Magnetic iron microbeads coupled with HEA-125 monoclonal antibody against epithelial cell adhesion molecule

Excerpt

Magnetic iron microbeads coupled with HEA-125 monoclonal antibody against the epithelial cell adhesion molecule (EpCAM), abbreviated as EpCAM microbeads, have been developed primarily for the positive selection or depletion of EpCAM-positive cells (1, 2). McClelland et al. have demonstrated the feasibility of cell tracking with magnetic resonance imaging (MRI) after the hepatic progenitor cells are labeled with EpCAM microbeads (1).

Superparamagnetic iron oxide (SPIO)-based agents have been intensively tested for use in cell tracking with MRI in both preclinical and clinical situations (3, 4). SPIO particles provide a strong change in signal per unit of metal in T2-weighted images without a significant effect on labeled cells and host (3, 5). For efficient cell labeling, SPIO particles are generally coated with low-molecular-weight polymers or dendrimers leading to clusters of electron-dense crystal cores covered with the polymer or dendrimer. Surface coating increases the stability of SPIO particles and allows further chemical modification of the particles with targeting ligands. Cell tracking studies have shown that the migration and homing capabilities of SPIO-labeled cells can be monitored in vivo over days to months (3, 4, 6).

Nevertheless, there are still many challenges to overcome before MRI cell tracking can be considered a robust technique in preclinical settings or in clinical applications (3, 7). MRI detects the presence of SPIO contrast agents, regardless of whether SPIO particles remain in the relevant cells, are lost to the extracellular matrix, or are transferred to other cells. It is still not possible to use MRI to discriminate live cells from dead cells or relevant cells from phagocytes. Detection sensitivity also becomes an issue when cells actively divide and migrate, in which case the SPIO labels are quickly divided among daughter cells to levels that are undetectable with MRI. In vivo quantification of the cell number is more challenging because of the contrast agent dilution during cell division, contrast agent transfer to others cells, other sources of iron in tissue, and technical limitations (4, 7).

McClelland et al. addressed the problem of contrast agent dilution in MRI cell tracking by using EpCAM microbeads as the label (1). The human EpCAM, also known as CD326 or epithelial-specific antigen, is a cell-surface antigen and is found on hepatic progenitor cells, including human hepatic stem cells (hHpSCs) and hepatoblasts (hHBs), on liver cancer stem cells, and on proliferating epithelial cells in other tissues (8-10). The human EpCAM is not expressed in animal cells. McClelland et al. studied the labeling of hHpSCs with EpCAM microbeads in vitro, ex vivo, and in vivo and imaged the labeled cells with MRI (1). The investigators demonstrated that the hHpSCs could be labeled with EpCAM microbeads before or after transplantation, and the transplanted hHpSCs could be monitored and counted repeatedly in the same host by injection of the label just prior to MRI (1).