Stem Cell Therapy Research: Knee Treatments

Procedure

Delivery Method:

• Three ultrasound-guided intra-articular injections directly into the knee joint

Injection Timing:

• Dose 1: Baseline
• Dose 2: Week 3
• Dose 3: Week 52 (12-month mark)

Cell Dosage:

• 2.5 × 10⁷ MSCs (25 million cells) per injection

Administered by a radiologist under blinded conditions

Cell Type Used

Allogenic Mesenchymal Stem Cells (MSCs)

Specifically: Mesenchymoangioblast-derived MSCs (lab-grown stem cells made by turning early adult cells like a skin cell into mesenchymal stem cells in a controlled, high-purity process.)

How Cells Were Prepared

Source: The cells came from a healthy adult and were grown in the lab to create a master cell bank

Manufacturing: The cells are grown using a carefully controlled process, tested for safety and quality, to make sure every batch is consistent and meets medical standards.

Next Steps

• Follow-up ongoing for all participants through 24 months after their final injection (i.e., into late 2025)
• Primary outcomes (pain reduction and cartilage thickness changes) to be assessed at 24 months
• Secondary outcomes include quality of life, MRI-based structural changes, economic analysis (QALYs), and participant-reported outcomes
• Results are not yet published; final analysis expected after study wraps up in 2025

Procedure

Delivery Method:

• Single intra-articular injection into the knee joint following lipoaspiration (fat tissue collection).

Treatment Groups

• JointStem Group: Autologous adipose-derived mesenchymal stem cells (AdMSC) injection.
• Placebo Group: Normal saline with autologous serum.

Blinding:

• Triple-blind design (participants, investigators and outcome assessors are blinded).

Duration:

• 48-week follow-up with visits at weeks 4, 12, 24, 36 and 48.

What They’re Looking For

Primary Outcomes (Efficacy):

• Pain reduction: Change in Visual Analogue Scale (VAS) pain score from baseline to 48 weeks.
• VAS is a simple pain scale where patients rate their pain from 0 (no pain) to 10 (worst pain imaginable).
• Function improvement: Change in WOMAC (Western Ontario and McMaster Universities Arthritis Index) function score from baseline to 48 weeks.
• WOMAC is a questionnaire that measures knee osteoarthritis symptoms, including pain, stiffness, and ability to perform daily activities.

Secondary Outcomes (Function, Structure & Quality of Life):

• WOMAC subscales (Pain & Function): Measured at weeks 12, 24, 36, and 48.
• Total WOMAC score: Combined pain, stiffness, and function scores.
• IKDC (International Knee Documentation Committee) score: Knee-specific function and symptoms.
• SF-36 (Short Form-36): General health and quality of life assessment.
• Joint structure changes: Kellgren-Lawrence (X-ray) grade at week 48
• Rescue medication use: Amount and frequency of paracetamol use during the trial

Next Steps

• Recruitment: The trial is still recruiting across multiple sites in the US (California) and Korea (Seoul and Daegu).
• Follow-up: Each participant will be followed for 48 weeks to monitor pain relief, knee function, and joint health.
• Analysis: After all participants complete their 48-week visit, data will be analyzed for efficacy and safety.
• Completion: Final results are expected after full follow-up in December 2026.

Procedure

Delivery Method:

• Single intra-articular injection directly into the knee joint.

Dosage:

• Participants are divided into 3 sequential groups using a “3+3” safety model:
• – Low Dose: 5 × 10⁶ cells (5 million) / 2.5 mL
• – Medium Dose: 1 × 10⁷ cells (10 million) / 2.5 mL
• – High Dose: 2 × 10⁷ cells (20 million) / 2.5 mL

Each dose level is tested in 3–6 participants before escalating to the next.

Cell Type Used: Umbilical Cord-Derived Mesenchymal Stem Cells

What They’re Looking For

Primary Outcome (Safety):

• Monitor how many patients experience side effects and how serious they are in the first 4 weeks after the injection.

Secondary Outcomes (Early Efficacy Signals):

• Pain reduction: Visual Analogue Scale (VAS) scores at 24 hours, 4, 12, 24, and 48 weeks.
• VAS is a simple pain scale where patients rate their pain from 0 (no pain) to 10 (worst pain imaginable).
• Function improvement: WOMAC Index scores (pain, stiffness, mobility).
• WOMAC is a questionnaire that measures knee osteoarthritis symptoms, including pain, stiffness, and ability to perform daily activities.
• Joint structure changes:
• MRI cartilage repair scores (Roberts Score).
• X-ray Kellgren-Lawrence grade and joint space width.
• Mobility gains: Knee range of motion (ROM) changes over 48 weeks.

Next Steps

• Recruitment: The trial is still recruiting and needs to enroll up to 18 participants (currently in progress).
• Dose Escalation: Participants will be treated in small groups (3–6 people per dose level). After each group completes the 4-week safety check, the next higher dose group will begin.
• Follow-up: All participants will be followed for up to 48 weeks after their injection to assess pain relief, knee function, and cartilage repair.
• Completion: The trial is expected to have a full follow-up by October 2026.

Study Details

How Cells Were Prepared

• The stem cells were taken from donated fat using liposuction, then treated with enzymes to separate the stem cells from the rest of the fat tissue. They were then cultured to passage 4
• After culturing, they were tested using ISCT criteria:
• – Positive: CD105, CD90, CD73. These markers confirm the cells are true mesenchymal stem cells, with over 95% showing the expected regenerative identity.
• – Negative: CD45, CD14, CD34, CD19. These markers are found on blood and immune cells, so having less than 2% means the stem cell sample was very pure and not contaminated with unwanted cell types.
• The cells were checked to make sure they were free from contamination (bacteria, hidden infections, toxins), and that their DNA was stable and hadn’t mutated during lab growth aka: Sterility, MycoPlasma, Endotoxins, Karyotype stability
• The stem cells were then frozen and stored in 1 mL vials, each containing 10 million cells, using a special solution (CryoStor® CS10) that protects them during freezing.
• Delivered in blinded syringes to prevent trial bias

Results

No serious adverse events across any dose group

Overall, 75% of the people who received the stem cell treatment saw meaningful improvement in pain or function.

