Investigation of possible etoposide-induced hepatocyte maturation mechanisms in vitro

• Grant number: 19/19380-4
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: November 01, 2019
• End date: October 31, 2025
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Mayana Zatz
• Grantee: Kayque Alves Telles Silva
• Host Institution: Instituto de Biociências (IB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated scholarship(s): 22/08157-5 - Investigation of possible etoposide-induced hepatocyte maturation mechanisms in vitro, BE.EP.DD

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)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

TELLES-SILVA, KAYQUE ALVES; PACHECO, LARA; CHIANCA, FERNANDA; KOMATSU, SABRINA; CHIOVATTO, CAROLINE; ZATZ, MAYANA; GOULART, ERNESTO. iPSC-derived cells for whole liver bioengineering. FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY, v. 12, p. 8-pg., 2024-02-07. (22/08157-5, 21/11872-5, 19/19380-4, 13/08028-1)

TELLES-SILVA, KAYQUE ALVES; PACHECO, LARA; KOMATSU, SABRINA; CHIANCA, FERNANDA; CAIRES-JUNIOR, LUIZ CARLOS; ARAUJO, BRUNO HENRIQUE SILVA; GOULART, ERNESTO; ZATZ, MAYANA. pplied Hepatic Bioengineering: Modeling the Human Liver Using Organoid and Liver-on-a-Chip Technologie. FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY, v. 10, FEB 14 2022. (19/18469-1, 21/04113-0, 19/19380-4, 17/16283-2, 13/08028-1, 21/04121-3)