Effect of transplanted mesenchymal stem cell number on the prevention of cartilage degeneration and pain reduction in a posttraumatic osteoarthritis rat model

Mesenchymal stem cells (MSCs) transplantation therapy is considered an alternative therapy to prevent posttraumatic osteoarthritis (PTOA). However, consensus as to the sufficient number of MSCs for the prevention of PTOA is lacking. The purpose of this study was to determine the sufficient number of MSCs to achieve PTOA prevention and the reduction in pain after anterior cruciate ligament transection (ACLT). Eight-week-old male Wistar rats were used. ACLT was conducted in the knee joint as a PTOA model. According to the species-specific knee joint volume, 104 MSCs in rats are equivalent to 3 × 107 MSCs in humans, which was clinically prepared. MSCs (104, 105, or 106 cells) or phosphate-buffered saline were injected into the knee joint at 1, 2, and 3 weeks after ACLT. Histological examinations were performed at 12 weeks after ACLT. The weight-bearing distribution improvement ratio was calculated as an assessment of pain until 12 weeks after ACLT. Histological evaluations showed that all the MSCs groups except for 104 MSCs group in femur were significantly improved compared to the control group at 12 weeks after ACLT. The weight-bearing distribution in the 104 and 105 MSCs groups at 12 weeks after ACLT and in the 106 MSCs group at 6, 8, 10, and 12 weeks after ACLT were significantly higher than those of the control group. A clinically feasible number of MSCs was found to reduce the articular cartilage degeneration and to decrease pain in the PTOA model. Increasing numbers of the cells further protected the articular cartilage against degeneration.