Characterization of Anterior Cruciate Ligament–Derived Stem Cells (ACL-DSCs) in Anterior Cruciate Ligament Rupture: A Literature Review

Abstract

This review synthesizes current evidence on anterior cruciate ligament–derived stem/stromal cells (ACL-DSCs) as a potential autologous cell source for ligament regeneration. Narrative analysis of in vitro, animal, and early clinical studies highlights their consistent mesenchymal immunophenotype and a tissue-specific bias toward ligament lineage, with higher expression of master regulators such as SCX and MKX compared with bone marrow derived MSCs. Under tenogenic cues, ACL-DSCs demonstrate enhanced proliferation, extracellular matrix deposition, and secretion of trophic mediators, including IGF-1, that promote fibroblast proliferation, collagen synthesis, angiogenesis, and enthesis maturation. Collagen-based and biomimetic scaffolds further augment their regenerative potential, supporting ligament-like matrix formation and tendon-to-bone integration. Preclinical models report accelerated graft ligamentization and improved biomechanical outcomes, although translational progress remains constrained by heterogeneity in isolation and induction protocols, variability in outcome measures, limited human data, and undefined dosing or delivery strategies. ACL-DSCs therefore represent a promising, tissue-matched candidate for biologically informed ACL reconstruction, but standardization of protocols, harmonization of imaging and histologic endpoints, and adequately powered clinical trials are required to establish efficacy, safety, and long-term durability.