Are mesenchymal stem cell (MSC) injections into the shoulder joint effective in treating shoulder pain and osteoarthritis (OA) in patients who have not responded to conservative treatments such as physical therapy, nonsteroidal anti-inflammatory drugs (NSAIDs), or corticosteroid injections?

MSC Stem Cell Injections for Shoulder Osteoarthritis: Not Recommended

MSC (mesenchymal stem cell) injections are not recommended for treating shoulder pain and osteoarthritis, as they are not mentioned in any major shoulder osteoarthritis treatment guidelines and lack evidence for efficacy or safety in this specific joint. 1, 2

Why MSC Injections Are Not Guideline-Supported for Shoulder OA

The American Academy of Orthopaedic Surgeons (AAOS) 2010 clinical practice guideline on glenohumeral osteoarthritis systematically reviewed all available treatments and made 16 recommendations—MSC therapy was not among them. 1 The guideline explicitly states that "barely any data exist to guide nonsurgical treatment of GH OA," yet MSC injections were not even considered as an investigational option. 1

The absence of MSC therapy from shoulder OA guidelines is particularly notable because the AAOS guideline included even treatments with insufficient evidence (Grade I recommendations for corticosteroid injections and arthroscopy) and weak evidence (Grade C for viscosupplementation). 1, 2 If MSC injections had any meaningful evidence base for shoulder OA, they would have been evaluated.

Evidence Extrapolation from Knee OA Does Not Apply

While MSC injections have been studied for knee osteoarthritis, a 2025 Cochrane systematic review found only low-certainty evidence that stem cell injections may slightly improve knee pain and function compared to placebo, with very low certainty regarding quality of life and treatment success. 3 Importantly:

• The review downgraded evidence due to indirectness, as "the source, method of preparation and dose of stem cells varied across studies." 3
• Radiographic progression (structural joint changes) was not assessed in any included studies, meaning there is no evidence that stem cells actually modify disease progression. 3
• Serious adverse events were infrequently reported, but the certainty of safety evidence was very low. 3
• Up to three larger RCTs have been withdrawn prior to reporting results, raising concerns about publication bias. 3

The shoulder joint has fundamentally different biomechanics, loading patterns, and disease characteristics compared to the knee, making extrapolation of knee OA data inappropriate. 4

What Actually Works for Shoulder OA

For Conservative Management (First-Line):

• Exercise-based physical therapy is the foundation of treatment, focusing on decreasing pain, increasing range of motion, and rotator cuff strengthening. 2, 4
• Viscosupplementation (hyaluronic acid) is an option (Grade C recommendation), typically given as three weekly injections, with improvements lasting 1-6 months. 1, 2, 5
• Corticosteroid injections have insufficient evidence (Grade I) but are widely used in clinical practice for symptomatic flares. 1, 2

For Surgical Candidates (When Conservative Treatment Fails):

• Total shoulder arthroplasty (TSA) is preferred over hemiarthroplasty (Grade B recommendation, Level II evidence), providing superior pain relief and functional outcomes. 1, 2
• TSA should NOT be performed in patients with irreparable rotator cuff tears—reverse total shoulder arthroplasty should be considered instead. 2

Critical Pitfalls to Avoid

Do not offer MSC injections as a "bridge therapy" before arthroplasty. There is no evidence that MSC injections delay disease progression or improve surgical outcomes in shoulder OA. 1, 2 The AAOS guideline emphasizes that "considerable controversy remains regarding various surgical techniques," yet MSC therapy is not even part of this controversy because it lacks any shoulder-specific evidence. 1

Do not extrapolate biologics evidence from other joints to the shoulder. While platelet-rich plasma and bone marrow aspirate concentrate have been studied in shoulder conditions, a 2023 review concluded that "biologics are helpful in decreasing shoulder pain but neither stopping the progression nor improving OA" and that "further evidence needs to be obtained to determine their effectiveness." 4

Recognize that MSC therapy remains investigational even in knee OA, where it has been most extensively studied. 6, 3 The theoretical mechanisms by which stem cells might slow disease progression remain unclear, and structural joint changes have not been demonstrated. 6, 3

The Bottom Line

For patients with shoulder OA who have failed conservative treatments (physical therapy, NSAIDs, corticosteroid injections), the evidence-based pathway is total shoulder arthroplasty, not experimental biologics. 1, 2 MSC injections lack guideline support, shoulder-specific evidence, and proof of disease modification. Patients seeking MSC therapy should be counseled that this represents an unproven, costly intervention with unknown long-term safety and no demonstrated superiority to established treatments. 1, 2, 3