Metabolomics Based Comparison of Human Embryonic and Induced Pluripotent Stem Cells to Predict Developmental Toxicity

Induced pluripotent stem (iPS) cells are derived from the genetic manipulation of somatic cells. These cells are being investigated for use in place of hES cells due to the moral, ethical and political controversies that surround them. Human iPS cells are phenotypically and genetically similar to hES cells in many respects (i.e. morphology, proliferation, gene expression). However, the metabolic similarity between hES cells and iPS cells is not known. It is vital to understand this information when considering using iPS cells in the same manner as hES cells, such as for human toxicity testing.  Using a metabolomic approach, we evaluated 227 mass features by LC/MS that may represent secreted metabolites (secretome) across three hES cell lines and two iPS cell lines.  Our data shows minimal differences exist in the secretome between cell types. Additionally, we exposed both cell types to a training set of pharmaceuticals with known teratogenicity (Table 1) and identified a cell line specific metabolic signature capable of predicting teratogenicity as assessed using a blinded test set of compounds of known teratogenicity. Pathway enrichment analysis of statistically significant, differentially metabolized putative compounds identified pathways that were disrupted in multiple teratogen treatments.

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