Hollow fiber bioreactor: New development for the study of contrast agent transport into hepatocytes by magnetic resonance imaging

Abstract

The aim of our study was to develop a magnetic resonance (MR)-compatible in vitro model containing freshly isolated rat hepatocytes to study the transport of hepatobiliary contrast agents (CA) by MR imaging (MRI). We set up a perfusion system including a perfusion circuit, a heating device, an oxygenator, and a hollow fiber bioreactor (HFB). The role of the porosity and surface of the hollow fiber (HF) as well as the perfusate flow rate applied on the diffusion of CAs and O 2 was determined. Hepatocytes were isolated and injected in the extracapillary space of the HFB (4 Â 10 7 cells/mL). The hepatocyte HFB was perfused with an extracellular CA, gadopentetate dimeglumine (Gd-DTPA), and gadobenate dimeglumine (Gd-BOPTA), which also enters into hepatocytes. The HFB was imaged in the MR room using a dynamic T 1 -weighed sequence. No adsorption of CAs was detected in the perfusion system without hepatocytes. The use of a membrane with a high porosity (0.5 Am) and surface (420 cm 2 ), and a high flow rate perfusion (100 mL/min) resulted in a rapid filling of the HFB with CAs. The cellular viability of hepatocytes in the HFB was greater than 85% and the O 2 consumption was maintained over the experimental period. The kinetics of MR signal intensity (SI) clearly showed the different behavior of Gd-BOPTA that enters into hepatocytes and Gd-DTPA that remains extracellular. Thus, these results show that our newly developed in vitro model is an interesting tool to investigate the transport kinetics of hepatobiliary CAs by measuring the MR SI over time. B 2004 Wiley Periodicals, Inc.

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

“…24 Briefly, it includes a closed perfusion circuit, a heating device, a silicone membrane oxygenator, and a HFB consisting of a network of semipermeable artificial capillaries bundled together within a transparent plastic shell (Fig. 2).…”

New advances in MR‐compatible bioartificial liver

“…These early suspension and, more recently, perfused BAL studies focused on short‐term xenobiotic perturbation and were not intended for long‐term use (see suspension category references in Table 1). However, some have focused on the characterization of the function and imaging cell distribution for tissue engineering analysis 29, 59, 69, and this review demonstrates the application of multinuclear MRS using 31 P (Figs 4 and 9), 13 C (Fig. 10), 19 F (Fig.…”

“…Planchamp et al . 35, 69 used a hollow fiber BAL inoculated with rat hepatocytes as a model to investigate the pharmacokinetics of contrast agents employing dynamic T 1 ‐weighted FAST. The goal was not to use MRI to determine the distribution or function of the tissue‐engineered system, but rather to use BAL as a liver model to investigate the disposition and biotransport of the imaging contrast agent, gadolinium benzyl‐oxypropionictetraacetate.…”

In vitro experimental study of the relationship between the apparent diffusion coefficient and changes in cellularity and cell morphology

“…There are several methods of conducting MR imaging of cells, including the use of cell pellets (14), gelatinous material including cells (15)(16)(17)(18)(19), and particular instruments for cell culture (9,20). Only two reports (9,20) have investigated the ADC values of cells using a particular cell culture device referred to as a 'Hollow fiber' device together with an experimental MRI system. This is the first report of the ADC values of cells using cell pellets, gelatinous material containing cells, and a clinical MRI system.…”