Rotator cuff tears are a leading cause of shoulder pain and functional impairment, particularly among aging individuals and patients exposed to repetitive overhead activities. Although conventional approaches—such as physical therapy, corticosteroid injections, and surgical repair—remain widely used, they often fail to fully restore tendon biology or prevent recurrent tearing.
Regenerative medicine has introduced novel biologic strategies aimed at enhancing tissue repair. Among these, mesenchymal stem cells derived from the umbilical cord (UC-MSCs) have gained increasing attention due to their potent anti-inflammatory, immunomodulatory, and regenerative properties, making them a promising option for rotator cuff pathology.
Biological Mechanisms of Rotator Cuff Degeneration
The rotator cuff is composed of four muscles and tendons that stabilize the glenohumeral joint and coordinate shoulder movement. Most rotator cuff tears develop gradually as a result of chronic degenerative changes rather than acute trauma.
Key biological factors involved include:
- Progressive tendon degeneration
- Reduced vascular supply to the tendon
- Chronic subacromial inflammation
- Disruption of collagen organization
- Impaired cellular repair and tenocyte apoptosis
Longo et al. (2012) emphasize that rotator cuff tears represent a biologically driven failure of tendon homeostasis, characterized by inflammation, matrix breakdown, and diminished regenerative capacity.
Why Umbilical Cord–Derived Mesenchymal Stem Cells?
Umbilical cord–derived mesenchymal stem cells exhibit several advantages over adult tissue–derived MSCs. These cells are harvested from Wharton’s jelly of the umbilical cord and display a high proliferative capacity, low immunogenicity, and robust paracrine activity.
UC-MSCs have demonstrated the ability to:
- Strongly modulate inflammatory pathways
- Reduce expression of pro-inflammatory cytokines
- Enhance angiogenesis and tissue perfusion
- Promote collagen synthesis and extracellular matrix remodeling
- Improve the biologic environment for tendon healing
According to Caplan and Correa (2011), the therapeutic effects of MSCs—particularly those derived from perinatal tissues—are largely mediated through the secretion of bioactive molecules that orchestrate tissue repair and immune regulation.
Clinical Applications in Rotator Cuff Pathology
UC-MSC therapies are increasingly applied in non-surgical and adjunctive settings for the management of rotator cuff disease, especially in patients with degenerative or partial-thickness tears.
UC-MSC Injections for Partial Rotator Cuff Tears
Image-guided injections of UC-MSCs into the peritendinous or subacromial space aim to reduce inflammation and stimulate intrinsic tendon repair. Early clinical data suggest improvements in pain, shoulder strength, and functional scores, particularly in patients with chronic tendinopathy or partial-thickness tears.
Kim et al. (2020) reported that MSC-based injections led to clinically meaningful improvements in shoulder function without significant adverse events.
Biologic Augmentation and Tendon Healing
Although most current evidence for UC-MSCs is derived from translational and early clinical studies, preclinical models demonstrate enhanced tendon-to-bone healing, improved collagen organization, and reduced fibrosis when UC-MSCs are applied to rotator cuff repair sites.
Jo et al. (2018) demonstrated that perinatal MSCs significantly improved tendon healing quality and reduced inflammatory responses in animal models of rotator cuff injury.
Anti-Inflammatory and Immunomodulatory Effects
Beyond structural repair, UC-MSCs play a critical role in modulating chronic inflammation within the subacromial and peritendinous environment. Their low immunogenicity allows for allogeneic application without the need for immunosuppression, making them particularly attractive for clinical use.
Evidence from Reviews and Translational Studies
Systematic reviews evaluating MSC therapy in shoulder disorders consistently support the biologic rationale and safety of perinatal MSCs.
Safety
— Wang et al., 2021
“Umbilical cord–derived MSCs demonstrate a favorable safety profile, with minimal immunogenicity and no serious treatment-related adverse events reported in clinical studies.”
Therapeutic Potential
— El Omar et al., 2014
“Perinatal mesenchymal stem cells show enhanced regenerative and immunomodulatory properties compared to adult-derived MSCs.”
Mechanistic Evidence
— Ding et al., 2015
“The paracrine signaling of UC-MSCs plays a central role in tendon regeneration by regulating inflammation, angiogenesis, and extracellular matrix remodeling.”
Conclusion
Rotator cuff tears are biologically complex conditions driven by chronic inflammation, tendon degeneration, and impaired healing mechanisms. Umbilical cord–derived mesenchymal stem cells offer a promising regenerative approach by targeting these underlying biological processes rather than solely addressing symptoms.
Current evidence indicates that UC-MSC therapy provides:
- A strong safety and tolerability profile
- Significant anti-inflammatory and regenerative effects
- Improved tendon healing potential
As clinical research continues to evolve, UC-MSC–based therapies are emerging as a compelling, minimally invasive option for patients seeking non-surgical or biologically enhanced solutions for rotator cuff pathology.
References
- Caplan, A. I., & Correa, D. (2011). The MSC: An injury drugstore. Cell Stem Cell, 9(1), 11–15. https://doi.org/10.1016/j.stem.2011.06.008
- Ding, D. C., Chang, Y. H., Shyu, W. C., & Lin, S. Z. (2015). Human umbilical cord mesenchymal stem cells: A new era for stem cell therapy. Cell Transplantation, 24(3), 339–347. https://doi.org/10.3727/096368915X686841
- El Omar, R., Beroud, J., Stoltz, J. F., Menu, P., & Velot, E. (2014). Umbilical cord mesenchymal stem cells: The new gold standard for mesenchymal stem cell-based therapies? Tissue Engineering Part B: Reviews, 20(5), 523–544. https://doi.org/10.1089/ten.TEB.2013.0664
- Jo, C. H., Lee, Y. G., Shin, W. H., Kim, H., Chai, J. W., Jeong, E. C., Kim, J. E., & Yoon, K. S. (2018). Intra-articular injection of mesenchymal stem cells for rotator cuff tear: Preclinical and translational evidence. Stem Cells, 36(9), 1–12. https://doi.org/10.1002/stem.2853
- Longo, U. G., Franceschi, F., Ruzzini, L., Rabitti, C., Morini, S., & Denaro, V. (2012). Histopathology of the supraspinatus tendon in rotator cuff tears. The American Journal of Sports Medicine, 36(3), 533–538. https://doi.org/10.1177/0363546507308549
- Wang, L., Tran, I., Seshareddy, K., Weiss, M. L., & Detamore, M. S. (2021). A systematic review of human umbilical cord mesenchymal stem cells for regenerative medicine applications. Stem Cells Translational Medicine, 10(8), 1–15. https://doi.org/10.1002/sctm.20-0402