Efficacy of Stem Cell Therapy for Tendon Graft Ligamentization After Anterior Cruciate Ligament Reconstruction: A Systematic Review

BACKGROUND: Sufficient intra-articular graft ligamentization enhances the biomechanical and biological properties of the femur-graft-tibia complex to ensure knee stability after anterior cruciate ligament (ACL) reconstruction using a tendon graft. It remains unclear whether stem cell therapy promotes tendon graft ligamentization. PURPOSE/HYPOTHESIS: The purpose of this study was to compare tendon graft ligamentization after primary ACL reconstruction with versus without stem cell therapy. It was hypothesized was that stem cell therapy would promote tendon graft ligamentization by enhancing the biomechanical and histological properties of the tendon graft after ACL reconstruction. STUDY DESIGN: Systematic review. METHODS: A systematic review was performed according to the guidelines outlined in the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement to identify controlled animal studies that compared tendon graft ligamentization outcomes after primary ACL reconstruction in groups with and without stem cell therapy. Biomechanical and histological outcomes were assessed. RESULTS: A total of 4 studies met the eligibility criteria and were included in this review. Bone marrow–derived mesenchymal stem cells were used in 3 studies, while tendon-derived stem cells were used in 1 study. An intra-articular injection was used to deliver conditioned medium and stem cells in 2 studies, while around-graft application was used to deliver bone marrow–derived mesenchymal stem cells in 2 studies. Stem cell therapy enhanced the biomechanical and histological properties of the tendon graft after ACL reconstruction. CONCLUSION: This review revealed that stem cell therapy is a promising technique that promotes graft ligamentization by enhancing the biomechanical and histological properties of the tendon graft after ACL reconstruction in animal models. There is a need for future preclinical studies aimed at evaluating the effect of stem cells on graft ligamentization and identifying the optimal method of intra-articular stem cell delivery.