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Development of universal hepatic organoids produced from IPS cells

Grant number: 19/18469-1
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): September 01, 2019
Effective date (End): August 31, 2020
Field of knowledge:Biological Sciences - Genetics
Principal Investigator:Mayana Zatz
Grantee:Ernesto da Silveira Goulart Guimarães
Home Institution: Instituto de Biociências (IB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated research grant:13/08028-1 - CEGH-CEL - Human Genome and Stem Cell Research Center, AP.CEPID

Abstract

Hepatic organoid technology holds great promise for the development of future Regenerative Medicine strategies to treat patients with severe liver disease. Recently, some studies have demonstrated robust protocols for isogenic organoid generation using induced Pluripotent Stem cells (iPS). However, using patient's specific iPS-derived cells poses a major challenge for a translational perspective. Self-recognizing protein gene editing protocols, i.e. HLA, using CRISPR-Cas9 technology can produce universal donor cells. However, none of the current universal cell production protocols has been completely effective in evading NK and CD8 + cytolytic cells. Similarly, liver grafting and functional replacement capacity of hepatic organoids obtained from universal iPS have also never been tested. Thus, the aim of this work is to investigate a new iPS cell gene editing strategy aiming the production of a universal donor cell line and to evaluate the efficiency of cytolytic escape using differentiated liver organoids obtained from the final produced cell line. (AU)