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Analysis of Topoisomerase 2 inhibitors on in vitro hepatic differentiation

Grant number: 21/04113-0
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): June 01, 2021
Effective date (End): January 31, 2023
Field of knowledge:Biological Sciences - Genetics - Human and Medical Genetics
Principal researcher:Mayana Zatz
Grantee:Lara Borges Pacheco
Home Institution: Instituto de Biociências (IB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

The liver is the second largest solid organ of the human body, playing an important role in the maintenance of the homeostasis. Hepatic pathologies can be fatal, while the only therapeutic option is transplantation. However, there are some problems regarding liver transplants: the increasing waiting list is not accompanied by a rise in donors; the need to use immunosuppressant after surgery and the occurrence of biliary complications, such as biliary duct leaks and anastomotic strictures. Developing techniques involving bioengineering and cellular biology, likedecellularization and recellularization of livers with healthy hepatocytes, represents an alternative to traditional transplant approaches. Nevertheless, there are some challenges concerning these techniques, such as the lack of a well established recellularization protocol and the difficulty to generate mature hepatocytes in vitro. This work aims to evaluate formulations that inhibit the Topoisomerase enzyme, leading to DNA double-strand breaks, in order to evaluate if the stress improves hepatocyte-like cells maturation. Hepatocytes will be differentiated from human iPSC. Hepatic maturation will be evaluated by RT-PCR and immunofluorescence (IF). (AU)

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