Rodrigo M. Florentino, PhD, Postdoctoral Associate in the lab of Dr. Alex Soto-Gutierrez, and 2022 PLRC DANDI award winner, published a manuscript in iScience entitled, “Biofabrication of synthetic human liver tissue with advanced programmable functions”.
Florentino RM, Morita K, Haep N, Motomura T, Diaz-Aragon R, Faccioli LAP, Collin de l’Hortet A, Cetin Z, Frau C, Vernetti L, Amler AK, Thomas A, Lam T, Kloke L, Takeishi K, Taylor DL, Fox IJ, Soto-Gutierrez A. Biofabrication of synthetic human liver tissue with advanced programmable functions. iScience. 2022 Nov 4;25(12):105503. doi: 10.1016/j.isci.2022.105503. PMID: 36404924; PMCID: PMC9672940.
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.