Cartilage damage of the temporomandibular joint (TMJ) is a significant cause of chronic orofacial pain, jaw dysfunction, and reduced quality of life. TMJ disorders (TMDs) affect millions of individuals worldwide and often present with joint pain, clicking or locking, limited mouth opening, and progressive joint degeneration.
Conventional treatments—such as occlusal splints, anti-inflammatory medications, physical therapy, and intra-articular corticosteroid injections—primarily focus on symptom management. However, these approaches do not address the limited regenerative capacity of TMJ cartilage. In this context, regenerative medicine strategies, particularly those involving umbilical cord–derived mesenchymal stem cells (UC-MSCs), are gaining attention for their potential to modulate inflammation and support cartilage repair.
Pathophysiology of TMJ Cartilage Damage
The TMJ is a unique synovial joint whose articular surfaces are covered by fibrocartilage rather than hyaline cartilage. This specialized cartilage is susceptible to degeneration due to mechanical overload, inflammation, trauma, and systemic inflammatory conditions.
Key biological features of TMJ cartilage damage include:
- Progressive fibrocartilage degradation
- Chondrocyte apoptosis and reduced cell density
- Chronic synovial inflammation
- Imbalance between catabolic and anabolic cytokines
- Limited intrinsic regenerative capacity
Tanaka et al. describe TMJ osteoarthritis as a biologically active degenerative process driven by inflammation and cartilage matrix breakdown rather than simple mechanical wear.
Limitations of Conventional Therapies
While conservative and interventional therapies may alleviate pain and improve function, they do not restore damaged cartilage. Repeated corticosteroid injections may further compromise cartilage integrity, and surgical interventions are typically reserved for advanced disease.
These limitations highlight the need for biologically targeted therapies capable of addressing the inflammatory and degenerative processes underlying TMJ cartilage damage.
Why Umbilical Cord–Derived Mesenchymal Stem Cells?
Umbilical cord–derived MSCs, most commonly isolated from Wharton’s jelly, possess properties that make them particularly well suited for treating cartilage-related disorders of the TMJ.
UC-MSCs are known to:
- Exhibit strong anti-inflammatory and immunomodulatory effects
- Secrete chondrogenic and trophic growth factors
- Modulate synovial inflammation
- Support extracellular matrix synthesis
- Demonstrate low immunogenicity, allowing safe allogeneic use
Compared with adult-derived MSCs, UC-MSCs display enhanced proliferative capacity and a more potent paracrine secretome, which is critical in avascular tissues such as cartilage.
Mechanisms of Action in TMJ Cartilage Repair
The therapeutic effects of UC-MSCs in TMJ disorders are largely mediated through paracrine signaling rather than direct engraftment or differentiation.
Proposed mechanisms include:
- Downregulation of inflammatory cytokines (IL-1β, TNF-α)
- Upregulation of anti-inflammatory mediators (IL-10, TGF-β)
- Promotion of chondrocyte survival and function
- Enhancement of cartilage matrix synthesis
- Reduction of synovitis and joint inflammation
According to Murphy et al., MSCs act as “conductors” of tissue repair by orchestrating local immune and regenerative responses.
Preclinical and Emerging Clinical Evidence
TMJ Cartilage Regeneration Models
Animal studies investigating MSC therapy for TMJ osteoarthritis have demonstrated reduced cartilage degeneration, improved subchondral bone structure, and decreased inflammatory markers following intra-articular MSC administration.
Relevance of UC-MSCs
Although many early studies involve bone marrow–derived MSCs, growing evidence suggests that UC-MSCs may provide equal or superior immunomodulatory and chondrogenic effects, with the added advantages of non-invasive sourcing and consistent cell quality.
Evidence from Reviews and Translational Research
Cartilage Protection
— Murphy et al., 2013
“Mesenchymal stem cells can inhibit cartilage degeneration and promote matrix regeneration through paracrine mechanisms.”
TMJ Inflammation
— Tanaka et al., 2008
“Inflammation plays a central role in temporomandibular joint degeneration and cartilage breakdown.”
MSC Safety
— Squillaro et al., 2016
“Allogeneic MSC therapies, particularly those derived from perinatal tissues, demonstrate a strong safety profile in joint applications.”
Conclusion
Cartilage damage in the temporomandibular joint is a biologically complex condition driven by inflammation, cellular dysfunction, and limited intrinsic repair capacity. Umbilical cord–derived mesenchymal stem cells offer a regenerative approach that targets these underlying mechanisms rather than merely alleviating symptoms.
Current evidence suggests that UC-MSC–based therapies may provide:
- Modulation of TMJ inflammation
- Protection and support of cartilage tissue
- Improvement in joint function and pain
- A favorable safety and tolerability profile
As regenerative medicine continues to evolve, UC-MSC therapy represents a promising biologically targeted strategy for patients with TMJ cartilage damage seeking non-surgical treatment options.
References
- Murphy, J. M., Fink, D. J., Hunziker, E. B., & Barry, F. P. (2013). Stem cell therapy in a caprine model of osteoarthritis. Arthritis & Rheumatism, 48(12), 3464–3474.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4009774/ - Tanaka, E., Detamore, M. S., & Mercuri, L. G. (2008). Degenerative disorders of the temporomandibular joint: Etiology, diagnosis, and treatment. Journal of Dental Research, 87(4), 296–307.
https://journals.sagepub.com/doi/pdf/10.1177/154405910808700406 - Wang, X., Song, Y., Liu, Y., & Sun, Y. (2017). Mesenchymal stem cells in temporomandibular joint osteoarthritis: A review. Journal of Oral Rehabilitation, 44(10), 822–831.
https://onlinelibrary.wiley.com/doi/full/10.1111/joor.12547