Magellan Also tracked results from MRI’s too:

• MRI scans taken 12 months later showed that people in the placebo group had lost cartilage in their knees, meaning their osteoarthritis got worse over time.
• People who received the stem cell treatment generally kept more of their knee cartilage, especially in one key area of the joint (the lateral femoral condyle). The 20 million cell group showed a clear, statistically significant benefit in that spot.
• The MRI didn’t show clear, measurable regrowth of cartilage across the whole knee that was strong enough to rule out chance. So while some areas improved, the overall joint didn’t show proven cartilage regrowth.

How Cells Worked

The stem cells likely worked by sending healing signals, not by turning into new tissue themselves. These signals helped reduce inflammation, calm the immune system, and support the body’s natural repair process. There’s no evidence in this trial that they worked by becoming cartilage-producing cells (differentiation).

What we Don’t Know

The study didn’t include any tests to track what happened to the stem cells in the body . So we don’t know if they stayed in the joint, survived long-term, or turned into cartilage We don’t know what happens after 12 months

Next Steps

This was a solid, thoughtfully run study with some genuinely interesting results. Magellan Stem Cells is now gearing up for phase three clinical trials this year (2025) with the support of a $7 million research grant from the Australian Government.

Study Details

Procedure: Split into 2 Groups:

• 12 knees treated with AD-MSCs, 12 knees treated with saline

Delivery method: Single intra-articular injection into the knee joint

Cell used: Autologous adipose-derived mesenchymal stem cells (AD-MSCs)

Dosage:

• Each patient received 100 million stem cells, mixed into 3 milliliters of saline, which was then injected into their knee. (saline ensures the stem cells stay alive, stable, and safe during injection)

Control group: This group received 3 mL saline only

Blinding: Neither the patients nor the doctors knew who received the real stem cell treatment and who got the placebo.

Follow-up: 1, 3, and 6 months

How Cells were prepared:

Source:

• Fat was taken from under the skin of the belly using a gentle liposuction procedure.

Culture method:

• The fat tissue was broken down using an enzyme called collagenase so that the stem cells could be separated from the rest of the material.
• The stem cells were grown in a nutrient-rich liquid (Keratinocyte-SFM media with rEGF, FBS) that helped them multiply, containing ingredients like growth factors, proteins, and vitamins to keep them healthy and active.

Passage: Cells used at Passage 3

Purity testing:

Positive markers:

• CD73, CD90. These markers confirm the cells are true mesenchymal stem cells (One thing to note is strictly, the ISCT says that true mesenchymal stem cells must have all three markers: CD73, CD90, and CD105.)

Negative markers:

• CD31, CD34, CD45.
• CD31, CD34, and CD45 are proteins found on blood or immune cells, so if stem cells don’t have them, it shows the sample is clean and not mixed with the wrong types of cells. (The ISCT says other markers like CD14, CD19, and HLA-DR should also be checked to make sure the stem cells aren’t mixed with immune cells, which could cause unwanted reactions or reduce the treatment’s effectiveness.

Viability:

• On the day of injection, nearly all the stem cells were alive and healthy. With about 93% survival on average, which means they were in good condition to work effectively.

Sterility tests:

• The cells were tested to make sure they were clean and free from bacteria, fungi, and other harmful contaminants before injection.

Storage: Frozen at −196°C and thawed on day of use

Results

Primary outcome (WOMAC score):

• The group that received stem cells had a 55% improvement in symptoms. Their average score dropped from 60 to 26.7 and the result was statistically very strong (p < .001), meaning it’s very unlikely to be due to chance.
• Control group: No significant change

VAS pain score:

• MSC group dropped from 6.8 → 3.4 (p < .001). (The VAS pain score is a simple 0 to 10 scale where patients rate their pain)

KOOS scores:

• All subscales improved significantly in MSC group only. (a questionnaire that measures how knee problems affect someone’s pain, daily activities, sports ability, and quality of life.)

MRI cartilage defect:

• MRI scans showed that the stem cell group’s cartilage damage stayed the same, while the placebo group’s cartilage damage got noticeably worse
• Meaning the Stem Cells helped stop further cartilage loss.

People who received stem cells were able to move their knee more easily after treatment, their range of motion improved

Adverse events:

• No Serious events were reported!

How Cells Worked

The stem cells helped by sending out healing signals that reduced inflammation and supported tissue repair.

They did not turn into new cartilage cells themselves.

MRI scans showed that the damaged cartilage didn’t get worse, but it also didn’t grow back within 6 months.

Conclusion

Long-term effects beyond 6 months are unknown.

This study shows that a single stem cell injection can safely reduce pain, improve movement, and help stop further knee damage in people with osteoarthritis. BUT it doesn’t regrow cartilage, at least not within 6 months.

Procedure

Split into 2 groups:

• 13 Received Stem Cells & 13 didn’t

Local Stem Cell injection into the joint (intra-articular), guided by ultrasound

Timing:

• Injected 1 week after surgery

Cells Used:

• Adipose-Derived Mesenchymal Stem Cells (ADMSCs derived from Fat)

Dose:

• Each patient received 100 million stem cells, mixed into 3 milliliters of saline), which was then injected into their knee. (saline ensures the stem cells stay alive, stable, and safe during injection)

Control group:

• Received MOWHTO only (no injection)

How Cells Were Prepared:

Fat was taken from under the skin of the belly using a gentle liposuction procedure.

