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 μg/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 μg/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. J. Magn. Reson. Imaging 2011;33:724–730. © 2011 Wiley‐Liss, Inc.