Tracer Study With MRI On Hypoxia-preconditioning Bone Marrow Mesenchymal Cells To Repair Articular Cartilage Defects

Background and Objective:Due to the hypovascular biostructure and poor self-repairing capacity,articular cartilage defects are difficult to repair.Currently,bone marrow mesenchymal stem cells(BM-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 because of low transformation efficiency.In the present study,different external and internal bio-conditions were applied to regulate the biological behavior of cells.Methods:Superparamagnetic iron oxide nanoparticles(SPIONs)were firstly constructed and were applied to label BM-MSCs under different oxygen environments.The impact of hypoxia precondition and SPIONs-based nano-effect on the cell viability,cell cycle,apoptosis and the stem cell differetiations were measured by flow cytometric analysis.Moreover,the qRT-PCR and WB analysis were performed to study the change of gene and protein level.Transwell assay and wound-healing assay detected the BM-MSCs'migration capability.Then,the hypoxia-precondition BM-MSCs were transplanted into the rat models with articular cartilage disease and the treatment effect was evaluated by MRI scan and histological analysis.Results:1.stPEI/SPIONs were successfully synthesized with suitable diameter,size and charge,and the relaxation rate of SPIONs was high.2.Under the normoxia or hypoxia environment,BM-MSCs were labeled at the rate of 99%with 5?g/ml SPIONs,and their viability and sternness markers were not influenced.3.The hypoxia environment could remit the acculated effect of BM-MSCs cell cycly caused by SPIONs.4.SPIONs would not result in BM-MSCs' apoptosis but higher ROS production,and hypoxia precondition could reduce the ROS production.5.SPIONs would not affect the multi-directional differentiation of BM-MSCs.Hypoixa induced BM-MSCs to express higher chondrocyte markers.6.Synergistic effect of hypoxia environment and SPIONs enhanced the migration capability.7.Hypoxia-precondition BM-MSCs chould trancform more efficiently to chondrocyte with an excellent repairing in rat model of articular cartilage defect.Conclusion:The synergistic effect of hypoxia-precondition and SPIONs based cellular iron source is a "safe and gentle way" to improve the cell migration and facilitates chondrogenic differentiation.