Are stem cell therapy knee injections effective for treating knee conditions like osteoarthritis?

Stem Cell Therapy for Knee Osteoarthritis

Stem cell injections are strongly recommended against for knee osteoarthritis based on major clinical practice guidelines, primarily due to lack of standardization in preparations and techniques, making it impossible to determine what is actually being injected. 1

Guideline-Based Recommendations

Strong Recommendation Against Use

• The 2019 American College of Rheumatology/Arthritis Foundation guidelines provide a strong recommendation against stem cell injections for knee and hip osteoarthritis 1

• The primary concerns driving this recommendation include:

  • Heterogeneity and lack of standardization in available stem cell preparations 1
  • Variable techniques used across different providers, making it difficult to identify exactly what is being injected 1
  • Absence of FDA approval or regulatory oversight for these preparations 1

• The 2020 VA/DoD Clinical Practice Guidelines similarly suggest against the use of stem cell injections for hip and knee osteoarthritis, acknowledging insufficient evidence to support their use 1

Research Evidence Context

Recent Cochrane Review Findings

• A 2025 Cochrane systematic review (25 trials, 1,341 participants) found that stem cell injections may slightly improve pain and function compared to placebo at 3-6 months, but this evidence is low certainty 2

• Pain improvement: 1.2 points better on 0-10 scale (low certainty evidence with high heterogeneity, I² = 80%) 2

• Function improvement: 14.2 points better on 0-100 scale (low certainty evidence with high heterogeneity, I² = 82%) 2

• Critical limitation: The evidence was downgraded due to indirectness (source, preparation method, and dose varied substantially across studies) and suspected publication bias (up to 3 larger trials were withdrawn before reporting results) 2

Safety Concerns

• Serious adverse events are uncertain due to very low event rates and very low certainty evidence 2

• Mesenchymal stem cell intravenous infusion carries thrombosis risk, particularly at high doses, with significant increases in coagulation parameters 3

• Adipose-derived mesenchymal stem cells show high procoagulant activity in preclinical models 3

• All invasive joint procedures carry a small risk of septic arthritis 2

• Unknown long-term risks related to therapies with theoretical capacity to promote cell growth or use of allogeneic cells 2

Critical Pitfalls to Avoid

The Standardization Problem

• There is no standardized stem cell product for knee osteoarthritis—different clinics use different cell sources (bone marrow, adipose tissue, peripheral blood), different preparation methods, and different doses 1, 2

• This heterogeneity means that even if some preparations show benefit, you cannot extrapolate results from one study to what is being offered at a specific clinic 2

The Evidence Quality Gap

• Most trials are small and at high risk of bias 4

• The 2017 systematic review concluded all trials had high risk of bias, resulting in only level-3 evidence, insufficient to recommend use 4

• No trials have assessed radiographic progression, leaving the purported regenerative effects on cartilage unproven 2

Commercial vs. Clinical Reality

• Stem cell therapy is increasingly marketed directly to consumers despite lack of high-quality evidence 2, 5

• The absence of FDA approval means no quality control or standardization of what patients receive 1

Recommended Treatment Algorithm for Knee Osteoarthritis

Instead of stem cell therapy, follow evidence-based treatments:

1. First-line interventions (all have strong evidence):

   • Self-management programs and patient education 1
   • Physical therapy 1
   • Topical NSAIDs and capsaicin for knee pain 1

2. Second-line pharmacotherapy:

   • Oral NSAIDs for knee pain 1
   • Acetaminophen for knee pain 1
   • Duloxetine for knee pain 1

3. Injection therapy when other treatments fail:

   • Intra-articular corticosteroids (evidence-supported) 1
   • Hyaluronic acid may be considered in shared decision-making when other alternatives are exhausted (conditional recommendation against, but allows for use in specific contexts) 1

4. Avoid:

   • Stem cell injections (strong recommendation against) 1
   • Platelet-rich plasma (strong recommendation against) 1
   • Opioids or tramadol 1

Important Exception: Avascular Necrosis

Note that stem cell therapy has a completely different evidence base for avascular necrosis of the hip (not osteoarthritis), where bone marrow-derived stem cells combined with core decompression show benefit in early-stage, pre-collapse disease 6

• This is not applicable to knee osteoarthritis, which is a different pathophysiological process 6