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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new method to heal ACL injuries using mesenchymal stem cells from the patient's own bone marrow. The researchers aim to determine if these cells enhance the healing of the ACL graft (a new ligament) after surgery. Individuals who have had an ACL injury in the past six months and plan to undergo surgery with a patellar tendon graft may qualify. Participants will receive either the stem cell treatment or a small incision for comparison.

As an unphased trial, this study provides a unique opportunity to contribute to groundbreaking research that could enhance ACL recovery for future patients.

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 prior data suggests that this method is safe for ACL injury treatment?

Research has shown that using stem cells from bone marrow is generally safe for people. In one study, patients who received these stem cell treatments experienced improved limb movement and balance, indicating positive results without major safety issues. Another study on dogs with joint inflammation found that these stem cells reduced swelling, supporting their safety. Additionally, clinical trials using these stem cells for joint problems have reported few side effects. This suggests the treatment is likely safe for further testing in humans. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Researchers are excited about using autologous bone marrow-derived mesenchymal stem cells (MSCs) for ACL injuries because these cells offer a regenerative approach that traditional treatments like physical therapy and surgical repair don't provide. Unlike standard treatments that focus on repair, MSCs have the potential to enhance healing by regenerating tissue, thanks to their unique ability to differentiate into various cell types. The use of a patient's own bone marrow cells reduces the risk of rejection and complications, making this approach both innovative and personalized. Additionally, injecting the MSCs directly into the ACL allograft could improve the integration and strength of the repaired ligament, potentially leading to faster and more complete recovery.

What evidence suggests that mesenchymal stem cells might be an effective treatment for ACL injury?

This trial will compare the effects of mesenchymal stem cells (MSCs) with a control sham incision for ACL injuries. Research has shown that MSCs, special cells from bone marrow, might enhance healing for ACL injuries. These cells promote the growth of new tissue that integrates effectively into the body. Early studies suggest that MSCs can transform into cells similar to those in ligaments, which is crucial for repairing ACL tears. Patients who received these cells demonstrated promising improvements in healing and recovery. Although further research is necessary, these cells could potentially enhance recovery after an ACL injury. ^{3 5 6 7 8}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/27575050/

Autologous Bone Marrow-Derived Mesenchymal Stem Cells ... CR causes stifle joint instability and contralateral CR often develops. The dog is an important model for human anterior cruciate ligament (ACL) ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04650568?term=stem%20cell%20and%20ligament&viewType=Table&rank=5

Biologic Augmentation With Mesenchymal Stem Cells in ... This study will evaluate the efficacy of biologic augmentation of ACL reconstruction with bone marrow derived mesenchymal stem cells as measured by magnetic ...

3. arthroscopyjournal.org arthroscopyjournal.org/article/S0749-8063(24)00492-4/fulltext

Anterior Cruciate Ligament Reconstruction Augmentation ... To compare outcomes after anterior cruciate ligament reconstruction (ACLR) with bone marrow aspirate concentrate (BMAC), demineralized bone matrix (DBM), and ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S2352320417300470

Anterior cruciate ligament-derived mesenchymal stromal ... ACL-MSCs are markedly different from BM-MSCs in their differentiation ability and have a high propensity to differentiate into ligament-committed cells.

5. aoj.amegroups.org aoj.amegroups.org/article/view/3934/html

Stem cell-based therapy in anterior cruciate ligament repair Recent studies have documented bone mesenchymal stem cells (BMSCs) had the higher proliferation ability comparing to ACL-derived fibroblasts (22,47). Indeed, ...

6. journals.plos.org journals.plos.org/plosone/article?id=10.1371/journal.pone.0159095

Autologous Bone Marrow-Derived Mesenchymal Stem Cells ... We investigated use of bone marrow-derived mesenchymal stem cells (BM-MSCs) to reduce systemic and stifle joint inflammatory responses in dogs with CR.

7. sciencedirect.com sciencedirect.com/science/article/pii/S0749806324004924

Anterior Cruciate Ligament Reconstruction Augmentation ... Functional outcomes including early ROM and limb symmetry were significantly improved in patients who received ACLR with BMAC, DBM, and STA.

8. arthritis-research.biomedcentral.com arthritis-research.biomedcentral.com/articles/10.1186/s13075-017-1391-0

Safety, tolerability, clinical, and joint structural outcomes of a ... Few clinical trials have investigated the safety and efficacy of mesenchymal stem cells for the management of post-traumatic osteoarthritis.