The Regulation of Mesenchymal Stem Cell Therapy Through Magnetic Resonance Imaging Agents-Based Cellular Condition and Oxygen Environment

Repairing articular cartilage defects is difficult due to the hypovascular biostructure and poor self-repairing capacity of articular cartilage. Currently, mesenchymal stem cells (MSCs) with excellent differentiation potential are considered as a promising biological approach for cartilage regeneration. The effect, however, remains far from satisfactory for clinical applications owing to the main drawbacks of tracking the retention of cells and a low differentiation efficiency. As known, the nanoparticles with superparamagnetic properties has been used to monitor the MSCs in vivo through magnetic resonance imaging (MRI) in clinical application. In this study, different external and internal bio-conditions were applied to regulate the biological behavior of cells. Here, intracellular MRI contrast agents, superparamagnetic iron oxide nanocrystals (SPIONs), and a hypoxic culture environment were found to exert synergistic effects on gene and protein expression, and the cell viability, cell cycle, apoptosis, reactive oxygen species and the stem cell differentiations were measured. The levels of chondrogenic and migrant markers (including collagen II, collagen X, aggrecan, SOX9, MMPs and CXCR4) increased, triggering directional differentiation and enhancing cell migration to the inflammatory site. Moreover, SPION-labeled hypoxia-preconditioned MSCs were found without reactive oxygen species generation and transplanted into rat models with articular cartilage disorders. Interestingly, MRI and histological identification confirmed that new cartilage-like tissue was regenerated and that defects were repaired, and this method is more efficient for cartilage regeneration than SPION-labeled normoxia MSCs. The synergistic effect of hypoxia-precondition and SPIONs based cellular iron source could improve the cell migration and facilitate chondrogenic differentiation.