title: Chondrocyte gene expression is affected by very small iron oxide particles-labeling in long-term in vitro MRI tracking.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Orthopedic Research Laboratory, Aarhus University Hospital, NBG, Aarhus, Denmark. foldager@ki.au.dk
authors.forename: Casper Bindzus
authors.initials: CB
authors.lastname: Foldager
authors.forename: Michael
authors.initials: M
authors.lastname: Pedersen
authors.forename: Steffen
authors.initials: S
authors.lastname: Ringgaard
authors.forename: Cody
authors.initials: C
authors.lastname: Bünger
authors.forename: Martin
authors.initials: M
authors.lastname: Lind
mesh_terms: D001706:Biopsy; D002356:Cartilage / Q000378:metabolism; D049109:Cell Proliferation; D019902:Chondrocytes / Q000166:cytology*; D003287:Contrast Media / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005269:Femur / Q000473:pathology; D005290:Ferric Compounds / Q000737:chemistry*; D005786:Gene Expression Regulation; D006801:Humans; D066298:In Vitro Techniques; D008279:Magnetic Resonance Imaging / Q000379:methods*; D012313:RNA / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors
chemical_list: D003287:Contrast Media; D005290:Ferric Compounds; C000499:ferric oxide; D012313:RNA