Systematic Review
Temporomandibular joint disorders (TMDs), particularly those involving degenerative cartilage changes and osteoarthritis, represent a significant clinical challenge due to the limited intrinsic regenerative capacity of fibrocartilaginous tissues. Stem cell–based therapies have emerged as a promising regenerative strategy aimed at modulating inflammation and promoting structural joint repair. This systematic review evaluated the current evidence regarding the therapeutic potential of mesenchymal stem/stromal cells (MSCs) and related cell-derived products for the treatment of temporomandibular joint (TMJ) disorders. A structured literature search was conducted in PubMed/MEDLINE and Google Scholar for studies published between January 2000 and December 2025, following PRISMA 2020 guidelines. Eligible studies included clinical trials, observational studies, case series, animal studies, and systematic reviews investigating stem cell–based interventions in TMJ pathology. A total of 26 studies met the inclusion criteria and were analyzed qualitatively. Preclinical studies consistently demonstrated anti-inflammatory, chondroprotective, and regenerative effects following intra-articular administration of MSCs or MSC-derived products. Clinical studies reported reductions in pain intensity and improvements in mandibular function, although methodological heterogeneity and limited sample sizes restricted the strength of conclusions. Emerging approaches involving extracellular vesicles and secretome-based therapies showed promising translational potential. Overall, stem cell–based therapies represent a biologically plausible and potentially effective treatment modality for TMJ disorders; however, high quality randomized controlled trials with standardized outcome measures are required to confirm their long-term efficacy and safety.
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