Blocking VEGF as a potential approach to improve cartilage healing after osteoarthritis.

Mouse MDSCs were obtained from three-week old male wild type mice using a modified preplate technique. The effect of VEGF on chondrogenesis using a chemical induced OA model in 10-week-old female nude rats was tested using genetically engineered MDSCs. In this model, MDSCs, transduced with a retroviral vector to express BMP4-GFP (BMP4-MDSCs), were co-injected in the joint capsule with MDSCs transduced to express either VEGF-LacZ (VEGFMDSCs) or sFlt1-LacZ (a VEGF antagonist) (sFlt1MDSCs) to test gainand loss-of VEGF function (5 x 10 cells total). The effect of VEGF and blocking VEGF on the in vitro chondrogenic ability of MDSCs was also tested using a mixed pellet co-culture system followed by gross and histological analyses (transduced-MDSCs and OA chondrocytes) (2 x 10 cells total).