Development of universal hepatic organoids produced from IPS cells

• Grant number: 19/18469-1
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: September 01, 2019
• End date: April 27, 2023
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Principal Investigator: Mayana Zatz
• Grantee: Ernesto da Silveira Goulart Guimarães
• Host 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)

Scientific publications

(4)

(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)

FIGUEIREDO, THALITA; MENDES, ANA P. D.; MOREIRA, DANIELLE P.; GOULART, ERNESTO; OLIVEIRA, DANYLLO; KOBAYASHI, GERSON S.; STERN, SHANI; KOK, FERNANDO; MARCHETTO, MARIA C.; SANTOS, RENATA; et al. Inositol monophosphatase 1 (IMPA1) mutation in intellectual disability patients impairs neurogenesis but not gliogenesis. MOLECULAR PSYCHIATRY, AUG 2020. (19/18469-1, 13/08028-1, 17/19877-0, 14/50931-3, 16/09618-5)

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)

FIGUEIREDO, THALITA; MENDES, ANA P. D.; MOREIRA, DANIELLE P.; GOULART, ERNESTO; OLIVEIRA, DANYLLO; KOBAYASHI, GERSON S.; STERN, SHANI; KOK, FERNANDO; MARCHETTO, MARIA C.; SANTOS, RENATA; et al. Inositol monophosphatase 1 (IMPA1) mutation in intellectual disability patients impairs neurogenesis but not gliogenesis. MOLECULAR PSYCHIATRY, v. 26, n. 7, p. 3558-3571, JUL 2021. (16/09618-5, 17/19877-0, 13/08028-1, 19/18469-1, 14/50931-3)

GARCIA-ROSA, SHEILA; BRENHA, BIANCA DE FREITAS; DA ROCHA, VINICIUS FELIPE; GOULART, ERNESTO; SILVA ARAUJO, BRUNO HENRIQUE. Personalized Medicine Using Cutting Edge Technologies for Genetic Epilepsies. Current Neuropharmacology, v. 19, n. 6, p. 813-831, 2021. (19/18469-1)