Investigation of possible etoposide-induced hepatocyte maturation mechanisms in vitro

• Grant number: 22/08157-5
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate (Direct)
• Start date: October 17, 2022
• End date: October 16, 2023
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Mayana Zatz
• Grantee: Kayque Alves Telles Silva
• Supervisor: Holger Willenbring
• Host Institution: Instituto de Biociências (IB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Institution abroad: University of California, San Francisco (UCSF), United States
• Associated to the scholarship: 19/19380-4 - Investigation of possible etoposide-induced hepatocyte maturation mechanisms in vitro, BP.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)

GROEGER, MARKO; MATSUO, KOJI; ARASH, EMAD HEIDARY; PEREIRA, ASHLEY; LE GUILLOU, DOUNIA; PINO, CINDY; TELLES-SILVA, KAYQUE A.; MAHER, JACQUELYN J.; HSIAO, EDWARD C.; WILLENBRING, HOLGER. Modeling and therapeutic targeting of inflammation-induced hepatic insulin resistance using human iPSC-derived hepatocytes and macrophages. NATURE COMMUNICATIONS, v. 14, n. 1, p. 14-pg., 2023-07-03. (22/08157-5)