Mesenchymal Stem Cells for Knee Osteoarthritis

Overseen By James E Voos, MD

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: University Hospitals Cleveland Medical Center

Must not be taking: Immunosuppressants

Disqualifiers: Obesity, Cardiac disease, Neurologic, Psychiatric, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 7

Duration: 1 day

16 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, if you are on medications for active cardiac or respiratory disease, or if you are on immunosuppressive medications, you may not be eligible to participate.

What data supports the effectiveness of the treatment for knee osteoarthritis?

Research shows that using adipose-derived mesenchymal stem cells (ADMSCs) for knee osteoarthritis can significantly reduce pain and improve joint function. Studies found that patients receiving these stem cell injections experienced better outcomes compared to those who did not, with improvements lasting up to 12 months. ^{1 2 3 4 5}

Is the use of mesenchymal stem cells for knee osteoarthritis safe?

Research shows that using mesenchymal stem cells, including those derived from adipose tissue, for treating knee osteoarthritis is generally safe. Most studies report no serious adverse events, with some patients experiencing temporary knee pain and swelling after injection. ^{1 6 7 8 9}

How is autologous mesenchymal stem cell therapy different from other treatments for knee osteoarthritis?

Autologous mesenchymal stem cell therapy for knee osteoarthritis is unique because it uses the patient's own stem cells, derived from fat tissue, to potentially relieve pain and improve joint function by regenerating damaged cartilage, unlike traditional treatments that mainly focus on symptom relief. ^{1 5 10 11 12}

What is the purpose of this trial?

Many patients with osteoarthritis of the knee fail non-operative measures and elect to have knee arthroplasty to improve their quality of life. If successful, intra-articular mesenchymal stem cell (MSC) injections into the knee may offer another viable non-operative treatment modality. Additionally, this modality may have reparative or regenerative potential, which could lead to the first treatment for osteoarthritis that treats the underlying disease as opposed to symptomatic control. Additionally, there are no acceptable non-surgical treatments for focal chondral defects of the knee. Surgical treatments that do exist have diminished outcomes if performed on patients older than age 30-40 years. If successful, intra-articular MSC injections into the knee would represent the first non-operative treatment for focal chondral defects and also represent a potential option for treatment in patients over the age of 30-40 years. This trial will be a prospective, single-center phase I pilot study to evaluate the safety and tolerability of a single intra-articular injection of autologous bone marrow-derived MSCs in 16 subjects, 8 who have knee osteoarthritis and 8 who have a focal chondral defect in the knee. Patients will undergo a bone marrow harvest procedure at the Dahms Clinical Research Unit (DCRU) of University Hospitals Cleveland Medical Center. MSCs will be isolated and expanded. After approximately 2-3 weeks, patients will return for an intra-articular injection of 50x106 MSCs Subsequent study visits will occur on post-injection day 7 and months 2, 6, 12, and 24. Safety of intra-articular injection of MSCs will be evaluated at study visits by interval history, physical examination and assessment of any adverse events that are observed/reported. Additionally, efficacy will be evaluated by having patients complete functional outcome measures including: Visual Analog Score (VAS) for pain, Knee Injury and Osteoarthritis Outcome Score (KOOS), International Knee Documentation Committee (IKDC) Subjective Knee Form, and Lysholm Knee Scale. These will be completed at the pre-treatment visit and then repeated at the 2, 6, 12, and 24-month follow-up visits. Lastly, T1 rho and T2 mapping on magnetic resonance imaging (MRI) will be used to assess for improved cartilage quality after intra-articular injection of MSCs. An MRI will be obtained at the pre-treatment visit. At the 12 and 24 month follow up visit, additional MRIs will be obtained and analyzed to compare the pre-treatment MRI to post-treatment MRIs.

Research Team

James Voos, MD

Principal Investigator

University Hospitals Cleveland Medical Center

Eligibility Criteria

Adults aged 18-60 with knee osteoarthritis or a focal chondral defect in the knee, who have not found relief through non-invasive treatments. Participants must be able to consent and women of childbearing age should agree to effective contraception or abstinence. Exclusions include severe arthritis stage, major limb misalignment, concurrent serious conditions (like heart disease), high BMI (>40), mental illness affecting study compliance, recent major surgery, immunosuppression, cancer history, MRI contraindications like pacemakers, certain blood disorders and allergies.

Inclusion Criteria

I have had knee pain in one knee for more than 4 months.

My condition did not improve with non-surgical treatments.

You have signs of mild to moderate wear and tear on your joint cartilage seen in imaging tests like MRI or X-rays.

Exclusion Criteria

I haven't had major surgery except for diagnosis in the last 4 weeks.

Criterion: You cannot have certain metal implants in your body, low levels of certain blood cells, a history of allergic reactions to Dimethyl sulfoxide (DMSO), recent treatment for alcohol or drug abuse, or any major health changes in the last 2 weeks.

