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3 Biocybernetics and Biomedical Engineering

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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.

Cell-based clinical and experimental methods for assisting the function of impaired livers – Present and future of liver support systems

Pluta Krzysztof Dariusz, Ciezkowska Malgorzata, Wisniewska Monika, Wencel Agnieszka, Pijanowska Dorota Genowefa

Biocybernetics and Biomedical Engineering

2021

Vol. 41, no. 4

1322--1346

Currently, one of the most serious public health issues is the increasing number of cases of chronic liver disease and cirrhosis both of which can lead to liver failure. The only effective method of treatment for this life-threatening condition remains liver transplantation. Unfortunately, the chronic shortage of transplantable organs seriously limits its accessibility to patients. Thus, tremendous research has been done to develop methods capable of replacing liver transplantation by artificial means or to create techniques to partially or fully replace liver function in patients with impaired livers, until liver regeneration or transplantation. This review article is focused on research results that utilize living cells in order to establish bridging therapies in cases of liver failure. This includes both experimental and clinically tested techniques, such as hepatocyte transplantation and usage of the hybrid bioartificial liver devices. The article also discusses research which presents the long-term culture of hepatocytes in conditions that preserve their differentiated state, which is important for such applications as drug development and toxicity testing. Last but not least, the article describes the groundbreaking efforts toward building sophisticated scaffolds for hepatocyte culture that mimic their natural environment, which are based on decellularized tissues and on three-dimensional bioprinting.

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.