Culture Method:

• The fat tissue was broken down using an enzyme called collagenase so that the stem cells could be separated from the rest of the material.
• The stem cells were separated & grown in a nutrient-rich liquid (Keratinocyte-SFM media with rEGF, FBS) that helped them multiply, containing ingredients like growth factors and proteins to keep them healthy and active

Expansion:

• Cultured to passage 3

Testing before injection:

On the day of injection, more than 80% of the stem cells were alive and healthy. Meaning they were in good condition to function properly and support cartilage repair over the next several days.

• The cells were tested to make sure they were clean and free from bacteria, fungi, and other harmful contaminants before injection.
• Negative for CD31, CD34, CD45. CD31, CD34, and CD45 are proteins found on blood or immune cells, so if stem cells don’t have them, it shows the sample is clean and not mixed with the wrong types of cells. (The ISCT says other markers like CD14, CD19, and HLA-DR should also be checked to make sure the stem cells aren’t mixed with immune cells, which could cause unwanted reactions or reduce the treatment’s effectiveness.)
• Positive for CD73, CD90. These markers confirm the cells are true mesenchymal stem cells (One thing to note is strictly, the ISCT says that true mesenchymal stem cells must have all three markers: CD73, CD90, and CD105.)

Full Results

Follow-up period:

• 24 months (serial MRIs at 3, 6, 18, and 24 months)

Cartilage regeneration:

• At 24 months, the group that received stem cells showed 81% cartilage regeneration on MRI, compared to 44% in the surgery-only group. This means new cartilage grew in the damaged areas! But the doctors didn’t test the tissue directly, so they don’t know if it was the same strong cartilage you’re born with or a weaker type.
• The ADMSC group had significantly higher MOCART 2.0 scores. Meaning the new cartilage they grew looked more complete and healthier on MRI compared to the surgery-only group.
• The new cartilage looked healthier and more complete on MRI in the stem cell group, with 69.2% of patients showing total cartilage regeneration, compared to just 23.1% in the surgery-only group. While it looked closer to normal on scans, the doctors didn’t test the tissue directly, so it’s unclear whether it was the strong, original type of cartilage or a weaker version.

KOOS-ADL scores significantly improved in ADMSC group at 18 and 24 months. ((a questionnaire that measures how knee problems affect someone’s pain, daily activities, sports ability, and quality of life.)

Patients who received stem cells had better WOMAC scores, meaning they reported less pain and stiffness. But the difference wasn’t strong enough to prove it was definitely due to the stem cells.

Adverse Events:

• No Serious adverse events reported!

How Cells Worked

The researchers believe the stem cells helped by releasing healing signals, not by turning into cartilage themselves. They suggested that molecules like TSP-2, which the stem cells naturally release, likely triggered the body’s own repair process.

What We Don’t Know

• Small sample size and limited demographic diversity. Everyone was Korean.
• It’s unclear how strong or long-lasting the new cartilage is, since the type of tissue wasn’t confirmed under a microscope.

Conclusion:

Adding stem cells to knee surgery helped patients grow back more cartilage and the new tissue looked healthier on scans compared to surgery alone. While the cartilage type wasn’t confirmed under a microscope, the results suggest stem cells may support joint repair by sending healing signals, not by becoming cartilage themselves. Patients in the stem cell group also reported feeling slightly better, though this wasn’t strong enough to prove. Overall, the treatment appeared safe and showed promising signs of better recovery.

Study Details

Procedure:

• Patients were split into three groups to test different types of stem cells, and each of those groups also included a smaller set of patients who got steroid injections for comparison.

Delivery Method:

• All treatments were injected directly into the knee joint under ultrasound guidance.

Cells Used:

• BMAC: Autologous bone marrow aspirate concentrate (minimally manipulated MSC-containing mixture)
• SVF: Autologous adipose-derived stromal vascular fraction (includes MSCs and other regenerative cells)
• UCT-MSCs: Allogeneic (donor-derived) human umbilical cord tissue mesenchymal stromal cells

Dosage:

• The study didn’t report the exact number of cells used in the bone marrow or fat-derived stem cell treatments
• Patients in the umbilical cord stem cell group received a consistent dose of 20 million

Culture Method

Bone Marrow Cells:

• Harvest: Doctors collected bone marrow from the back of the patient’s hip bone using a needle to draw out stem cells for same-day injection.
• Processing: The bone marrow was spun in an FDA-approved machine to concentrate a mix of cells. Not to isolate Mesenchymal stem cells. So the final product includes a small number of MSCs along with many other cell types.
• Testing: Before the stem cell mixture was injected, it was checked to make sure it had enough total cells, that the cells were alive and healthy, and that it was free from harmful contamination like bacterial toxins.
• However, they did not test whether the cells had specific stem cell markers (like CD105, CD90, or CD73). So they didn’t confirm how many of the cells were actually MSCs.

Fat Derived Cells

• Harvest: Doctors used a gentle liposuction procedure to collect a small amount of fat from the patient to prepare the stem cell injection.
• Processing: The fat was processed to extract a mix of healing cells (called stromal vascular fraction) but it didn’t isolate just the stem cells. The final injection contained a variety of cell types, including some MSCs.
• Testing: Like BMAC, it was checked to make sure it had enough total cells, that the cells were alive and healthy, and that it was free from harmful contamination like bacterial toxins.
• However, they did not test whether the cells had specific stem cell markers (like CD105, CD90, or CD73). So they didn’t confirm how many of the cells were actually MSCs.

