Cartilage Cell + Stem Cell Therapy for Cartilage Defects

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Daniel B. F. Saris

Must not be taking: Anticoagulants, Herbal therapies

Disqualifiers: Pregnancy, Hip deformity, Infections, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 1 day

15 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this research study it to gather information on the safety and side effects of treating cartilage defects with autologous cartilage cells mixed with allogeneic adipose-derived mesenchymal stem cells (AMSCs) in a fibrin glue.

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

The trial requires you to stop taking herbal therapies or supplements 4 weeks before joining and until the study ends. You also need to be on a stable dose of non-steroidal anti-inflammatory medications for at least 4 weeks before the trial and continue this stable dose throughout the study. If you are taking anticoagulant medications, you cannot participate in the trial.

What data supports the effectiveness of the treatment for cartilage defects?

Research suggests that using a combination of chondrons (cartilage cells in their natural environment) and mesenchymal stromal cells (a type of stem cell) in a single-step procedure can effectively repair cartilage defects. This method has shown higher regenerative capacities compared to traditional methods, and the use of fibrin glue as a carrier has been promising in supporting the growth of new cartilage similar to natural cartilage. ^{1 2 3 4 5}

Is cartilage cell and stem cell therapy for cartilage defects safe for humans?

Research on autologous chondrocyte implantation (ACI) and its variations, such as using spheroids and fibrin glue, shows that these treatments are generally safe for humans in the short to mid-term. Studies have evaluated safety aspects like genetic stability and tumor risk, and have found no significant safety concerns. ^{2 3 5 6 7}

What makes the Cartilage Cell + Stem Cell Therapy for Cartilage Defects unique compared to other treatments?

This treatment is unique because it combines chondrons (cartilage cells in their natural environment) with stem cells from fat tissue, allowing for a single-step procedure that can potentially regenerate cartilage more effectively than traditional methods. The use of fibrin glue as a carrier helps to support and deliver these cells directly to the defect site, enhancing the repair process. ^{1 2 3 5 8}

Research Team

Aaron Krych, MD

Principal Investigator

Mayo Clinic

Eligibility Criteria

This trial is for adults with specific hip cartilage defects, who can walk unassisted and have tried other treatments without success. They must not be pregnant or planning pregnancy, have a BMI under 35, no recent infections in the target hip, stable health without significant diseases like heart conditions or diabetes, and no history of certain blood disorders or cancer.

Inclusion Criteria

Can provide written informed consent and complete HIPAA documentation after the nature of the study is fully explained and prior to any study-related procedure

Persons of childbearing potential must have a negative pregnancy test prior to receiving the study drug and will agree to use adequate contraception

Fully understanding of the requirements of the study and willingness to comply with the treatment plan

Exclusion Criteria

Significant structural deformity, including large cam lesion or moderate dysplasia

I have a serious heart, brain, kidney, liver, bone, or hormone-related disease.

Tönnis Grade II or greater on X-Ray

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive the combined product of autologous cartilage cells and allogeneic AMSCs in a fibrin glue carrier

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

Multiple visits at 1-2 weeks, 6 weeks, 12 weeks, 24 weeks, 52 weeks, 18 months, and 24 months post-treatment

Treatment Details

Interventions

• Autologous Chondrocytes in their Pericellular Matrix (Chondrons) Coimplanted with Allogeneic Adipose-Derived Mesenchymal Stromal Cells (AMSCs) in a Fibrin Glue Carrier

Trial Overview The study tests a new treatment where patients' own cartilage cells are mixed with donor fat-derived stem cells and a special glue to repair damaged hip cartilage. The goal is to see if this mix is safe and what side effects it might cause when used to treat cartilage defects in the hip.

Participant Groups

Group I: CartiLage Auto/Allo IMplantation for Focal Hip Cartilage Defects Experimental Treatment 1 Intervention

Subject will receive the combined product of autologous cartilage cells and allogeneic AMSCs in a fibrin glue carrier.

Autologous Chondrocytes in their Pericellular Matrix (Chondrons) Coimplanted with Allogeneic Adipose-Derived Mesenchymal Stromal Cells (AMSCs) in a Fibrin Glue Carrier is already approved in United States, European Union for the following indications:

Approved in United States as MACI for:

• Symptomatic, single or multiple full-thickness cartilage defects of the knee with or without bone involvement in adults

Approved in United States as Carticel for:

• Symptomatic cartilaginous defects of the femoral condyle (medial, lateral or trochlear) caused by acute or repetitive trauma

Approved in European Union as Autologous Chondrocyte Implantation for:

• Cartilage defects of the knee

Who Is Running the Clinical Trial?

Daniel B. F. Saris

Lead Sponsor

Trials

1

Recruited

20+

Findings from Research

The combination of chondrons and mesenchymal stromal cells (MSCs) significantly enhances cartilage matrix production, leading to better cartilage regeneration compared to traditional methods, as shown in both in vitro studies and animal models.

In a goat model, this innovative single-step procedure using chondrons and MSCs resulted in superior cartilage repair outcomes compared to the standard microfracture technique, indicating its potential as a more effective treatment for focal cartilage lesions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single-stage cell-based cartilage regeneration using a combination of chondrons and mesenchymal stromal cells: comparison with microfracture. Bekkers, JE., Tsuchida, AI., van Rijen, MH., et al.[2013]

In a study involving 32 goats, the sutured cell-seeded collagen matrix technique for autologous chondrocyte implantation (ACI) showed similar effectiveness in repairing cartilage defects compared to traditional ACI methods.

