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Investigation of possible etoposide-induced hepatocyte maturation mechanisms in vitro

Grant number: 19/19380-4
Support type:Scholarships in Brazil - Doctorate (Direct)
Effective date (Start): November 01, 2019
Effective date (End): October 31, 2022
Field of knowledge:Biological Sciences - Biochemistry
Principal Investigator:Mayana Zatz
Grantee:Kayque Alves Telles Silva
Home Institution: Instituto de Biociências (IB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

The liver is a crucial organ regarding metabolic, immune and homeostatic regulation. Chronic and acute liver diseases, congenital or behavioral, accounts for approximately 2 million deaths per year. The only therapeutic options to severe liver diseases are partial or total liver transplantation. Hepatic tissue engineering, allied to human induced pluripotent stem cells (hiPSCs) technology, comprises an alternative to traditional therapeutic procedures. Hepatocytes differentiation protocols, nevertheless, results in hepatocytes with fetal phenotype, hampering the comprehension about adult liver cells mechanisms and the development of regenerative medicine approaches. Previous experiments revealed that the application of etoposide (VP-16), an apoptosis inducer small molecule, in hiPSC-derived hepatocytes contributed to the induction of cellular maturation. This project aims to investigate the possible mechanisms involved in the maturation of hiPSC-derived hepatocytes treated with etoposide. hiPSCs already reprogrammed from healthy patients fibroblasts and peripheral blood cells will be differentiated into hepatocyte-like cells (HLCs). Etoposide-treated HLCs maturation level and involved mechanisms will be evaluated through flow cytometry, immunofluorescence (IF), RT-qPCR and RNA-Seq. (AU)