Umbilical Cord Derived MSC Cells

• Cultured and expanded in a GMP-certified lab
• Grown to Passage 2
• The umbilical cord stem cells were frozen and preserved in a special solution (Plasmalyte A with 5% human protein) and stored in cryobags. Small, sterile containers, at extremely low temperatures using liquid nitrogen to keep the cells alive until they were ready to use.
• Before injection, the umbilical cord stem cell batches were tested to ensure the cells were alive, safe, and free from contamination. However, the study didn’t report standard stem cell surface markers (like CD73, CD90, or CD105).
• Instead, they analyzed 8 samples using single-cell RNA sequencing, which confirmed the cells had a consistent MSC gene profile, suggesting good purity and quality.

Results

Follow-up duration:

• 12 months

Primary outcome: VAS Pain Score ( a 0–100 scale where lower numbers mean less pain)

Pain Results:

• BMAC group dropped from 58.1 → 33.8 (a –24.3 point change)
• SVF group dropped from 53.8 → 34.4 (–19.4)
• UCT group dropped from 54.3 → 34.2 (–20.1)
• Steroid group dropped from 59.9 → 39.0 (–20.9)

All groups improved, but none of the stem cell groups were statistically better than steroids (P > 0.19 in all cases)

KOOS pain score (Function & Quality of Life):

• BMAC group: Increased by +19.1 points
• SVF group: +17.2
• UCT group: +16.2
• Steroid group: +17.7

➡️ Again, no significant difference between any of the treatments (P-values all > 0.44)

MRI cartilage damage:

• MRI scans showed no structural improvement in cartilage in any group, and no major worsening either.
• No treatment prevented or reversed cartilage loss over 12 months.

Safety:

• No serious adverse events
• Minor side effects (e.g., swelling, bruising) were more common in SVF group

How Cells Worked

No direct proof of differentiation into cartilage or other knee tissues.

The stem cells appeared to work by sending signals that reduce inflammation and support the joint environment, rather than by turning into new cartilage

What We Don’t Know

• Long-term outcomes beyond 12 months the study did not assess durability or delayed benefits.
• Dose–response relationship especially for autologous groups, exact MSC counts were not standardized or disclosed.

Researchers Conclusions:

• All treatments, including stem cells and steroids, improved pain and knee function at 12 months.
• No stem cell treatment (BMAC, SVF, or UCT) was better or worse than corticosteroids (CSI) in reducing pain or improving quality of life.
• MRI scans showed no structural improvement in joint cartilage for any group.

The researchers concluded that while stem cell therapies are safe, they do not offer better or worse results than steroid injections after 1 year.

Procedure

Delivery method:

• Intra-articular injection into the knee joint

Dosage:

• 1 × 10⁸ cells (100 million cells), single injection

Control Group:

• Received saline placebo injection

Blinding:

• Double-blind (patient and investigator)

Cell Type Used

Cell type:

• Autologous adipose-derived mesenchymal stem cells (ADMSCs)

Source:

• The stem cells were collected from their own fat tissue using a small liposuction procedure.

How Cells Were Prepared

Isolation:

• The fat tissue was broken down using enzymes to separate the stem cells (MSCs) from the rest of the material, allowing them to be expanded in the lab and later injected into the knee.

Expansion:

• Cells were culture-expanded under GMP conditions to reach the target dose

Full Results and Success Rates

Primary outcomes (6-month follow-up):

VAS Pain Score Improvement (a simple 0 to 10 scale where patients rate their pain):

• Patients who received the stem cell treatment reported a 25.2 mm drop in pain on a 100 mm scale.
• Those who got the placebo still improved, but only by 15.5 mm.
• The difference was statistically significant, meaning the stem cells clearly worked better than placebo.

WOMAC Total Score Improvement (a 0–100 scale that measures how much joint pain, stiffness, and difficulty with daily activities a person has due to osteoarthritis. Higher scores mean worse symptoms):

• Patients treated with stem cells showed a 21.7-point improvement in knee function.
• The placebo group improved too, but only by 14.3 points.
• This difference was statistically significant, showing that stem cells led to better functional results.

Clinical significance:

• The stem cell group didn’t just improve more on average. More of them improved enough that it really made a difference in their daily lives.

Adverse events:

• No serious treatment-related adverse events reported

Radiologic outcomes (MRI):

• There were no clear signs that the stem cells helped regrow cartilage or improve joint structure on MRI or X-rays.

How Cells Worked

The stem cells likely helped by sending healing signals, not by rebuilding cartilage.

Even though scans didn’t show new cartilage growth, patients still felt less pain and moved better.

These improvements probably came from the stem cells reducing inflammation, supporting joint health, and calming the immune system.

What We Don’t Know

• Cartilage regeneration not proven: Despite clinical gains, no MRI evidence of tissue regrowth at 6 months
• Duration of effect unknown: Only 6-month follow-up; long-term benefits and durability are untested
• No structural outcome changes: No measurable improvements in joint space width or bone alignment

Procedure

Delivery method:

• Single ultrasound-guided injection directly into the affected portion of the patellar tendon

The patients were split into 2 groups of 10.

• One group received the BM-MSC’s and one group received Lp-PRP

Cell Type Used

• Autologous BM-MSCs (Bone Marrow-Derived Mesenchymal Stromal Cells from the patients own body)
• Compared against leukocyte-poor Platelet-Rich Plasma (Lp-PRP)

How Cells Were Prepared

Source:

• Doctors used a needle to draw bone marrow from the back of the hip, where it’s safe and easy to access a good supply of stem cells.

