Chondrocyte gene expression is affected by very small iron oxide particles-labeling in long-term in vitro MRI
Casper Bindzus Foldager1, Michael Pedersen, Steffen Ringgaard
1Orthopedic Research Laboratory, Aarhus University Hospital, NBG, Aarhus, Denmark. foldager@ki.au.dk
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.
