Chondrocyte Gene Expression is Affected by Very Small Iron Oxide Particles-Labeling in Long-Term in Vitro MRI Tracking

Purpose: To investigate the effect and dose response of very small iron oxide particles (VSOP) labeling of human chondrocytes for long-term in vitro MRI tracking. Materials and Methods: Chondrocytes were isolated from cartilage biopsies from four patients. The cells for the dose-response study were labeled with 25, 50, or 100 mu g/mL VSOP. Quantitative gene expression and cellular proliferation were compared with unlabeled controls at day 1, 3, and 7. The cells suited for MRI tracking were labeled with 50 mu g/mL VSOP and embedded in alginate beads, followed by MRI (using T2-weighted sequences) at day 0, 1, 3, 7, 14. 21, 28, and histology was performed at each time-point. Results: Histology revealed that VSOP particles were intracellularly confined at all time-points, whereas no extracellular VSOPs were observed. A mean reduction in T2-value of 25.1 ms (+/-SD 3.5 ms) was found on T2-maps. The chondrocyte-specific genes aggrecan, collagen type 2, and sox9 were all affected by labeling, the two latter In a dose-dependent manner. VSOPs had no effect on proliferation. Conclusion: VSOP labeling of chondrocytes affected gene expression but not proliferation. The labeled chondrocytes could be recognized by MRI for 4 weeks without significant changes in the T2 relaxation time.