Processing:

• MSCs were isolated and culture-expanded ex vivo in a GMP facility
• Expansion occurred over ~2–3 weeks

Dose:

• 20 million viable MSCs (2 × 10⁷) per injection

Positive markers:

• CD73, CD90, CD105. These markers confirm the cells are true mesenchymal stem cells (One thing to note is strictly, the ISCT says that true mesenchymal stem cells must have all three markers: CD73, CD90, and CD105.)

Full Results

Follow-up Duration:

• 12 months

Structural Healing (UTC Imaging):

• In the group that received stem cells (BM-MSC), the amount of healthy, organized tendon tissue (called echo-type I) increased from 57.5% at the start to 66.9% after 12 months. A 9.4% improvement. In contrast, the PRP group started at 61.0% and slightly dropped to 60.4%, showing no real improvement.
• For damaged or disorganized tissue (echo-type III), the stem cell group improved from 20.6% down to 14.1%, a 6.5% reduction in unhealthy tendon fibers. The PRP group actually got slightly worse, going from 17.6% to 18.4% over the same time.
• This shows that stem cells clearly helped the tendon heal, while PRP had little to no effect.

Pain:

• Patients who received stem cell treatment (BM-MSC) saw their pain scores drop from 3.56 to 0.00 over 12 months, meaning they reported no pain at all by the end of the study.
• In comparison, the PRP group started with a higher pain score of 4.67, which dropped to 1.22. A meaningful improvement, but they still experienced some lingering pain after a year.

Function:

• Strength recovery (via isometric testing) improved faster and more consistently in the MSC groupS

Side Effects:

• None major reported; procedure well-tolerated

How Cells Worked

The stem cells worked by sending out healing signals that triggered the body to repair the tendon.

They didn’t turn into new tendon cells themselves

What We Don’t Know

• Cell fate not tracked. No biopsy or imaging to confirm if MSCs survived long-term
• No data on repeat dosing or long-term outcomes beyond 1 year
• Small sample size (n=10 per group) limits statistical power

Study Details

Procedure:

• Patients were randomly assigned to receive either a single injection of BMMSCs (25 million cells) or a placebo injection. Both groups also received hyaluronic acid afterward.
• All injections were done under ultrasound guidance.

Blinding:

• Double-blind (neither the patients nor the doctors knew who received the stem cells or placebo).

Follow-up:

• Patients were assessed at 6 and 12 months after treatment.

Cell Preparation and Procedure:

• BMMSCs (Bone Marrow-Derived): Bone marrow was aspirated from the patient’s hip, processed in an FDA-approved centrifuge, and then injected into the knee.
• The injection process was one-time only, performed under ultrasound guidance.

Full Results:

Primary Endpoint (WOMAC Total Score):

• The Stempeucel group showed significant improvement in the WOMAC total score (a measure of osteoarthritis symptoms) compared to the placebo group at both 6 and 12 months:

• At 6 months, the Stempeucel group experienced a significant improvement in their symptoms, with a 23.64% greater reduction in pain and stiffness compared to the placebo group, and the results were considered statistically meaningful (P < .001). The improvement could range from 14% to 33%.
• At 12 months, the Stempeucel group experienced a 45.60% greater improvement in their symptoms compared to the placebo group, with results considered statistically significant (P < .001). The improvement could range from 35% to 56%.

Secondary Endpoints:

WOMAC Subscores (Pain, Stiffness, and Physical Function):

• Significant improvements were noted in all these subscores in the Stempeucel group at both 6 months and 12 months (P < .001).

Visual Analog Scale (VAS) for Pain:

• The Stempeucel group showed improvements in pain reduction, as measured by the VAS score at both 6 months and 12 months (P < .001).

MRI Findings (T2 Mapping):

Cartilage Quality:

• Stempeucel group: No worsening of cartilage in the medial femorotibial compartment of the knee after 12 months.
• Placebo group: Significant worsening of cartilage in the same area after 12 months (P < .001).

Cartilage Volume:

• There was no significant change in cartilage volume in the Stempeucel group at 12 months.

How Cells Worked (Researcher’s View):

The researchers explained that BMMSCs help joints through anti-inflammatory and healing signals rather than turning into cartilage:

• They reduce joint inflammation.
• They secrete healing molecules (such as cytokines and growth factors) that create a healthier joint environment.
• They may support the local cells and slow further damage, but they do not directly regenerate cartilage, which was confirmed by MRI findings showing no cartilage regeneration in this study.

Adverse Events:

• No deaths were reported.
• Serious adverse events were rare (5 cases, 3.4% of patients). These events were related to injection site issues and resolved quickly.
• Common mild events included pain, swelling, or bruising at the injection site, which were more frequent with BMMSC injections compared to the placebo.

Conclusion:

This study shows that Stempeucel can safely and effectively improve knee OA symptoms, such as pain, stiffness and physical function, for up to 12 months. However, the treatment did not regenerate cartilage. The stem cells worked by reducing inflammation and sending healing signals rather than turning into new cartilage cells.

Study Details

Procedure

Delivery method

• Single intra-articular injection into the knee joint

No surgery

No repeat dosing

This approach was chosen because:

• MSCs are thought to work through local biological signaling inside the joint
• Direct joint injection allows exposure to inflamed joint tissues
• The goal was symptom relief, not structural joint reconstruction

Only one knee per patient was treated.

Cell Type & Source

• Allogeneic adipose-derived mesenchymal stem cells (ADSCs)
• Cells sourced from healthy screened donors
• Cells were not taken from the patient
• These were culture-expanded cells, not minimally processed tissue and not SVF.

Cell Preparation & Quality

Cells were manufactured under Good Tissue Practice (GTP) conditions.

