Advancements in Rotator Cuff Injury Treatment: Exploring the Role of Mesenchymal Stem Cell Therapy

Understanding the Rotator Cuff

The rotator cuff is a group of four small muscles and their tendons in your shoulder that work together to keep the shoulder stable and allow it to move smoothly. These muscles act as the "support team" for the shoulder joint, helping to lift and rotate the arm in various directions. Each muscle attaches from the shoulder blade to the top of the arm bone, forming a "cuff" around the joint.

Role in Everyday Activities

The rotator cuff is essential for many daily tasks, such as reaching, lifting, and even throwing. However, because it bears a lot of stress and is involved in constant movement, the rotator cuff is prone to injuries, especially with age.

The Impact and Risk Factors for Rotator Cuff Injuries

Rotator cuff injuries are among the leading causes of shoulder pain and functional limitations worldwide, impacting over 50% of people aged 60 and older. In the UK alone, approximately 2.4% of patients report shoulder issues in primary care, with 30-70% of these cases involving rotator cuff problems. (Hao-Nan Wang, Xiao Rong, Lu-Ming Yang et Al. 2022)

Key Risk Factors

Risk factors for rotator cuff injuries include:

- Aging

- Obesity

- Smoking

- Diabetes

- Genetics

- Specific work or sports activities that place additional stress on the shoulder

Age-related wear remains the primary factor, as the rotator cuff’s structure weakens over time, making injuries more likely.

Types of Rotator Cuff Injuries and Standard Treatments

Rotator cuff issues typically start with tendinopathy and may progress to partial or complete tears, causing significant pain and restricted mobility.

Conservative and Surgical Treatment Approaches

- Conservative treatments: Physiotherapy is generally the first line of treatment, especially for early cases of tendinopathy.

- Surgical options: Advanced injuries may require surgery, despite the considerable risk of non-healing and re-tearing. Studies indicate a re-tear rate as high as 38.1% after two years for double-row repairs, highlighting the need for improved regenerative approaches.

Challenges in Surgery: Fatty Infiltration and Muscle Atrophy

Fatty infiltration and muscle atrophy often complicate surgical recovery, leading to weaker outcomes and a higher likelihood of re-tears. Fatty degeneration, especially in the infraspinatus and subscapularis muscles, is a significant factor in re-tears post-surgery. The exact cellular cause of this fatty infiltration remains uncertain. (Ranjan Gupta, MDa, Rohan Rao, BSa, Tyler R. Johnston, MD et Al. 2021)

Regenerative Potential of Stem Cells in Rotator Cuff Healing

Mesenchymal stem cells offer unique regenerative capabilities (Zetao Wanga, Youguo Liao, Canlong Wang et. Al 2023), being able to multiply, renew, and transform into various cell types. They support healing by:

1. Growing into tissue of mesodermal origin

2. Releasing signaling factors and extracellular vesicles

3. Interacting with other mesenchymal and immune cells through apoptotic processes

In tendinopathy, mesenchymal stem cells release extracellular vesicles that regulate crucial biological processes.

Promising Research: Mesenchymal Stem Cells as an Alternative to Surgery

Clinical Evidence

Emerging studies support mesenchymal stem cell therapies as a potential alternative to traditional rotator cuff surgeries, which are often associated with re-tears and limited recovery. Injecting mesenchymal stem cells from bone marrow or adipose tissue has shown promise in enhancing pain relief, functional recovery, and lowering re-tear rates. (Seyed Peyman Mirghaderi, Zahra Valizadeh, Kimia Shadman et Al. 2022).

Notable studies:

    - A study by Kim YS found that while pain and motion improvements were similar, patients receiving mesenchymal stem cells had a lower re-tear rate (14.3% vs. 28.5%) on MRI.

    - Another study by Kim SJ observed improvements in pain and function among patients who received mesenchymal stem cells injections, even if the tear size remained unchanged.

Animal Studies

Animal model studies reveal that mesenchymal stem cells can strengthen tissue and improve cartilage formation. Bone marrow concentrate, in particular, offers added benefits due to its growth factors. However, clinical trials show mixed results, suggesting a gap between laboratory and clinical outcomes. (Nicolas Morton-Gonzaba, Daniel Carlisle, Chimobi Emukah, et Al. 2020).

Timing and Standardization

Early mesenchymal stem cell treatment, ideally within three days post-injury, may yield the best results, though this is often unfeasible due to surgery delays. Standardizing stem cell origin, timing, and delivery methods will be essential to enhance consistency in future research.

Arthroscopic Surgery Versus Mesenchymal Stem Cell Therapy

Arthroscopic surgery is commonly used for chronic shoulder pain, but it poses risks, including stiffness, nerve injuries, and implant complications. Mesenchymal stem cell therapy is emerging as an alternative for treating rotator cuff injuries.

Clinical Trials on Mesenchymal Stem Cells

As of late 2019, several trials (three ongoing and six completed) investigated mesenchymal stem cell therapy for rotator cuff injuries. These trials used stem cells from bone marrow or fat tissue, with some studies combining mesenchymal stem cells with surgery, while others used ultrasound-guided injections.

Promising Results from Completed Trials

1. Fewer re-tears even after 10 years

2. Enhanced shoulder function and tendon health based on MRI scans

3. Reduced tissue damage on joint and bursa (shoulder structures) according to arthroscopic evaluations

4. Minimal adverse effects related to stem cell treatment

Conclusion

Rotator cuff injuries present complex challenges due to their tendency for re-tearing and potential for long-term functional limitations. While arthroscopic surgery is a common treatment, it carries risks like stiffness, nerve damage, and implant complications. Mesenchymal stem cell therapies have shown potential to improve healing and reduce re-tear rates. Clinical trials indicate that mesenchymal stem cells, whether combined with surgery or administered through ultrasound-guided injections, can enhance recovery and reduce complications. Continued advancements in regenerative medicine hold promise for transforming rotator cuff injury management, leading to improved, lasting patient outcomes.

References

1.     Hao-Nan Wang, Xiao Rong, Lu-Ming Yang et Al. 2022. Advances in Stem Cell Therapies for Rotator Cuff Injuries. Frontiers in Bioengineering and Biotechnology May 2022 | Volume 10 | Article 866195    

2.     Ranjan Gupta, MDa, Rohan Rao, BSa, Tyler R. Johnston, MD et Al. 2021 Muscle stem cells and rotator cuff injury. JSES Reviews, Reports, and Techniques 1 (2021) 186e193

3.     Zetao Wanga, Youguo Liao, Canlong Wang et. Al 2023. Stem cell-based therapeutic strategies for rotator cuff tendinopathy. Journal of Orthopaedic Translation 42 (2023) 73–81

4.     Seyed Peyman Mirghaderi, Zahra Valizadeh, Kimia Shadman et Al. 2022. Cell therapy efficacy and safety in treating tendon disorders: a systemic review of clinical studies Journal of Experimental Orthopaedics (2022) 9:85

5.     Nicolas Morton-Gonzaba, Daniel Carlisle, Chimobi Emukah, et Al. 2020. Mesenchymal stem cells and their application to rotator cuff pathology: A meta-analysis of pre-clinical studies. Osteoarthritis and Cartilage Open 2 (2020) 100047