Labeling Human Mesenchymal Stem Cells with Fluorescent Contrast Agents: the Biological Impact

This study aims to determine the effect of human mesenchymal stem cell (hMSC) labeling with the fluorescent dye DiD and the iron oxide nanoparticle ferucarbotran on chondrogenesis. hMSCs were labeled with DiD alone or with DiD and ferucarbotran (DiD/ferucarbotran). hMSCs underwent confocal microscopy, optical imaging (OI), and magnetic resonance (MR) imaging. Chondrogenesis was induced by transforming growth factor-b and confirmed by histopathology and glycosaminoglycan (GAG) production. Data of labeled and unlabeled hMSCs were compared with a t test. Cellular uptake of DiD and ferucarbotran was confirmed with confocal microscopy. DiD labeling caused a significant fluorescence on OI, and ferucarbotran labeling caused a significant T2* effect on MR images. Compared to nonlabeled controls, progenies of labeled MSCs exhibited similar chondrocyte morphology after chondrogenic differentiation, but the labeled cells demonstrated significantly reduced GAG production (p < 0.05). DiD and DiD/ferucarbotran labeling of hMSC does not interfere with cell viability or morphologic differentiation into chondrocytes, but labeled cells exhibit significantly less GAG production compared to unlabeled cells.