Abstract
ObjectivesThe 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.Materials and MethodsHuman 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.ResultsCollagen 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).ConclusionhMSCs 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.
Highlights
New cell-based therapies for osteoarthritis and rheumatoid arthritis are currently being developed with the goal of providing regeneration of bone and cartilage
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)
Contrast-to-noise ratios (CNR) data for both GadofluorineM-Cy-labeled and Ferucarbotran-labeled Human mesenchymal stem cells (hMSCs) were significantly different compared to unlabeled control cells on T1-weighted spin echo (SE) and T2*-weighted MR images (p,0.017)
Summary
New cell-based therapies for osteoarthritis and rheumatoid arthritis are currently being developed with the goal of providing regeneration of bone and cartilage. Chondrocyte implants for cartilage regeneration have entered clinical practice [4]. These implants partly tend to form fibrocartilage instead of hyaline cartilage [5] and recovery is slower compared with osteochondral autograft implantation (OAT) [6]. HMSCs are well characterised autologous cells, which are obtained by a bone marrow aspirate and efficiently expanded in vitro [7]. They may differentiate towards osteocytes and chondrocytes and, thereby, may regenerate destructed joint components [8]. The differentiation outcomes of hMSCs embedded in biomaterials and in the context of arthritic joints remains to be studied [7,8,9,10,11]
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