Tissue Engineering Using Magnetite Nanoparticles and Magnetic Force: Heterotypic Layers of Cocultured Hepatocytes and Endothelial Cells

Abstract

Novel technologies to establish three-dimensional, in vivo-like tissue consisting of various types of cells are required for tissue engineering. We applied magnetic force to construct a heterotypic, layered coculture system of rat hepatocytes and human aortic endothelial cells (HAECs) that was not limited by cell type. Magnetite cationic liposomes carrying a positive surface charge to improve adsorption accumulated in HAECs at a concentration of 38 pg of magnetite per cell. Magnetically labeled HAECs specifically accumulated onto hepatocyte monolayers at sites where a magnet (4000 G) was positioned, and then adhered to form a heterotypic, layered construct with tight and close contact. This cocultured construct significantly (p < 0.05) enhanced albumin secretion by hepatocytes compared with that in homotypic cultures of hepatocytes or heterotypic cocultures of hepatocytes and HAECs without magnets. These results suggest that this novel use of magnetite nanoparticles and magnetic force, which we refer to as "magnetic force-based tissue engineering" (Mag-TE), offers a major advancement in tissue engineering.

Cell surface engineering with polyelectrolyte-stabilized magnetic nanoparticles: A facile approach for fabrication of artificial multicellular tissue-mimicking clusters

“…Current tissue engineering techniques based on intracellular magnetization of cells have extensively used magnetically labeled cells for fabrication of layered structures [3] or multicellular spheroids [36]. We employed magnetically functionalized A549 and HSF cells for fabrication of artificial lung-mimicking layered tissue-like constructs [20].…”

“…Magnetically facilitated tissue engineering employs the introduction of magnetic nanoparticles (MNPs) into or onto live cells as an effective means for remote magnetic field-based control of spatial deposition of cells and fabrication of layered tissue-like structures [3]. Over the past decade, researchers worldwide have focused on the elaboration of novel techniques for the effective magnetic functionalization of mammalian cells and their subsequent use for controllable cell assembly.…”

Can Magnetic Targeting of Magnetically Labeled Circulating Cells Optimize Intramyocardial Cell Retention?

“…Magnetic control of cell motion has already been used in basic studies of cell fluorescein isothiocyanate (FITC), anti-CD144 phycoerythrin (PE; Becton Dickinson), anti-vascular endothelial mechanics (40), cell sorting applications (29), and tissue engineering (14,22). In the field of cell therapy, maggrowth factor receptor 2 allophycocyanin (VEGFR2-APC; Sigma), and anti-von Willebrand factor (vWF) netic targeting was first used to enhance liver cell transplantation (4, 26) and was recently shown to facilitate (Dako).…”

Coating Nanomagnetic Particles for Biomedical Applications

“…In this study, HAECs accumulated onto hepatocyte monolayers at sites where a magnet was positioned, and then adhered to form heterotypic, layered construct with tight and close contact. Albumin secretion was enhanced in the homotypic hepatocyte culture in presence of a magnetic force compared with the culture without magnets (Ito et al, 2004c).…”