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1 2020

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Genetically modified C3A cells with restored urea cycle for improved bioartificial liver

Pluta Krzysztof Dariusz, Samluk Anna, Wencel Agnieszka, Zakrzewska Karolina Ewa, Gora Monika, Burzynska Beata, Ciezkowska Malgorzata, Motyl Joanna, Pijanowska Dorota Genowefa

Biocybernetics and Biomedical Engineering

2020

Vol. 40, no. 1

378--387

The bioartificial liver, a hybrid device aimed at improving the survival of patients with fulminant liver failure, requires a cell source to replicate human liver function. However, liver support systems that utilize porcine or human hepatoma-derived cells felt short of expectations in clinical trials. Here we present engineered C3A cells, with a restored function of the urea cycle, which can be used in an efficacious bioartificial liver. The genetic modification was performed using a lentiviral-mediated gene transfer which led to effective integra- tion of the transgenes, coding for arginase I and ornithine transcarbamylase, into the target cell genomes. The engineered cells are more resistant to the oxidative/nitrosative stress induced by the presence of high concentrations of ammonia cations and produce more urea than their unmodified counterparts. Interestingly, the genetically modified cells secrete more albumin than control C3A cells and the synthesis of the protein is induced by increasing concentrations of ammonia. Although the physiological capabilities of the new cell line need to be further examined, at this stage of our study we may conclude that the genetically modified cells are able to convert ammonia to urea more effectively than regular C3A cells.