Organ cross-talk in a multi compartment connected culture bioreactor

In vitro models suffer from the absence of a multitude of factors, including adequate physical stimuli and the lack of interaction and cross-talk between different tissues. Although microfluidic systems with multi cell chambers have been proposed, they often require specialized liquid handling and manipulation to be of general laboratory use. Here we describe the design and realization of the system, and report on the results of a metabolic study and a toxicity study. The MCB bioreactor system, commercialized under the name Quasi-VivoTM by Kirkstall Ltd, UK, consists of multi-well sized modules. It is a flexible, easily configurable and offers a medium throughput tool for analyzing cell-cell cross talk. Cells and tissues can be cultured in the presence of a common medium which flows through the system acting as the bloodstream. Primary rat hepatocytes and visceral fat were cultured separately and together in conventional conditions and in the bioreactor. Urea synthesis, albumin secretion and glucose and glycerol concentrations were analyzed at different time points and compared. The presence of both cell types in a flow through system leads to a constant physiological glycerol concentration as well as upregulation of albumin In a different set of experiments, primary rat hepatocytes and glisarcaoma cells were cultured in the MCB system and exposed to different concentrations of dichlofenac, a hepatotoxic drug. Cell vitality, albumin, urea, glucose concentrations as well as apoptosis and oxidative stress were measured. The IC50 concentration in the bioreactor was much closer to typical in vivo concentrations found in patient serum. In both studies we show that cells behave in a more physiological manner in the bioreactor, demonstrating that the MCB brings the system closer to an in vivo environment.