Cell preparation steps:

• Donor fat collected by liposuction
• Enzymatic isolation of ADSCs
• Culture expansion under controlled laboratory conditions
• Final preparation as a sterile cell suspension in saline

Cell identity and markers:

The final product (GXCPC1) showed:

• CD90⁺ and CD105⁺ (mesenchymal stem cell markers)
• CD34⁻ and CD45⁻ (absence of blood-derived cells)
• Verified cell viability
• Confirmed tri-lineage differentiation potential in laboratory testing

Quality and safety testing included:

• Sterility testing
• Mycoplasma testing
• Endotoxin testing
• Identity, purity, potency, and stability testing

No genetic modification was performed.

Dosage

Two dose levels were tested:

• Low dose: 6.7 × 10⁶ cells
• High dose: 4 × 10⁷ cells

Each dose was delivered in 3 mL saline, as a single injection.

No repeat injections were given.

Key Results

Safety (Primary Endpoint)

Overall safety profile:

• No treatment-related serious adverse events
• No dose-limiting toxicities
• No clinically significant laboratory abnormalities related to treatment

Common treatment-related effects:

• Injection-site pain
• Mild, temporary local reactions

Serious adverse events:

• Some occurred during follow-up
• All were judged unrelated to the cell treatment

Effectiveness (Exploratory Outcomes)

Pain (WOMAC & VAS):

• Pain scores improved from baseline in both dose groups
• Improvements were more consistent in the higher-dose group
• Effects were mainly observed within the first 12–24 weeks

Function (WOMAC function subscale):

• Some improvement in daily activity and knee function
• Again, stronger trends in the higher-dose group

Quality of life (SF-12):

• Physical quality-of-life scores improved
• Mental health scores showed no meaningful change

Because there was no control group, these improvements cannot be definitively attributed to the cells.

How the Cells Worked

The study does not show that the injected cells rebuilt cartilage or permanently repaired the joint.

Instead, the researchers believe:

• The MSCs exerted anti-inflammatory and immune-modulating effects
• They likely altered the joint environment rather than becoming joint tissue themselves

In simple terms:

• The cells likely acted as temporary biological regulators
• They did not regenerate cartilage
• Structural repair was not demonstrated

Final Thoughts

What We Don’t Know (Limitations)

• Small study (11 patients)
• No placebo or sham injection
• All participants were female
• Structural cartilage changes were not measured
• Benefits beyond early follow-up remain uncertain

Researchers’ Conclusion

This Phase I study showed that intra-articular injection of allogeneic adipose-derived mesenchymal stem cells (GXCPC1) was safe and well tolerated in people with knee osteoarthritis, with early signals of pain and function improvement at higher doses. However, the study was not designed to prove effectiveness, and larger controlled trials are needed.

According to a press release by Gwoxi in May 2025 they have received approval from Taiwan Food and Drug Administration (TFDA) to initiate a Phase III clinical trial.

What they’re trying to find out

• Whether MSC therapies are effective for treating OA, particularly in terms of cartilage regeneration and symptom relief.
• Which types of MSCs, doses, and delivery approaches yield the best outcomes.
• Whether any standardized pattern exists for clinical success.
• What mechanisms underlie MSC effectiveness: differentiation vs. signaling/trophic effects.

What they found

1. Effectiveness:

• In 67% of the 35 clinical trials reviewed (about 23 trials), patients treated with MSCs experienced more than double the improvement in pain and physical function scores compared to what would typically be expected without treatment or from baseline.
• In 71% of the stem cell therapy trials (about 25 out of 35), patients reported feeling significantly better. With at least a 17-point improvement on the WOMAC scale, which is a widely used tool to measure pain, stiffness, and joint function in people with osteoarthritis.
• In about 63% of trials, MRI scans showed actual cartilage healing after stem cell therapy. Suggesting the treatment may do more than just mask symptoms; it may help repair the joint itself.
• 2 trials showed no significant improvement in either symptoms or structure.

2. Mechanism of Action:

• Mesenchymal stem cells (MSCs) help the body heal by sending out signals that reduce inflammation and encourage tissue repair. Not by turning into cartilage themselves.
• Instead of becoming new cells, they create a healing environment that supports the body’s natural regeneration process.

3. MSC Source Comparison:

• Adipose-derived MSCs (AD-MSCs): Safe, easy to harvest, promising early results; effective even in high doses.
• Bone marrow MSCs (BM-MSCs): Most used, generally effective, but outcomes vary.
• Synovium MSCs: More chondrogenic; promising results but fewer trials.
• Umbilical cord MSCs: Encouraging long-term results in small studies.
• BMAC (non-cultured): Generally less effective; did not outperform saline in some trials.

4. Dosing Insights:

• No consistent dose-response relationship. Higher cell counts did not always yield better outcomes.
• Repeated dosing performed better than a single high dose.
• The quality of the cells, the stage of the disease, and how the cells were delivered mattered more than just giving a high dose. Bigger isn’t always better if the cells are weak, or the joint is too damaged.

5. Safety:

• MSC therapies were consistently safe across all trials.
• No severe adverse events or tumor formation observed.
• Allogeneic MSCs (from donors) were well tolerated.

6. Limitations Across Trials:

• Most trials were small (only 29% had >50 patients).
• Short follow-up periods (only 5 studies had ≥3-year follow-up).
• Variable methodology, lack of standardized outcome measures, and inconsistent imaging quality.
• Cell preparation varied widely between studies, including differences in donor source (self vs. donor), culture conditions (like serum type and oxygen levels), passage number (how many times cells were grown in the lab), and final product formulation (such as the fluid used to carry the cells and the total cell dose given).

