Effects of genetically modified human skin fibroblasts, stably overexpressing hepatocyte growth factor, on hepatic functions of cocultured C3A cells.

Diseases leading to terminal hepatic failure are among the most common causes of death worldwide. Transplant of the whole organ is the only effective method to cure liver failure. Unfortunately, this treatment option is not available universally due to the serious shortage of donors. Thus, alternative methods have been developed that are aimed at prolonging the life of patients, including hepatic cells transplantation and bridging therapy based on hybrid bioartificial liver devices. Parenchymal liver cells are highly differentiated and perform many complex functions, such as detoxification and protein synthesis. Unfortunately, isolated hepatocytes display a rapid decline in viability and liver-specific functions. A number of methods have been developed to maintain hepatocytes in their highly differentiated state in vitro, amongst them the most promising being 3D growth scaffolds and decellularized tissues or coculture with other cell types required for the heterotypic cell-cell interactions. Here we present a novel approach to the hepatic cells culture based on the feeder layer cells genetically modified using lentiviral vector to stably produce additional amounts of hepatocyte growth factor and show the positive influence of these coculture conditions on the preservation of the hepatic functions of the liver parenchymal cells' model-C3A cells.

Clinical applications of liver support systems / Kliniczne metody wspomagania niewydolnej watroby.

Liver diseases that lead to its failure are one of the most frequent causes of death worldwide. Taking into account liver's complexity, there are no drug for acute or acute on chronic liver failure treatment. So far the only effective therapy is the liver transplantation. Unfortunately donor shortage is a main problem of this therapy. Due to this fact scientists have been looking for a new alternatives. The most promising are cell transplantation and bioartificial support systems. Without doubt hepatocytes are the best source of cells to use. But isolated human hepatocytes dedifferentiate very quickly and lose their functions ex vivo. Therefore, the new sources of cells, which could replace hepatocytes, are highly sought after. It is believed that, in order to help patients suffering from liver disease, the approach to solve this problem should be considered on different levels.