Stem Cell Research: Tendonitis

Follow-up Duration: Patients were followed for up to 2 years.

Primary Outcome: To determine if there was greater improvement in pain during activity at 3 months in the stem cell group.

Key Findings:

• No Difference in Pain or Function: The study’s primary goal was not met. There were no statistically significant differences in pain or shoulder function between the groups at any point during the 2-year follow-up.
• All Groups Improved: All patients, including those who received placebo injections, improved over time — suggesting recovery may have been due to time or the injection procedure itself.
• No Structural Healing on MRI: MRI scans at 12 weeks and 12 months showed no significant difference in tendon healing between groups.
• Safety: MSC injection was safe. The only side effect was temporary pain at the injection site, with similar severity and duration across all groups. No serious adverse events occurred.

Limitations Identified by the Researchers:

• The study had a small sample size (24 patients).
• Control groups didn’t receive a pure sham intervention — the needle and fibrin glue themselves may have had therapeutic effects.

Researchers’ Conclusion:

• A single injection of MSCs with fibrin glue was not superior to fibrin glue with saline or saline alone for treating partial supraspinatus tendon tears.
• The treatment was safe, but this study did not support its effectiveness for this condition.

Delivery Method:

• Each patient received a single injection of stem cells directly into the damaged part of their Achilles tendon.
• The injection was guided by ultrasound to ensure precise placement.

Cell Type & Source:

• Autologous mesenchymal stem cells, from the patient’s own body.
• Source: Bone marrow, taken from the iliac crest (hip bone).
• Cells were cultured and expanded in a lab.

Dosage:

• Each patient received a single dose.
• Median dose: 12.2 million cells (range: 5–19 million cells).

Safety:

• No serious adverse reactions or medical events were reported during the 24-week study.
• The procedure was well-tolerated, with no complications from either bone marrow collection or injection.

Clinical Improvements:

• MOXFQ score: Dropped from 52 to 24 at 24 weeks (lower = better foot/ankle pain and function).
• VISA-A score: Increased by 22 points at 24 weeks (higher = less Achilles pain/severity).
• 8 out of 10 patients had a “successful outcome” (clinically meaningful improvement in pain/function).

Physical Tendon Changes (from Ultrasound):

• Tendon thickness decreased by an average of 0.8 mm at 24 weeks.
• Advanced ultrasound showed no significant improvement in internal tissue organization.
• No change in abnormal blood vessel presence.

How the Cells Worked:

• The exact mechanism is unclear.
• Two main theories:
  • Paracrine effect: MSCs released healing/anti-inflammatory molecules.
  • Differentiation: MSCs turned into new tendon cells.
• Because tendon structure didn’t improve, researchers believe pain relief likely came from reduced inflammation, not structural repair.

What We Don’t Know:

• No placebo group. Hard to tell how much was a placebo effect.
• Very small sample size (10 patients).
• Ideal dosage is still unknown.
• Unclear how much post-injection physiotherapy contributed to the improvements.

Conclusion:

• This study showed that injecting a patient’s own cultured bone marrow MSCs is safe for treating chronic Achilles tendinopathy.
• Patients improved in pain and function, with no serious side effects reported.
• The results support moving forward with a larger, randomized controlled trial.

Delivery Method:

• Each patient received a single injection of their own stem cells.
• Injection was guided by ultrasound and targeted the damaged area of the common extensor tendon in the elbow.

Cell Type & Source:

• Autologous adipose-derived mesenchymal stromal cells (from the patient’s own fat tissue).
• Fat collected from around the belly button using a minimally invasive method.
• Cells were isolated and cultured in a lab for about a month.

Dosage:

• A single dose per patient, averaging 7.9 million cells.

Safety:

• No serious side effects reported.
• 2 patients developed a temporary hematoma at the fat harvest site (resolved without intervention).
• 6 patients reported mild discomfort at the elbow injection site.

Clinical Improvements:

• Pain (VAS score): Dropped from 6.28 → 0.74 at 12 months (lower is better).
• Disability (QuickDASH score): Improved from 51.38 → 5.56 at 12 months (lower is better).
• All 18 players returned to tennis within an average of 3.3 months.
• 17 of 18 players reported being “very satisfied” at the 12-month mark.

Physical Tendon Changes (from MRI):

• MRI scans at 6 months showed significant structural repair of the tendon.
• MRI severity score: Improved from 4.22 → 2.22 (lower is better).

How the Cells Worked:

• Researchers believe the stem cells helped by:
  • Releasing healing molecules (paracrine effect)
  • Calming the immune system (anti-inflammatory action)
• Improvement in symptoms occurred quickly, even before tendon healing was visible on MRI, supporting the anti-inflammatory theory.

What We Don’t Know:

• No placebo group, so a placebo effect cannot be ruled out.
• Small sample size (18 patients).
• Outcome assessors were not blinded leaving a potential for bias.
• Follow-up limited to 12 months. Long-term effects are still unknown.