My knee pain is due to severe arthritis.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-3 weeks

Bone Marrow Harvest

Patients undergo a bone marrow harvest procedure at the Dahms Clinical Research Unit

1 day

1 visit (in-person)

Treatment

Intra-articular injection of 50x10^6 MSCs after MSCs are isolated and expanded

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment with follow-up visits at 7 days, 2, 6, 12, and 24 months

24 months

5 visits (in-person)

Treatment Details

Interventions

• Autologous Mesenchymal Stem Cells

Trial Overview The trial is testing whether injecting one's own mesenchymal stem cells into the knee can help treat osteoarthritis or cartilage injuries without surgery. It's a phase I pilot study where participants will receive an injection after their stem cells are harvested and grown. They'll be monitored over two years for safety and improvements in pain and joint function using physical exams and questionnaires.

Participant Groups

Group I: Osteoarthritis Experimental Treatment 1 Intervention

The OA subgroup will be patients aged 18-60 years who have chronic knee pain due to early OA that have not responded to conservative, non-invasive measures such as physical therapy, medications, and activity modification.

Group II: Cartilage Experimental Treatment 1 Intervention

The focal chondral defect subgroup will be patients aged 18-60 years who participate in recreational or professional sports and are symptomatic from a focal chondral defect shown on MRI.

Who Is Running the Clinical Trial?

University Hospitals Cleveland Medical Center

Lead Sponsor

Trials

348

Recruited

394,000+

Case Western Reserve University

Collaborator

Trials

314

Recruited

236,000+

Findings from Research

In a study involving 30 participants with knee osteoarthritis, autologous adipose-derived mesenchymal stem cell (ADMSC) therapy was found to be safe, with no serious adverse events reported.

Both treatment groups receiving ADMSC injections showed significant improvements in pain and function after 12 months, and MRI results suggested that the therapy may help slow down disease progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adipose-derived mesenchymal stem cell therapy in the treatment of knee osteoarthritis: a randomized controlled trial. Freitag, J., Bates, D., Wickham, J., et al.[2019]

The study evaluated the safety of intra-articular injections of adipose-derived stromal cells (ASCs) in 18 patients with severe knee osteoarthritis (OA) and found no serious adverse events, indicating that the treatment is safe.

Patients receiving low-dose ASCs reported significant improvements in pain and function after 6 months, suggesting potential efficacy, although further controlled studies are needed to confirm these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adipose Mesenchymal Stromal Cell-Based Therapy for Severe Osteoarthritis of the Knee: A Phase I Dose-Escalation Trial. Pers, YM., Rackwitz, L., Ferreira, R., et al.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Adipose-derived mesenchymal stem cell therapy in the treatment of knee osteoarthritis: a randomized controlled trial. [2019]

2. England pubmed.ncbi.nlm.nih.gov

The role of adipose-derived mesenchymal stem cells in knee osteoarthritis: a meta-analysis of randomized controlled trials. [2023]

3. Germany pubmed.ncbi.nlm.nih.gov

Autologous micro-fragmented adipose tissue injection provides significant and prolonged clinical improvement in patients with knee osteoarthritis: a case-series study. [2023]

4. Germany pubmed.ncbi.nlm.nih.gov

Patients with stage II of the knee osteoarthritis most likely benefit from the intra-articular injections of autologous adipose tissue-from 2 years of follow-up studies. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Clinical and laboratory findings following transplantation of allogeneic adipose-derived mesenchymal stromal cells in knee osteoarthritis, a brief report. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Safety Studies for Use of Adipose Tissue-Derived Mesenchymal Stromal/Stem Cells in a Rabbit Model for Osteoarthritis to Support a Phase I Clinical Trial. [2020]

7. England pubmed.ncbi.nlm.nih.gov

Intra-Articular Injection of Autologous Adipose Tissue-Derived Mesenchymal Stem Cells for the Treatment of Knee Osteoarthritis: A Phase IIb, Randomized, Placebo-Controlled Clinical Trial. [2020]

8. United States pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Cultured/Noncultured Mesenchymal Stromal Cells without Concurrent Surgery for Knee Osteoarthritis: A Systematic Review of Randomized Controlled Trials. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Adipose Mesenchymal Stromal Cell-Based Therapy for Severe Osteoarthritis of the Knee: A Phase I Dose-Escalation Trial. [2022]

10. England pubmed.ncbi.nlm.nih.gov

Autologous stem cell therapy in knee osteoarthritis: a systematic review of randomised controlled trials. [2022]

11. England pubmed.ncbi.nlm.nih.gov

Repeated intra-articular injection of allogeneic mesenchymal stem cells causes an adverse response compared to autologous cells in the equine model. [2018]

12. England pubmed.ncbi.nlm.nih.gov

Intra-articular injection of autologous adipose-derived mesenchymal stem cells in the treatment of knee osteoarthritis. [2019]