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Hollow fiber bioreactor with genetically modified hepatic cells as a model of biologically active function block of the bioartificial liver

Jakubowska Małgorzata, Wisniewska Monika Joanna, Wencel Agnieszka, Wojciechowski Cezary, Gora Monika, Dudek Krzysztof, Chwojnowski Andrzej, Burzynska Beata, Pijanowska Dorota Genowefa, Pluta Krzysztof Dariusz

Biocybernetics and Biomedical Engineering

2024

Vol. 44, no. 1

9--19

Chronic liver disease and cirrhosis, that can lead to liver failure, are major public health issues, with liver transplantation as the only effective treatment. However, the limited availability of transplantable organs has spurred research into alternative therapies, including bioartificial livers. To date, liver hybrid support devices, using porcine hepatocytes or hepatoma-derived cell lines, have failed to demonstrate efficacy in clinical trials. Here, for the first time, we report the construction of a model of biologically active function block of bioartificial liver based on a hollow fiber bioreactor populated with genetically modified hepatic cells. For comprehensive comparison the culturing of hepatic cells was carried out in both static and dynamic conditions in a medium that flowed through porous polysulfone capillaries. The most crucial parameters, such as cell viability, glucose consumption, albumin secretion and urea production, were analyzed in static conditions while glucose usage and albumin production were compared in dynamic cell cultures. This model has the potential to improve the development of bioartificial liver devices and contribute to the treatment of patients with impaired liver function.

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.