Mesenchymal Stem Cell Augmentation for ACL Injury

(BMAC Trial)

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: Rush University Medical Center

Must not be taking: Anticoagulants, Immunosuppressants, Systemic steroids

Disqualifiers: Knee surgery, Cancer, HIV, others

Compensation: Varies

Number of Visits: 8

Duration: Immediate post-surgery

100 Participants Needed

Trial Summary

Do I need to stop taking my current medications for the trial?

The trial protocol does not specify whether you need to stop taking your current medications. However, if you are taking medications that increase the risk of bleeding or infection, such as anticoagulants or immunosuppressants, you may not be eligible to participate.

What data supports the effectiveness of the treatment Autologous Bone Marrow Derived Mesenchymal Stem Cells for ACL injury?

Research shows that mesenchymal stem cells (MSCs) can help repair damaged tissues, and studies suggest that MSCs from the ACL and bone marrow have similar healing properties. In animal models, injecting MSCs into partially torn ACLs has been shown to speed up healing, indicating potential benefits for human ACL injuries. ^{1 2 3 4 5}

Is the use of mesenchymal stem cells generally safe for humans?

Research shows that mesenchymal stem cells (MSCs) are generally safe for humans, with most adverse events being mild, such as temporary knee swelling and pain. In a review of studies, only a small number of severe cases required overnight hospitalization, indicating a low risk of serious side effects. ^{4 6 7 8 9}

How is the treatment with autologous bone marrow-derived mesenchymal stem cells for ACL injury different from other treatments?

This treatment is unique because it uses the patient's own bone marrow-derived mesenchymal stem cells, which are injected directly into the knee joint to promote healing of the ACL. Unlike other treatments, it leverages the body's natural regenerative capabilities without the need for a culture system, making it easier to apply in a clinical setting. ^{1 2 5 10 11}

What is the purpose of this trial?

This study will evaluate the efficacy of biologic augmentation of ACL reconstruction with bone marrow derived mesenchymal stem cells as measured by magnetic resonance imaging to detect graft healing and integration. Secondary endpoints will include validated patient reported outcome measures, as well as functional outcome using objective examination findings.

Eligibility Criteria

This trial is for English-speaking adults aged 18-60 with a recent ACL injury who are getting patellar tendon allograft reconstruction. Candidates must be able to follow up and have an MRI. Excluded are those with HIV, hepatitis, prior knee surgery, psychiatric illnesses affecting study comprehension or follow-up, other ligament injuries, cancer (unless in long-term remission), substance abuse issues, pregnancy or breastfeeding women, and anyone at risk of bleeding or infection.

Inclusion Criteria

I am between 18 and 60 years old and need ACL surgery within 6 months of injury using a patellar tendon from a donor.

Written informed consent is obtained

Exclusion Criteria

I have a ligament injury alongside my main condition.

I haven't had PRP or similar treatments for my knee in the last year.

I am not pregnant or breastfeeding and agree to use birth control during the study.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients undergo ACL reconstruction with or without BMAC treatment

Immediate post-surgery

1 visit (in-person)

Early Follow-up

Initial follow-up to assess early graft healing and integration

6 weeks

1 visit (in-person)

Intermediate Follow-up

Assessment of graft healing and patient outcomes at 3 and 6 months

6 months

2 visits (in-person)

Long-term Follow-up

Continued monitoring of graft maturation and patient outcomes

24 months

4 visits (in-person)

Treatment Details

Interventions

• Autologous Bone Marrow Derived Mesenchymal Stem Cells

Trial Overview The study tests if injecting one's own bone marrow-derived mesenchymal stem cells into the reconstructed ACL improves healing compared to a sham procedure. Healing is monitored via MRI scans and patient-reported outcomes alongside objective functional assessments.

Participant Groups

Group I: Mesenchymal Stem Cell Recipient Experimental Treatment 1 Intervention

Patients in this group will receive between 1-4 ml of bone marrow aspirate concentrate (BMAC) containing mesenchymal stem cells (MSCs) obtained from their iliac crest. A small incision will be made on the anterior superior iliac spine in order to withdraw the aspirate. The aspirate will be ran through a centrifuge in order to isolate the BMAC containing MSCs. The BMAC will be injected into the ACL allograft prior to implanting into the patient.

Group II: Control Sham Incision Placebo Group 1 Intervention

Patients will receive a sham incision on the anterior superior iliac spine where the bone marrow aspirate is obtained in the the experimental group. This ensures proper blinding. The patient will receive the normal standard of care.

Who Is Running the Clinical Trial?

Rush University Medical Center

Lead Sponsor

Trials

448

Recruited

247,000+

Findings from Research

In a small case series of 10 patients with ACL tears, 70% showed objective improvements in ligament integrity after receiving an injection of autologous bone marrow concentrate, suggesting this treatment may enhance healing.

Patients reported significant improvements in knee function, with a mean increase of 23.3 points on the Lower Extremity Functional Scale, indicating that this treatment could be effective for managing ACL injuries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anterior cruciate ligament tears treated with percutaneous injection of autologous bone marrow nucleated cells: a case series. Centeno, CJ., Pitts, J., Al-Sayegh, H., et al.[2020]

References

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

Mesenchymal Stem Cells Isolated from the Anterior Cruciate Ligament: Characterization and Comparison of Cells from Young and Old Donors. [2022]

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

Intra-articular injection of mesenchymal stromal cells in partially torn anterior cruciate ligaments in a rat model. [2022]

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

Mesenchymal stem cell characteristics of human anterior cruciate ligament outgrowth cells. [2022]

4. New Zealand pubmed.ncbi.nlm.nih.gov

Anterior cruciate ligament tears treated with percutaneous injection of autologous bone marrow nucleated cells: a case series. [2020]

5. Germany pubmed.ncbi.nlm.nih.gov

Post injury changes in the properties of mesenchymal stem cells derived from human anterior cruciate ligaments. [2021]

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

Safety, tolerability, clinical, and joint structural outcomes of a single intra-articular injection of allogeneic mesenchymal precursor cells in patients following anterior cruciate ligament reconstruction: a controlled double-blind randomised trial. [2022]

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

Acute mobilization and migration of bone marrow-derived stem cells following anterior cruciate ligament rupture. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Outcomes of human umbilical cord blood-derived mesenchymal stem cells in enhancing tendon-graft healing in anterior cruciate ligament reconstruction: an exploratory study. [2021]

9. 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]

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

New strategies for anterior cruciate ligament partial rupture using bone marrow transplantation in rats. [2022]

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

Impact of chronicity of injury on the proportion of mesenchymal stromal cells derived from anterior cruciate ligaments. [2018]