Clinical outcomes of stem cell-augmented anterior cruciate ligament reconstruction: A systematic review
Febyan Febyan, I Gusti Ngurah Wien Aryana, Jordaniel SetiabudiBackground and Aims:
Anterior cruciate ligament reconstruction (ACLR) is commonly performed to restore knee stability after anterior cruciate ligament injury. However, suboptimal graft healing and ligamentization may contribute to reconstruction failure. Mesenchymal stem cell (MSC)-based therapies have been proposed as biological adjuncts to improve graft integration and clinical outcomes after ACL reconstruction. This systematic review aimed to evaluate the clinical outcomes of stem cell-augmented ACL reconstruction compared with conventional ACL reconstruction.
Materials and Methods:
A systematic review was conducted in accordance with the PRISMA 2020 guidelines. Electronic databases, including PubMed, Scopus, Web of Science, and the Cochrane Library, were searched from database inception to December 2025. Eligible studies included randomized controlled trials, cohort studies, and case-control studies evaluating stem cell augmentation in ACLR with a relevant comparator. Data were extracted on study design, graft type, stem cell source, delivery method, follow-up duration, graft maturation, functional scores, pain outcomes, knee stability, and adverse events. Due to heterogeneity in intervention protocols and outcome measures, findings were synthesized qualitatively.
Results:
Four studies met the inclusion criteria, consisting of three randomized controlled trials and one non-randomized clinical trial. Stem cell sources included bone marrow-derived mesenchymal stem cells, adipose-derived stem cells, and human umbilical cord blood-derived mesenchymal stem cells. Delivery methods included intraoperative graft or tendon-bone interface application and postoperative intra-articular injection. Reported outcomes were heterogeneous. Some studies showed improvements in pain, symptoms, and selected imaging-based structural outcomes, whereas others demonstrated no significant benefit in graft maturation, functional scores, knee stability, tunnel enlargement, or arthroscopic findings compared with control groups. No major treatment-related safety concerns were reported in the included studies.
Conclusion:
Stem cell augmentation in ACLR appears feasible and generally safe, with potential biological benefits for graft healing and symptom improvement. However, current clinical evidence remains limited and heterogeneous, and consistent superiority over conventional ACL reconstruction has not been established. Further adequately powered, standardized clinical trials are required to determine the clinical value of stem cell augmentation in ACL reconstruction.