     
     
         57 . A biomarker profile of  claim 55 , comprising kynurenine, 8-methoxykynurenate, N′-formylkynurenine 7,8-dihydro-7,8-dihydroxykynurenate 5-Hydroxytryptophan, N-acetyl-D-tryptophan, glutamate, pyroglutamic acid or other metabolites in the tryptophan or glutamate metabolic pathways, histamine, dopamine, 3,4-dihydroxybutyric acid, serotonin, gamma-aminobutyric acid (GABA) or other butyric acid species.