A and B, Macroscopic (A) and histologic (B) evaluation of representative joints from rats injected with muscle-derived stem cells (MDSCs) transduced with soluble Flt-1 (sFlt-1) and bone morphogenetic protein 4 (BMP-4 [B4]) (sFlt-1/BMP-4–MDSC), MDSCs transduced with vascular endothelial growth factor (VEGF) and BMP-4 (VEGF/BMP-4–MDSC), MDSCs transduced with BMP-4 alone (BMP-4–MDSC), nontransduced MDSCs (MDSC), or phosphate buffered saline (PBS) alone, 4 and 12 weeks after transplantation. Four weeks after transplantation, the sFlt-1/BMP-4–MDSC and BMP-4–MDSC groups macroscopically and histologically showed smooth joint surface with well-repaired articular cartilage and Safranin O–positive hyaline-like cartilage (red staining in B). However, the other groups showed marked arthritic progression, synovial hypertrophy, and osteophyte formation (arrows). Twelve weeks after transplantation, although the sFlt-1/BMP-4–MDSC group still showed well-repaired articular cartilage, the other groups exhibited more severe arthritis compared with 4 weeks. (Original magnification  100.) C, Semiquantitative histologic scores for all groups, 4 and 12 weeks following transplantation. The sFlt-1/BMP-4–MDSC group had the lowest (best) scores of all groups. Bars show the mean and SEM.   P   0.05 versus all other groups;   P   0.05 versus the VEGF/BMP-4–MDSC, MDSC, and PBS groups.