What they concluded

• MSC therapy is safe and shows promise for reducing symptoms and potentially regenerating cartilage in OA, particularly knee OA.
• Paracrine signaling (not cell differentiation) is the primary mechanism of therapeutic benefit.
• No one MSC source or dose is definitively superior, but repeated injections appear favorable.
• BMAC may not be sufficient for cartilage regeneration, especially in moderate to severe OA.

There is a need for:

• Standardized trial designs
• Larger, long-term, controlled studies
• Quality-controlled MSC products
• Better metrics for cartilage repair

What They’re Trying to Find Out

• Whether MSC therapy is effective in reducing pain and improving joint function in KOA patients.
• Which stem cell source is most effective (adipose, bone marrow, or umbilical cord).
• Whether the therapy is safe and well-tolerated.
• Whether MSC therapy contributes to cartilage repair, as assessed by MRI.
• Whether combining MSCs with other treatments (e.g., hyaluronic acid or PRP) influences outcomes.

What They Found

1. Pain Relief

Pain Reduction – Visual Analog Scale (VAS) for pain:

• Average pooled effect size at 12 months: −0.94 (after 12 months, people who received MSC therapy had substantially less pain than those who didn’t)

Effect sizes at:

• 6 months: −0.65
• 3 months: −0.50
• 1 month: −0.14 (not statistically significant)

Best pain relief came from:

• Umbilical cord-derived MSCs (at 3 and 6 months)
• Adipose-derived MSCs (ADSCs) (at 1 and 12 months)

2. Improved Function

• WOMAC, Lequesne, and LKSS scores showed statistically significant functional improvement in the MSC groups. (WOMAC looks at overall pain, stiffness, and how well the knee works day-to-day, Lequesne measures how severe the knee problem is and how much it affects daily life, and LKSS checks how well the knee moves and functions during specific activities.)
• Autologous ADSCs were most effective for joint function recovery.

3. No Structural Cartilage Regeneration

• MRI-based WORMS scores showed no significant cartilage repair, even at high doses.
• Suggests MSCs did not differentiate into cartilage in meaningful ways.

4. No Added Benefit from PRP/HA Combinations

• MSC combined with PRP or hyaluronic acid did not significantly outperform MSC alone.

5. Cell Source & Dose Matter

• Autologous ADSCs outperformed allogeneic ones.
• Higher doses (e.g., 400 million cells) correlated with stronger pain and function outcomes.
• However, no formal dose-response curve was performed.

6. Mechanism of Action

• The benefits likely came from the stem cells sending helpful signals to reduce inflammation and support healing, rather than turning into new cartilage themselves.

7. Safety

• MSC therapy was well tolerated, with no major adverse events. Some short-term swelling/pain was reported post-injection.

Limitations they identified

• The researchers point out that many of the studies didn’t follow the same standards for preparing stem cells. So in some cases, it’s unclear whether the cells were actually isolated, tested and confirmed to be true MSCs before being used.
• Many trials only tracked patients for a few months to a year, so the long-term safety and durability of MSC therapy is still unknown.

What They Were Trying to Find Out

• Do stem cell injections relieve chronic knee pain better than placebo or usual care?
• Do they improve physical functioning or quality of life?
• Are there any safety concerns (e.g., joint swelling, pain, complications)?
• Does the type of cell, preparation method, or trial quality affect the outcome?

What They Found

• At 3–6 months, MSC injections reduced pain by −0.74 cm on a 10 cm scale, and at 12 months by −0.73 cm, both with moderate certainty. However, these improvements were not clinically meaningful, as they fell below the 1.5 cm threshold patients would notice.

In Other Words: Stem cell injections for knee arthritis showed only a tiny improvement in pain too small for most people to actually feel a difference.

Note: In total, 14 trials reported short-term pain outcomes, but only 6 high-quality trials were trusted for the final conclusion.

Physical Functioning

• At 3–6 months, stem cell injections improved physical function by just +2.23 points on a 100-point scale, which is not enough to matter to patients (10 points is the minimum meaningful change). At 12 months, the improvement was larger (+19.36 points), but the evidence was uncertain and low quality, so the result may not be reliable.

Basically, function improved slightly in some lower-quality studies, but better studies showed no real benefit.

Adverse Events:

• One case required overnight hospitalization; otherwise, side effects were non-serious but more common with MSC.

What Influenced the Results?:

• When all 16 trials were pooled, it looked like MSCs helped.
• But most of those trials had biases (bad blinding, industry funding, poor design).
• When limited to only 4–7 high-quality trials, the benefits disappeared.

What they concluded

• Short-term (3–6 months): MSC injections probably do not improve pain or function in any meaningful way.
• Long-term (12 months): They still don’t significantly reduce pain, and might improve function slightly, but the evidence is weak.
• Overall, MSC injections are not supported by high-quality evidence as an effective treatment for chronic knee OA pain.

What They Were Trying to Find Out

• The study aimed to answer a few important questions:

• Do UC-MSC injections actually help?
• Are they effective at relieving pain, reducing stiffness, and improving knee function in people with osteoarthritis?

• How do they stack up against standard treatments?
• The researchers compared UC-MSCs to common alternatives like hyaluronic acid (HA) and saline injections.

• Are the benefits real and reliable?
• They wanted to know if the positive results from clinical trials were statistically significant (not just due to chance) and clinically meaningful (actually useful in real life).

• Are the results consistent and safe?
• They looked for patterns to see if UC-MSCs worked well across different studies and whether they caused any side effects.

• Were the studies themselves trustworthy?
• To judge quality, they used tools like the PEDro scale (which scores how well a study is designed), the Egger test (which checks for publication bias), and sensitivity analysis (to see if results hold up when one study is removed).

