pplied Hepatic Bioengineering: Modeling the Human Liver Using Organoid and Liver-on-a-Chip Technologie

Author(s)

Telles-Silva, Kayque Alves ^[1] ; Pacheco, Lara ^[1] ; Komatsu, Sabrina ^[1] ; Chianca, Fernanda ^[1] ; Caires-Junior, Luiz Carlos ^[1] ; Araujo, Bruno Henrique Silva ^[2] ; Goulart, Ernesto ^[1] ; Zatz, Mayana ^[1]

Affiliation

^[1] Univ Sao Paulo, Inst Biosci, Human Genome & Stem Cell Res Ctr HUG CEL, Sao Paulo - Brazil

^[2] Johns Hopkins Univ, Sch Med, Lieber Inst Brain Dev, Baltimore, MD - USA

• Document type: Review article
• Source: FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY; v. 10, FEB 14 2022.
• Web of Science Citations: 0

Abstract

The liver is the most important metabolic hub of endo and xenobiotic compounds. Pre-clinical studies using rodents to evaluate the toxicity of new drugs and cosmetics may produce inconclusive results for predicting clinical outcomes in humans, moreover being banned in the European Union. Human liver modeling using primary hepatocytes presents low reproducibility due to batch-to-batch variability, while iPSC-derived hepatocytes in monolayer cultures (2D) show reduced cellular functionality. Here we review the current status of the two most robust in vitro approaches in improving hepatocyte phenotype and metabolism while mimicking the hepatic physiological microenvironment: organoids and liver-on-chip. Both technologies are reviewed in design and manufacturing techniques, following cellular composition and functionality. Furthermore, drug screening and liver diseases modeling efficiencies are summarized. Finally, organoid and liver-on-chip technologies are compared regarding advantages and limitations, aiming to guide the selection of appropriate models for translational research and the development of such technologies. (AU)

• FAPESP's process: 19/18469-1 - Development of universal hepatic organoids produced from IPS cells
• Grantee: Ernesto da Silveira Goulart Guimarães
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 21/04113-0 - Analysis of Topoisomerase 2 inhibitors on in vitro hepatic differentiation
• Grantee: Lara Borges Pacheco
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 19/19380-4 - Investigation of possible etoposide-induced hepatocyte maturation mechanisms in vitro
• Grantee: Kayque Alves Telles Silva
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• FAPESP's process: 17/16283-2 - Development of tissue bioengineering techniques for the functional reconstruction of ex vivo iPSC cell livers
• Grantee: Luiz Carlos de Caires Júnior
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 13/08028-1 - CEGH-CEL - Human Genome and Stem Cell Research Center
• Grantee: Mayana Zatz
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 21/04121-3 - Analysis of etoposide on in vitro cardiac differentiation
• Grantee: Sabrina Kaori Kadowaki Komatsu
• Support Opportunities: Scholarships in Brazil - Scientific Initiation