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 (23 patients).
• The treatments used for comparison may have contributed to healing on their own, as the injection itself and fibrin glue may have also aided in healing.
• Patients had shoulder pain for different lengths of time, which can affect natural recovery.
• Some participants had only mild pain at the start of the study, leaving little room for noticeable improvement.
• A few patients had calcium deposits in the tendon, which may interfere with healing.
• In some cases, the injected stem cells may not have stayed fully at the injury site.

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.

Procedure

Patients were randomly split into:

• Bone marrow/stem-cell augmentation + surgery group
• Surgery-only control group

Both groups had arthroscopic rotator cuff repair.

Meaning:

• The surgeons used keyhole shoulder surgery
• They repaired the torn tendon using anchors and stitches

Cells Used

Autologous bone marrow aspirate concentrate / BMAC.

Meaning:

• The bone marrow came from the patient’s own body
• It was used during the same surgical procedure
• This was not cultured or lab-expanded stem cells

Dosage

Patients in the bone marrow/stem-cell group received a total of:

• 6 mL injection

This was split into:

• 3 mL injected into the tendon-bone junction
• 3 mL injected into the bone at the surgical repair site.

Follow-up Duration

Primary result:

• 1 year

Safety reporting:

• 2 years

Patients also completed shoulder exams and questionnaires up to 24 months after surgery.

Primary Outcome: ASES Shoulder Score

ASES = American Shoulder and Elbow Surgeons score.

This is a shoulder questionnaire that measures:

• Pain
• Activity level
• Shoulder function
• Stability

The score goes from:

• 0 to 100

Meaning:

• Higher score = better shoulder function
• 90-100 = excellent
• 70-89 = good
• 40-49 = fair
• Below 39 = poor.

Main Result

Bone Marrow / Stem Cell Group:

• ASES score: 87

Surgery-Only Group:

• ASES score: 89

• ➡ Both groups had good shoulder function after surgery.
• ➡ BUT the bone marrow/stem-cell group was not better than the surgery-only group.
• ➡ The surgery-only group actually had a slightly higher average score.

Did the BMAC / Stem Cell Treatment Work?

Based on the main result:

• No clear added benefit was shown.

The important point:

• Both groups had rotator cuff repair surgery
• Both groups did well
• But adding BMAC/stem-cell augmentation did not improve the main 1-year shoulder score compared with surgery alone

So the plain-English conclusion is:

• The surgery helped patients recover well
• The added BMAC/stem-cell treatment did not appear to add extra benefit

Safety

The treatment appeared safe in this trial.

During the 2-year adverse-event reporting period, the study reported:

• No deaths
• No serious adverse events
• No other adverse events

This was true in both groups:

• 0/28 in the bone marrow/stem-cell group
• 0/34 in the surgery-only group.

Based on the posted results:

• Adding autologous bone marrow concentrate during rotator cuff repair appeared safe in this study
• No adverse events were reported during the 2-year safety reporting period
• Patients in both groups had good shoulder function after surgery
• HOWEVER, the bone marrow/stem-cell group was not better than the surgery-only group on the main 1-year ASES score
• Therefore, this trial does not show that BMAC/stem-cell augmentation provides extra clinical benefit over standard rotator cuff repair surgery alone.

Procedure

Patients had bone marrow taken from the back of the pelvis/hip bone.

The researchers then isolated and expanded the patient’s own bone marrow-derived mesenchymal stem cells in a lab.

Several weeks later, those cells were injected into the damaged area of the Achilles tendon.

Delivery Method

The cells were injected directly into the Achilles tendon using ultrasound guidance (intratendinous injection).

Cells Used

Autologous cultured bone marrow-derived mesenchymal stem cells

Dosage

The median dose was:

• 12.2 million BMMSCs

Range:

• 5 million to 19 million cells

The researchers aimed for:

• Minimum target: 4 million cells
• Ideal target: 20 million cells

But the actual dose varied because each patient’s cells grew differently in culture.

Culture Method

The bone marrow sample was processed in a GMP facility licensed by the UK MHRA.

GMP means Good Manufacturing Practice, which is the controlled manufacturing standard used for medical products.

The cells were:

• Isolated from bone marrow mononuclear cells
• Expanded over 28–43 days
• Expanded through up to three passages

Cell Testing

Before injection, the final cell product had to show:

• More than 90% MSC identity
• More than 95% cell viability
• MSC markers:
• CD73
• CD90
• CD105
• Sterility / aseptic preparation

Physiotherapy

After the injection, patients completed a standard 12-week eccentric loading physiotherapy programme for Achilles tendinopathy.

This is important because physiotherapy itself can improve Achilles tendinopathy.

Follow-up Duration

Patients were followed for 24 weeks after the stem-cell injection.

Primary Outcome: Safety

The main goal was to check safety.

Results:

• No serious adverse reactions
• No important medical events
• No complications from bone marrow harvest
• No complications from the injection procedure

So the treatment appeared safe in this small group over 24 weeks.

Pain: VAS Pain Score

VAS pain was measured on a 0–100 scale, where lower numbers mean less pain.

Pain improved from:

• 43 → 22

That means patients reported less pain by 24 weeks.

Achilles Function: VISA-A Score

VISA-A is a score used for Achilles tendon problems.

Higher scores mean better Achilles function.

VISA-A improved from:

• 41 → 61

That means Achilles-specific function improved by 24 weeks.

Foot and Ankle Function: MOXFQ

MOXFQ is a foot and ankle questionnaire.

Lower scores mean fewer problems.

MOXFQ pain improved from:

• 52 → 25

MOXFQ walking improved from:

• 53 → 25

MOXFQ social interaction improved from:

• 43 → 24

So patients reported better walking, less pain, and better daily/social function.

Overall Success

At 24 weeks:

• 8 out of 10 patients met the study’s definition of a successful outcome.

The researchers defined success using meaningful improvements in outcome scores, including pain and Achilles function.

Ultrasound / Tendon Structure

The ultrasound results were more limited.

The maximum tendon thickness decreased by about:

• 0.8 mm at 24 weeks

But other ultrasound measures did not clearly improve, including:

• Lesion size
• Percentage of disorganized tendon tissue
• Neovascularization
• Ultrasound tissue characterization fibre type

Plain English:

• Patients felt and functioned better, but the imaging did not strongly prove that the tendon structure had regenerated.

Safety

The treatment appeared safe in this small group.

Reported safety findings:

• No serious adverse reactions
• No important medical events
• No complications from the bone marrow harvest
• No complications from the injection procedure

How the Cells May Have Worked

The researchers said the exact mechanism is not fully understood.

They suggested possible explanations including:

• MSCs releasing paracrine factors
• MSCs helping coordinate the body’s repair response
• MSCs having an immunomodulatory effect, meaning they may help regulate inflammation
• Possible direct action of stem cells becoming tendon-like cells

However, the study did not prove exactly how the cells worked.

The researchers also said the clinical improvements could be due to:

• The MSCs
• The needling/injection effect
• Physiotherapy
• Placebo effect
• Changes in inflammation and pain rather than true tendon regeneration

The researchers concluded that injecting a patient’s own expanded bone marrow MSCs into the Achilles tendon appeared safe in this small study.

Patients had encouraging improvements in pain and function.

But the researchers said a larger randomized controlled trial is needed to prove whether the treatment is truly effective.

• 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. but results were not uniform across all studies.

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.The review also included one study where stem cells were used as an add-on during Achilles tendon rupture surgery, and no re-ruptures were reported.
• 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.

• The review highlights that the improvements weren’t just in how patients felt. Imaging and arthroscopic findings suggested that the injected cells may have contributed to the healing of the 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.