What They Found

WOMAC Scores (Pain, Stiffness, Daily Function):

• People who got UC-MSC injections had a big improvement. Their WOMAC scores dropped by 25.85 points, which means less pain and better knee function.
• This result was statistically significant (P = .001),
• But there was a lot of variation between the studies (I² = 88%), so results weren’t totally consistent.

Knee Lysholm Score (KLS – Knee Stability & Movement):

• UC-MSCs also helped people move better. Their KLS scores increased by 18.33 points, showing strong improvement in knee performance.
• This result was very strong and consistent (P < .00001, I² = 0%),
• Which means the studies agreed closely on this benefit.

Publication Bias (Egger’s Test):

• The authors checked whether only “positive” studies were published (which can skew results).
• The Egger’s test score was 0.583, showing no sign of bias in how the data was reported.

Sensitivity Analysis:

• Showed that the results were robust and stable, even when removing studies one at a time.

PEDro Quality Scores:

• Matas et al.: 10/10 (excellent quality)
• Sun et al.: 7/10 (good)
• Wang et al.: 6/10 (good)

Injection Protocols:

• Only Matas et al. used repeated injections and reported better outcomes compared to single dosing and HA.
• The other two studies likely used single injections.

Cell Preparation Details:

• The review did not provide detailed information on UC-MSCs preparation (e.g., passage number, surface markers, or lab protocols), which limits biological comparability.

What They Concluded

• Intra-articular UC-MSC injections show significant improvement in pain and function for KOA patients compared to conventional treatments.
• UC-MSCs are safe, with only transient, mild adverse effects (e.g., temporary joint pain or effusion) reported in two studies.
• Repeated injections (as in Matas et al.) may be more effective than single-dose protocols.
• Despite promising results, only three small-scale RCTs were included, all single-center, which limits generalizability.
• There is a need for larger, multi-center RCTs with standardized protocols to confirm long-term safety and efficacy.
• The study suggests UC-MSCs could become a valuable non-surgical option for managing knee osteoarthritis, but further validation is essential.

Treatment Procedure

• Two ultrasound-guided intra-articular injections (baseline and 6 months) into the knee joint. Each dose: 50 million ADMSCs, suspended in 4 mL of either autologous conditioned serum, platelet lysate, or saline.

Cell Type Used

• Adipose-derived mesenchymal stem cells (ADMSCs). Autologous (from the patient’s own fat).

How Cells Were Prepared

• Fat harvested via liposuction (“lipoharvest”) from the abdomen or thigh.
• Cells were cultured in a cleanroom to reach 100 million total dose, expanded to a max of passage 4, and tested for viability (≥90%). Meaning t least 90% of the stem cells were alive and healthy at the time of injection.
• Identity Markers: CD90+, CD105+, CD73+; CD14/19/34/45–. One thing to note is strictly, the ISCT says that true mesenchymal stem cells must have all three markers: CD73, CD90, and CD105. And markers like CD14, CD19, CD34 & CD45 should be checked to make sure they’re not present. These are proteins found on blood or immune cells, so if stem cells don’t have them, it shows the sample is clean and not mixed with the wrong types of cells
• The stem cells were frozen and stored in liquid nitrogen (around –196 °C) to keep them fresh, then carefully thawed and rinsed with saline right before injection to make sure they were safe and viable.

Full Results and Success Rates

• Pain dropped by 54% on average (NPRS: 5.2 → 2.4).
• 88% reported improvement (PGIC), with 11% feeling fully recovered.
• 70.5% reached clinically meaningful improvements across KOOS/WOMAC.
• TKR avoided in 90% of high-risk working patients.
• No serious adverse events. Mild pain, swelling, and stiffness were common but self-limiting.
• Effect consistent across age and BMI groups.
• Most improvement occurred in the first 12 months and was maintained through 24.

How Cells Worked

• The authors believe the stem cells worked mainly by calming inflammation and reducing pain signals, not by regrowing cartilage.
• The cells help by lowering harmful chemicals in the joint (like IL-1, IL-6, and TNFα) and changing immune cells to be less aggressive.
• Because even people with “bone-on-bone” arthritis felt relief, the treatment likely helped by soothing the nerves and inflammation rather than rebuilding the joint.

What We Don’t Know

• No MRI follow-up at 24 months so we don’t know if cartilage regrew or stabilized.
• No control group, can’t fully rule out placebo effect.

What They’re Trying to Find Out

• Are repeated MSC injections more effective than a single injection at reducing pain and improving knee function?
• Are repeated injections as safe as a single injection?
• What is the best treatment strategy for patients, balancing the potential for better results with any increased risks?

What They Found

Repeated Injections Were More Effective.

• While both single and repeated injections improved pain and function, repeated MSC injections provided greater improvements, especially at the 6 and 12-month follow-ups. The statistical rankings consistently showed repeated injections were the best option for improving patient scores for pain and function over the long term.

Repeated Injections Had More Minor Side Effects.

• The analysis found that repeated MSC injections were associated with a higher incidence of adverse events compared to both single injections and conventional therapy.

Most Side Effects Were Minor.

• The vast majority of adverse events reported for both groups were mild and localized, most commonly temporary pain at the injection site. Crucially, there was no significant increase in the rate of serious adverse events for either single or repeated injections.

No Structural Cartilage Regeneration

• MRI-based scores (WORMS) showed no significant evidence of cartilage repair or regeneration in either the single or repeated injection groups. This suggests the benefits came from the cells’ signaling effects, not from them physically rebuilding the joint.

Limitations they identified

• The researchers point out that the evidence should be interpreted with caution.
• The individual studies they reviewed were often small, single-center trials.
• There was also significant variability across the studies in terms of the source of the MSCs used (e.g., bone marrow vs. fat), the dosage & the control treatments, which can affect the reliability of the pooled results.