Conclusion:

• This pilot study shows that autologous, cultured fat-derived stem cell injection is a safe and promising therapy for chronic tennis elbow.
• Patients experienced lasting pain relief, regained function & returned to sport quickly.
• Authors recommend larger, more rigorous studies to confirm effectiveness.

• Is stem cell therapy effective in reducing pain and improving function in patients with tendon disorders?
• Is the treatment safe and well-tolerated?
• How do the results differ depending on the location of the injured tendon?
• What is the current state of the evidence for using cell therapy as a treatment for tendinopathy?

The Treatment is Consistently Safe.

• Across all 22 studies, the cell therapy injections were found to be safe, with no serious side effects or immune reactions reported.
• The few adverse events that did occur were minor and temporary, like pain or bruising at the injection or harvest site.

Effectiveness Depends on the Tendon

Rotator Cuff (Shoulder): This area showed the strongest and most positive results. Multiple controlled studies found that cell therapy was more effective than control treatments, leading to a lower re-tear rate after surgery and greater improvements in pain and function.

Elbow Tendinopathy: All studies reported that the treatment was effective, but none of them included a placebo or control group for a direct comparison.

Achilles & Patellar Tendinopathies: The results here were mixed and inconsistent. Some studies showed that cell therapy was superior to the control treatment, while others found no significant difference in the long-term outcomes.

Mechanism of Action is Unclear.

The review states that the exact way the cells work is not yet fully understood.

Researchers propose it could be a combination of the cells turning into new tendon cells (differentiation), releasing healing signals (paracrine effect), and calming inflammation (immunomodulation).

• The researchers strongly emphasize that the clinical evidence is still in its early stages.
• Many of the reviewed studies were poorly designed, often lacking a proper control group.
• The studies were also limited by small patient numbers and short follow-up periods.
• Finally, there was a complete lack of standardization in the types of cells used, the doses & the delivery methods, which makes it very difficult to compare results or establish a single best protocol.

This review was an update to a similar one the team did in 2017, which found no evidence to support stem cell therapy for tendons. The researchers wanted to know if new studies had changed the verdict. Their main questions were:

• Is stem cell therapy effective in helping patients with tendon disorders feel better and function better?
• Does the treatment lead to actual, measurable healing in the tendon tissue?
• Based on the current quality of evidence, can we make a clear recommendation for or against using stem cell therapy in clinics today?

The Overall Evidence is Weak.

• Every study they reviewed had a moderate to high risk of bias — meaning the positive results may not be reliable.
• The best evidence only reached “Level 3”, which is not strong enough to change clinical practice.

Effectiveness Depends on the Tendon:

• Rotator Cuff (Shoulder): Most promising results. Controlled studies showed better tendon healing and improved patient outcomes with stem cells.
• Achilles Tendon: Mixed results. One study showed faster initial recovery with stem cells vs. PRP, but no long-term difference.
• Patellar Tendon (Knee) & Elbow Tendinopathy: Small, lower-quality studies showed some benefits, but results were inconsistent.

• High Risk of Bias: The findings come from studies with significant design flaws.
• Not Ready for Clinical Use: Evidence-based recommendations “cannot be made at this time.”
• Major Safety Concerns: The review warned that stem cell injections should not be used in clinical practice due to unknown risks.
• Better Research is Needed: The authors call for large, controlled trials with 5+ years of follow-up to determine if stem cell therapy is truly safe and effective for tendons.

Previous reviews were limited and no one had ever combined statistical data from multiple studies in a meta-analysis. This review was the first attempt to do so.

Their main questions were:

• Is therapy with mesenchymal stem cells effective and safe for patients with tendon disorders?
• Does the treatment lead to actual, measurable healing in the tendon tissue, as seen on imaging and in surgery?
• Is there a relationship between the dose of stem cells given and the amount of pain relief a patient experiences?

The Overall Evidence is Promising.

• When the results of the four studies were combined, MSC therapy showed significant positive effects.
• Treatment improved all key outcomes: pain, function, imaging, and surgical findings.

Higher Doses Worked Better for Pain.

• The analysis showed a clear dose-dependent response — higher doses led to better pain relief.

There is Evidence of Tissue Regeneration.

• Imaging and arthroscopic (surgical) findings showed that the injected MSCs helped regenerate damaged tendon tissue.
• One study reported that follow-up surgery revealed regenerated tendon tissue in all MSC-treated patients.

• Limited Number of Studies: Only four studies were included, and only one was a randomized controlled trial.
• Differences Between Studies: The included studies varied in:
  • Stem cell type (bone marrow vs. fat tissue)
  • Treated tendon (rotator cuff vs. tennis elbow)
  • Use of surgery in combination with injection
  These differences made direct comparisons difficult.
• Better Research is Needed: The authors call for large, high-quality randomized trials with long-term follow-up to confirm both benefits and safety.