Feridex labeling of mesenchymal stem cells inhibits chondrogenesis but not adipogenesis or osteogenesis

Magnetic resonance (MR) tracking of superparamagnetic iron oxide (SPIO)-labeled cells is a relatively new technique to non-invasively determine the biodistribution and migration of transplanted stem cells. A number of studies have recently reported encouraging results in the use of bone marrow-derived mesenchymal stem cells (MSCs) for repair of a variety of tissues. For MR tracking of SPIO-labeled MSCs, it is important to determine the effect that the magnetic labeling procedure may have on the differentiation capacity of labeled MSCs. Human MSCs were labeled with poly-L-lysine (PLL)-coated Feridex, with Feridex being an FDA-approved SPIO formulation in an off-label application, and assayed for cellular differentiation using five different assays. As compared with unlabeled controls, labeled MSCs exhibited an unaltered viability, proliferated similarly, and underwent normal adipogenic and osteogenic differentiation. However, there was a marked inhibition of chondrogenesis. The blocking of chondrogenic activity was mediated by the Feridex, rather than by the transfection agent (PLL). This is the first report showing Feridex blocking of cellular differentiation down a specific pathway (while not affecting viability and proliferation), and caution should thus be exercised when using Feridex-labeled MSCs for chondrogenic MR tracking studies. On the other hand, no detrimental effects of Feridex-labeling are anticipated for MR-guided osteogenic or adipogenic transplantation studies.