Hepatocyte hollow-fibre bioreactors: design, set-up, validation and applications

Abstract

Hepatocytes carry out many vital biological functions, such as synthetic and catabolic reactions, detoxification and excretion. Due to their ability to restore a tissue-like environment, hollow-fibre bioreactors (HFBs) show great potential among the different systems used to culture hepatocytes. Several designs of HFBs have been proposed in which hepatocytes or hepatocyte-derived cell lines can be cultured in suspensions or on a solid support. Currently the major use of hepatocyte HFBs is as bioartificial livers to sustain patients suffering from acute liver failure, but they can also be used to synthesize cell products and as cellular models for drug metabolism and transport studies. Here, we present an overview of the set-up of hepatocyte HFBs and aim to provide potential users with the basic knowledge necessary to develop their own system. First, general information on HFBs is given, including basic principles, transport phenomena, designs and cell culture conditions. The importance of the tests necessary to assess the performance of the HFBs, i.e. the viability and functionality of hepatocytes, is underlined. Special attention is paid to drug metabolism studies and to adequate analytical methods. Finally, the potential uses of hepatocyte HFBs are described.

Adhesion contact dynamics of primary hepatocytes on poly(ethylene terephthalate) surface

“…A bioartificial liver assist device (BLAD) that can provide the critical hepatic functions would be extremely valuable to ALF patients [2]. In general, BLADs containing active hepatocytes take in plasma from haemodialysis unit for carrying the essential metabolic functions [3]. One of the keys in BLAD development is the design of effective biomaterial surface or scaffold for hepatocyte attachment, e.g., poly(l-lactic acid) [4,5].…”

Gd-BOPTA Transport Into Rat Hepatocytes: Pharmacokinetic Analysis of Dynamic Magnetic Resonance Images Using a Hollow-Fiber Bioreactor

“…Hollow-fiber bioreactors (HFBs) have the advantage to restore a physiological environment that ensures the viability and functionality of cells. 13 The aim of the study was to compare the kinetics of the MR signal intensity (SI) over time during the perfusion of Gd-DTPA and Gd-BOPTA in an MR-compatible HFB containing freshly isolated rat hepatocytes in suspension and to determine whether the hepatocyte transport of Gd-BOPTA might be better defined by a compartmental pharmacokinetic analysis.…”

In Vitro Methods to Study Chemically-Induced Hepatotoxicity: A Literature Review

“…In order to remedy this issue, several perfused bioreactors were developed. The earliest flowthrough bioreactors were hollow fiber bioreactors, which are used today to sustain patients with acute liver failure [111], but they have also been tested as in vitro models of drug metabolism. Hollow fibers have been shown to maintain hepatocyte morphology such as bile canaliculi and intercellular junctions even seven days after culture [112].…”