Local Administration of Autologous Synovium-Derived Cells Improve the Structural Properties of Anterior Cruciate Ligament Autograft Reconstruction in Sheep

Abstract

Background: The structural properties of a tendon autograft deteriorate during the remodeling phase after anterior cruciate ligament (ACL) reconstruction.

Hypothesis: A local application of autologous synovium-derived cells cultured in medium supplemented with transforming growth factor β (TGFβ) may inhibit the deterioration of structural properties of the tendon graft after ACL reconstruction.

Study Design: Controlled laboratory study.

Methods: Fifty-two mature sheep were used. In each animal, the right knee underwent ACL reconstruction using the semitendinosus tendon autograft; then, the animals were divided into 5 groups of 10. No additional treatments were applied in group 1, whereas fibrin sealant was applied around the graft in group 2. In group 3, autologous synovium-derived cells cultured in standard medium were applied around the graft with fibrin sealant, whereas autologous synovium-derived cells cultured in TGFβ-supplemented medium were applied with fibrin sealant in group 4. In group 5, fibrin sealant containing 20 ng of TGFβ was applied around the graft. Each animal was sacrificed at 12 weeks after the surgery. In each group, 7 and 3 sheep were used for biomechanical and histologic evaluations, respectively. The remaining 2 sheep were used to confirm whether the applied cells infiltrated the graft at 1 week after surgery.

Results: Confocal microscope observations showed that the applied cells that were labeled before implantation infiltrated into the superficial portion of the graft at 1 week. Biomechanically, the maximum load and the stiffness of groups 4 and 5 were significantly greater than those of groups 1, 2, and 3. Histologically, necrotic lesions were observed in the core portion of the midsubstance in groups 1 and 2. In groups 3, 4, and 5, no necrotic lesions were found in the midsubstance.

Conclusion: A local application of autologous synovium-derived cells cultured in TGFβ-supplemented medium or a fibrin sealant containing TGFβ significantly inhibits the natural deterioration of the structural properties of the tendon graft after ACL reconstruction.

Clinical Relevance: Administration of autologous synovium-derived cells cultured in TGFβ-supplemented medium or TGFβ and fibrin glue alone can be a potential cell-based therapy to prevent graft deterioration after transplantation or accelerate mechanical restoration of the deteriorated graft.