In vitro toxicity screening using human embryonic pluripotent stem cells

• Grant number: 15/01046-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: July 01, 2015
• End date: June 30, 2016
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Lygia da Veiga Pereira
• Grantee: Sofia Lígia Guimarães Ramos
• Host Institution: Instituto de Biociências (IB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 13/08135-2 - CTC - Center for Cell-Based Therapy, AP.CEPID

Abstract

The development of a new drug takes approximately ten years and it requires a major investment of capital. Even after the drug is commercialized, there are still efficiency and toxicology issues. Some drugs tested in Europe or North America do not have the same effect on the Brazilian population and this is mainly due to the different genetic background, which influences drug response. Our laboratory is making a library of human induced pluripotent stem cells lines (hiPSCs), derived from blood samples. These samples come from the ELSA blood bank, which represents the genetic heterogeneity of the Brazilian population. Our long term goal is to evaluate the hiPSCs capacity as an in vitro model for drug toxicity and efficiency tests. To do so, we have already developed a differentiation protocol to derive hiPSCs into hepatocytes. Nevertheless, before we use the hiPSCs we need to set up a dose-response curve using hepatocytes derived from embryonic human stem cell lines in order to establish the appropriate dose and time of incubation for the metabolization of fluoxetin, an antidepressant.