Efficacy and Safety of Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells in Anterior Cruciate Ligament Reconstruction of a Rabbit Model: New Strategy to Enhance Tendon Graft Healing

Purpose: To investigate whether non-autologous transplantation of human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) could be integrated safely at the bone-tendon junction without immune rejection and could enhance bone-tendon healing effectively during anterior cruciate ligament (ACL) reconstruction in an animal model. Methods: ACL reconstructions using hamstring tendons were performed in 30 adult rabbits. The bone tunnels were treated with hUCB-MSCs or were untreated. The specimens were harvested at 4, 8, and 12 weeks. We performed a gross examination of the knee joint; a histologic assessment using H&E staining, as well as immunohistochemical staining, for type II collagen; and an evaluation of bone tunnel widening using micro-computed tomography. Results: No evidence of immune rejection was detected. Tendon-bone healing through Sharpey-like fibers was noticed around tendon grafts at 12 weeks in the control group. A smooth transition from bone to tendon through broad fibrocartilage formation was identified in the treatment group, and the interface zone showed abundant type II collagen production on immunohistochemical staining. Histologic scores for bone-tendon healing were significantly higher in the treatment group at all time points (P < .001). Micro-computed tomography at 12 weeks showed a significantly smaller tibial (P = .029) and femoral (P = .033) bone tunnel enlargement in the treated group than in the control group. Conclusions: Non-autologous transplantation of hUCB-MSCs was applied in ACL reconstruction without early immune rejection. There was enhanced tendon-bone healing through broad fibrocartilage formation with higher histologic scores and decreased femoral and tibial tunnel widening compared with the control group (79.2% and 80%, respectively, of the control group tunnel area at 12 weeks). Clinical Relevance: Non-autologous transplantation of hUCB-MSCs has therapeutic potential in promoting tendon-to-bone healing after ACL reconstruction. Further study in the human model is warranted.