Biofabrication of synthetic human liver tissue with advanced programmable functions

Advances in cellular engineering, as well as gene, and cell therapy, may be used to produce human tissues with programmable genetically enhanced functions designed to model and/or treat specific diseases. Fabrication of synthetic human liver tissue with these programmable functions has not been desc...

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Published in:iScience 2022-12, Vol.25 (12), p.105503, Article 105503
Main Authors: Florentino, Rodrigo M., Morita, Kazutoyo, Haep, Nils, Motomura, Takashi, Diaz-Aragon, Ricardo, Faccioli, Lanuza A.P., Collin de l’Hortet, Alexandra, Cetin, Zeliha, Frau, Carla, Vernetti, Lawrence, Amler, Anna-Klara, Thomas, Alexander, Lam, Tobias, Kloke, Lutz, Takeishi, Kazuki, Taylor, D. Lansing, Fox, Ira J., Soto-Gutierrez, Alejandro
Format: Article
Language:English
Subjects:
Bioengineering
Biological sciences
Tissue engineering
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Summary:Advances in cellular engineering, as well as gene, and cell therapy, may be used to produce human tissues with programmable genetically enhanced functions designed to model and/or treat specific diseases. Fabrication of synthetic human liver tissue with these programmable functions has not been described. By generating human iPSCs with target gene expression controlled by a guide RNA-directed CRISPR-Cas9 synergistic-activation-mediator, we produced synthetic human liver tissues with programmable functions. Such iPSCs were guide-RNA-treated to enhance expression of the clinically relevant CYP3A4 and UGT1A1 genes, and after hepatocyte-directed differentiation, cells demonstrated enhanced functions compared to those found in primary human hepatocytes. We then generated human liver tissue with these synthetic human iPSC-derived hepatocytes (iHeps) and other non-parenchymal cells demonstrating advanced programmable functions. Fabrication of synthetic human liver tissue with modifiable functional genetic programs may be a useful tool for drug discovery, investigating biology, and potentially creating bioengineered organs with specialized functions. [Display omitted] •Edited human iPSCsgain can control transcriptional activation•CYP3A4 and UGT1A1 activity in human iHepsgain are similar to human hepatocytes•Human iHepsgain generate synthetic liver tissue with advanced programmable functions Biological sciences; Bioengineering; Tissue engineering
ISSN:2589-0042
2589-0042
DOI:10.1016/j.isci.2022.105503