Biofabrication of Layered Membrane Systems by Using Human Hepatocytes and Endothelial Cells: A Comparative Study
Simona Salerno, Sabrina Morelli, Enrico Drioli, Augustinus Bader and Loredana de Bartolo
Affiliation: Institute on Membrane Technology, National Research Council of Italy, ITM-CNR, c/o University of Calabria, cubo 17/C, Via P. Bucci, I-87030 Rende (CS), Italy.
Strategies to overcome in vitro dedifferentiation of hepatocytes preserving key features of the liver phenotype
in vitro constitute a major goal in medical applications. The realization of biohybrid membrane systems, utilizing primary
human hepatocytes in co-culture with non-parenchymal cells and polymeric membranes with suitable properties, offered
interesting opportunities for the design of bioartificial liver. This study was aimed to investigate the morphological and
functional behavior of primary human hepatocytes with endothelial cells (ECs) in two different layered co-culture membrane
systems, which were realized by using a synthetic polymeric membrane and two different sequential cell seeding
methods. We evaluated the heterotypic cell-cell interactions in the different layered membrane systems in order to understand
if the variation of the heterotypic interface between hepatocytes and ECs and of cell type interacting with membrane
may influence the performance of functional biofabricated hepatocellular constructs. Overall results demonstrated a strong
influence of the heterotypic interactions on the performance of the tissue constructs in terms of albumin secretion, urea
synthesis and drug biotransformation functions.
Keywords: Biohybrid membrane systems, endothelial cells, hepatocytes, hepatocellular constructs, heterotypic interactions,
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