Using glue to secure the cell-seeded membrane resulted in inferior repair outcomes, suggesting that suturing is the preferred method for optimizing cartilage repair in ACI procedures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In Vivo Evaluation of Different Surgical Procedures for Autologous Chondrocyte Implantation. Maréchal, M., Van Hauwermeiren, H., Neys, J., et al.[2018]

Matrix-associated autologous chondrocyte implantation (ACI) using spheroids is a safe and effective treatment for medium to large cartilage defects in the knee, showing significant improvement in patient-reported outcomes (KOOS) from a baseline score of 57.0 to 76.9 at 5 years.

The treatment demonstrated consistent efficacy across different defect locations and sizes, with a low treatment failure rate of 4% over 5 years, and most adverse events occurring within the first year, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Matrix-Associated Autologous Chondrocyte Implantation With Spheroids for Patellofemoral or Tibiofemoral Defects: A 5-Year Follow-up of a Phase 2, Dose-Confirmation Trial. Hoburg, A., Niemeyer, P., Laute, V., et al.[2022]

Autologous chondrocyte implantation (ACI) can lead to both repair and regeneration of damaged cartilage, as evidenced by the presence of newly synthesized type II collagen in biopsy samples from patients 9-30 months post-surgery.

The study revealed active remodeling at the graft site, with significant enzymatic activity indicating both degradation and synthesis of cartilage matrix components, suggesting that ACI promotes a dynamic healing process.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Matrix turnover in human cartilage repair tissue in autologous chondrocyte implantation. Roberts, S., Hollander, AP., Caterson, B., et al.[2019]

Autologous chondrocyte implantation (ACI) using fibrin glue has shown promising results in treating deep articular cartilage defects, with the newly formed cartilage exhibiting biomechanical properties similar to natural cartilage.

In a study involving 50 patients, the ACI technique effectively utilized the patient's own cells and fibrin glue as a carrier, suggesting it could be a viable option for cartilage repair in the knee.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chondrocyte suspension in fibrin glue. Wysocka, A., Mann, K., Bursig, H., et al.[2011]

Autologous chondrocyte implantation (ACI) using spheroids of chondrocytes shows promising short- to mid-term safety and efficacy for treating focal cartilage defects, based on a systematic review of 20 studies, including both preclinical and clinical research.

The preclinical studies ensured the quality and safety of the ACI product by evaluating factors like biodistribution and tumorigenicity, supporting its use in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of Matrix-Associated Autologous Chondrocyte Implantation with Spheroids in the Treatment of Large Chondral Defects in the Knee: A Systematic Review. Vonk, LA., Roël, G., Hernigou, J., et al.[2021]

In a study of 13 patients undergoing autologous chondrocyte implantation (ACI) for knee cartilage defects, T2 mapping showed significant improvement in graft maturation over 36 months, with T2 relaxation times decreasing from 41.6 milliseconds at 6 months to 30.9 milliseconds at 36 months, indicating that the grafts were maturing to resemble healthy cartilage.

Despite the positive changes in T2 relaxation times, there was no correlation found between the clinical outcomes measured by the International Knee Documentation Committee (IKDC) scores and the T2 values, suggesting that improvements in graft maturation do not necessarily translate to better clinical performance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Graft maturation of autologous chondrocyte implantation: magnetic resonance investigation with T2 mapping. Niethammer, TR., Safi, E., Ficklscherer, A., et al.[2022]

The study analyzed cells from autologous chondrocyte implantation (ACI) repair tissues in two patients several years after treatment, revealing that ACI repair cells have a mixed appearance and characteristics similar to both chondrocytes and mesenchymal stromal/stem cells (MSCs).

ACI repair cells showed faster proliferation than MSCs but slower than normal chondrocytes, indicating that while they can grow well, their differentiation capacity aligns more closely with MSCs, suggesting a unique role in cartilage repair.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characterization of the cells in repair tissue following autologous chondrocyte implantation in mankind: a novel report of two cases. Wright, KT., Mennan, C., Fox, H., et al.[2022]

References

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

Single-stage cell-based cartilage regeneration using a combination of chondrons and mesenchymal stromal cells: comparison with microfracture. [2013]

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

In Vivo Evaluation of Different Surgical Procedures for Autologous Chondrocyte Implantation. [2018]

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

Safety and Efficacy of Matrix-Associated Autologous Chondrocyte Implantation With Spheroids for Patellofemoral or Tibiofemoral Defects: A 5-Year Follow-up of a Phase 2, Dose-Confirmation Trial. [2022]

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

Matrix turnover in human cartilage repair tissue in autologous chondrocyte implantation. [2019]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Chondrocyte suspension in fibrin glue. [2011]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Role of Matrix-Associated Autologous Chondrocyte Implantation with Spheroids in the Treatment of Large Chondral Defects in the Knee: A Systematic Review. [2021]

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

Graft maturation of autologous chondrocyte implantation: magnetic resonance investigation with T2 mapping. [2022]

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

Characterization of the cells in repair tissue following autologous chondrocyte implantation in mankind: a novel report of two cases. [2022]