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

Publication date: Available online 9 January 2020Source: Biocybernetics and Biomedical EngineeringAuthor(s): Krzysztof Dariusz Pluta, Anna Samluk, Agnieszka Wencel, Karolina Ewa Zakrzewska, Monika Gora, Beata Burzynska, Malgorzata Ciezkowska, Joanna Motyl, Dorota Genowefa PijanowskaAbstractThe 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 integration 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...

Source: Biocybernetics and Biomedical Engineering - January 10, 2020 Category: Biomedical Engineering Source Type: research