Intra-articular injection of mesenchymal stromal cells in partially torn anterior cruciate ligaments in a rat model.

Abstract

The purpose of this study was to biomechanically and histologically evaluate whether intra-articularly injected mesenchymal stromal cells can accelerate the healing of a partially torn anterior cruciate ligament (ACL). Ninety-eight 12-week-old male Sprague-Dawley rats were studied. The right ACL was partially transected, and a sham operation was performed on the left knee. Mesenchymal stromal cells obtained from bone marrow of green fluorescent protein (GFP) transgenic Sprague-Dawley rats were cultured for 2 weeks in medium. In the MSC(+) group, 1 x 10(6) cells were suspended in phosphate-buffered saline solution and were injected into the right knee with the partially transected ACL. In the MSC(-) group, only phosphate-buffered saline solution was injected. Six animals from each group were evaluated histologically at 1, 2, 3, and 4 weeks after surgery, and they were evaluated biomechanically immediately after surgery (time zero) (n = 9) and also at 2 weeks (n = 11) and 4 weeks (n = 12) after surgery in both groups. For biomechanical testing, the ultimate failure load of a prepared femur-ACL-tibia complex was measured. We then compared the transected side with the sham side in each group. GFP luminescence was observed with a fluorescence microscope to detect whether the injected cells mobilized into the covered tissue. In the MSC(-) group the transected area retracted with increasing time, and the gap remained void of any tissues at all time points after surgery. In the MSC(+) group at 2 and 4 weeks after surgery, the transected area was covered with healing tissues in which GFP-positive cells were detected. Furthermore, the histologic score of the MSC(+) group was significantly better than that of the MSC(-) group. The ultimate failure load of the femur-ACL-tibia complex in the MSC(+) group was significantly higher than that in the MSC(-) group at 4 weeks after surgery. We conclude from our histologic and biomechanical measurements that injected mesenchymal stromal cells can accelerate the healing of partially torn ACLs. The intra-articular injection of mesenchymal stromal cells can be a viable option for treating partially torn knee ACLs.