title: MR imaging features of gadofluorine-labeled matrix-associated stem cell implants in cartilage defects.
abstract: OBJECTIVE
  The purpose of our study was to assess the chondrogenic potential and the MR signal effects of GadofluorineM-Cy labeled matrix associated stem cell implants (MASI) in pig knee specimen.
  
  
  METHODS
  Human mesenchymal stem cells (hMSCs) were labeled with the micelle-based contrast agent GadofluorineM-Cy. Ferucarbotran-labeled hMSCs, non-labeled hMSCs and scaffold only served as controls. Chondrogenic differentiation was induced and gene expression and histologic evaluation were performed. The proportions of spindle-shaped vs. round cells of chondrogenic pellets were compared between experimental groups using the Fisher's exact test. Labeled and unlabeled hMSCs and chondrocytes in scaffolds were implanted into cartilage defects of porcine femoral condyles and underwent MR imaging with T1- and T2-weighted SE and GE sequences. Contrast-to-noise ratios (CNR) between implants and adjacent cartilage were determined and analyzed for significant differences between different experimental groups using the Kruskal-Wallis test. Significance was assigned for p<0.017, considering a Bonferroni correction for multiple comparisons.
  
  
  RESULTS
  Collagen type II gene expression levels were not significantly different between different groups (p>0.017). However, hMSC differentiation into chondrocytes was superior for unlabeled and GadofluorineM-Cy-labeled cells compared with Ferucarbotran-labeled cells, as evidenced by a significantly higher proportion of spindle cells in chondrogenic pellets (p<0.05). GadofluorineM-Cy-labeled hMSCs and chondrocytes showed a positive signal effect on T1-weighted images and a negative signal effect on T2-weighted images while Ferucarbotran-labeled cells provided a negative signal effect on all sequences. CNR data for both GadofluorineM-Cy-labeled and Ferucarbotran-labeled hMSCs were significantly different compared to unlabeled control cells on T1-weighted SE and T2*-weighted MR images (p<0.017).
  
  
  CONCLUSIONS
  hMSCs can be labeled by simple incubation with GadofluorineM-Cy. The labeled cells provide significant MR signal effects and less impaired chondrogenesis compared to Ferucarbotran-labeled hMSCs. Thus, GadoflurineM-Cy might represent an alternative MR cell marker to Ferucarbotran, which is not distributed any more in Europe or North America.
authors.affiliation: Department of Radiology, Stanford University, Stanford, California, United States of America. heiked@stanford.edu
authors.forename: Hossein
authors.initials: H
authors.lastname: Nejadnik
authors.forename: Tobias D
authors.initials: TD
authors.lastname: Henning
authors.forename: Thuy
authors.initials: T
authors.lastname: Do
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Sutton
authors.forename: Frederick
authors.initials: F
authors.lastname: Baehner
authors.forename: Andrew
authors.initials: A
authors.lastname: Horvai
authors.forename: Barbara
authors.initials: B
authors.lastname: Sennino
authors.forename: Donald
authors.initials: D
authors.lastname: McDonald
authors.forename: Reinhard
authors.initials: R
authors.lastname: Meier
authors.forename: Bernd
authors.initials: B
authors.lastname: Misselwitz
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Link
authors.forename: Heike E
authors.initials: HE
authors.lastname: Daldrup-Link
mesh_terms: D000818:Animals; D002358:Cartilage, Articular / Q000166:cytology* / Q000502:physiology; D019902:Chondrocytes / Q000166:cytology*; D020219:Chondrogenesis / Q000502:physiology*; D003287:Contrast Media; D006801:Humans; D007719:Knee Joint / Q000166:cytology* / Q000502:physiology; D008279:Magnetic Resonance Imaging; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D009942:Organometallic Compounds; D013552:Swine; D054457:Tissue Scaffolds
chemical_list: D003287:Contrast Media; D009942:Organometallic Compounds; C477144:gadofluorine