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Toxicity typing using liver stem cells

  • US 8,512,957 B2
  • Filed: 02/21/2012
  • Issued: 08/20/2013
  • Est. Priority Date: 06/14/2000
  • Status: Expired due to Term
First Claim
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1. A first pass method of predicting the type of toxicity of a chemical composition of unknown toxicity, the method comprising the steps of:

  • a) contacting an isolated population of mammalian liver stem cells (LSCs) with the chemical composition of unknown toxicity;

    b) creating a molecular profile identifying the alterations in protein expression in the population of LSCs contacted with the chemical composition of unknown toxicity compared to LSCs in contact with culture medium only;

    c) comparing the molecular profile of LSCs contacted with the chemical compound of unknown toxicity to sets of commonly altered proteins identified from two or more molecular profiles of two or more isolated populations of LSCs wherein each isolated population of LSCs is contacted with one chemical composition of known toxicity, wherein the sets of commonly altered proteins of the chemical compositions having known liver toxicity have been identified byi) contacting each of the two or more isolated populations of mammalian LSCs with one of the chemical compositions having known liver toxicity,ii) creating molecular profiles identifying the alterations in protein expression for each of the two or more populations of LSCs contacted with each of the chemical compositions of known toxicity compared to LSCs in contact with culture medium only, andiii) comparing molecular profiles for known chemical compounds of similar types of toxicity to identify sets of commonly altered proteins for the chemical compounds of similar type of toxicity; and

    d) predicting toxicity of the chemical composition of unknown toxicity wherein common alterations in protein expressions between the sets of commonly altered proteins for chemical compounds of similar types of toxicity and the molecular profile from the LSCs contacted with the compound of unknown toxicity indicate the potential correlation of toxicity between the two.

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