Effects of iron oxide incorporation for long term cell tracking on MSC differentiation in vitro and in vivo

Biochem Biophys Res Commun. 2008 May 16;369(4):1076-81. doi: 10.1016/j.bbrc.2008.02.159. Epub 2008 Mar 10.


Successful cell therapy will depend on the ability to monitor transplanted cells. With cell labeling, it is important to demonstrate efficient long term labeling without deleterious effects on cell phenotype and differentiation capacity. We demonstrate long term (7 weeks) retention of superparamagnetic iron oxide particles (SPIO) by mesenchymal stem cells (MSCs) in vivo, detectable by MRI. In vitro, multilineage differentiation (osteogenic, chondrogenic and adipogenic) was demonstrated by histological evaluation and molecular analysis in SPIO labeled and unlabeled cells. Gene expression levels were comaparable to unlabeled controls in adipogenic and chondrogenic conditions however not in the osteogenic condition. MSCs seeded into a scaffold for 21 days and implanted subcutaneously into nude mice for 4 weeks, showed profoundly altered phenotypes in SPIO labeled samples compared to implanted unlabeled control scaffolds, indicating chondrogenic differentiation. This study demonstrates long term MSC traceability using SPIO and MRI, uninhibited multilineage MSC differentiation following SPIO labeling, though with subtle but significant phenotypical alterations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipogenesis / drug effects
  • Adipogenesis / genetics
  • Animals
  • Cell Differentiation / drug effects*
  • Cell Differentiation / genetics
  • Cell Lineage / drug effects
  • Cell Lineage / genetics
  • Chondrogenesis / drug effects
  • Chondrogenesis / genetics
  • Contrast Media / analysis
  • Contrast Media / chemistry
  • Contrast Media / toxicity*
  • Dextrans
  • Ferrosoferric Oxide
  • Gene Expression
  • Humans
  • Iron / analysis
  • Iron / chemistry
  • Iron / toxicity*
  • Magnetic Resonance Spectroscopy
  • Magnetite Nanoparticles
  • Mesenchymal Stem Cells / chemistry
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / drug effects*
  • Mice
  • Mice, Nude
  • Osteogenesis / drug effects
  • Osteogenesis / genetics
  • Oxides / analysis
  • Oxides / chemistry
  • Oxides / toxicity*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Staining and Labeling / methods*


  • Contrast Media
  • Dextrans
  • Magnetite Nanoparticles
  • Oxides
  • Iron
  • ferumoxides
  • Ferrosoferric Oxide