Orthopedic Surgery

Aug. 29, 2023

This Q&A features Daniel B. F. Saris, M.D., Ph.D., an orthopedic surgeon specializing in knee surgery with a focus on cell-based surgical regenerative medicine at Mayo Clinic's campus in Minnesota. Here, he explains a regenerative medicine procedure for joint restoration that he believes addresses an unmet need. Dr. Saris discusses its background and future, and appropriate referral candidates.

What is the joint restoration procedure Mayo Clinic investigators are working on?

A team of Mayo Clinic orthopedic and regenerative medicine researchers has continued development and testing of a knee joint restoration procedure, called recycled cartilage auto/allo implantation (RECLAIM). I brought RECLAIM with me from the University Medical Center Utrecht in the Netherlands, where we developed this procedure and called it IMPACT.

In this procedure, we debride the patient's knee defect. We remove cartilage from the knee or hip, mincing these pieces into smaller fragments and extracting cartilage cells through chemical digestion to the level of the chondron. We combine these recycled autologous chondrons with allogeneic donor mesenchymal stem cells (MSCs). The mixture of 10% to 20% of the patient's cells with 80% to 90% MSCs is placed into fibrin glue, which allows the surgeon to inject them into the patient's knee defect. This procedure enables the patient's body to repair the cartilage defect, something it otherwise would be unable to do.

RECLAIM is a one-stage innovative procedure for hip and knee that enables tissue growth and restoration of cartilage in the patient's joint. Within one year, the defect is filled. DNA analysis has shown this to be patient-derived new cartilage tissue without donor DNA remaining. I see it as the MSCs providing both immune modulatory signals as well as growth factor, reminding the cartilage to grow. Ultimately, RECLAIM may help preserve the joint by filling the "pothole" for a better "drive."

We have learned that combining native cartilage cells and allogeneic MSCs can be a good partnership. We consider the transplant successful if the joint is still viable in 13 to 20 years.

When did RECLAIM become available?

RECLAIM for hip and knee is performed under FDA scrutiny as an investigational new drug in a phase 1 trial I led with a team of Mayo Clinic investigators, and it is not yet widely available. The trial began in September 2018 and ends in September 2024.

What patients are eligible for RECLAIM?

Indications for this therapy are precise. The patient must meet the following criteria:

• Fresh, symptomatic cartilage defects.
• Nonarthritic joints.
• Injury due to sports or lifestyle.
• Age 18 to 55.

Often, these cartilage defects are from trauma or athletic injury.

What inspires your involvement in this research?

One of my biggest drivers is improving quality of life. People need to move in their lives and they need their joints to work. Patients' alternatives are usually to deal with discomfort or quit sports. We want to help them return to sports or their pre-injury lifestyles.

I am also passionate about helping patients with arthritis, one of the biggest quality-of-life threats.

My research team specifically is seeking solutions to treat defects in young patients with active lifestyles. This is a growing group, and age limits are changing. Someday, if people live to age 120, we need joint preservation solutions for individuals ages 30 to 60 and older.

Does RECLAIM treat joints or cartilage injuries other than in the knee and hip?

We hope it will work with other joints, but that has not been studied yet. The need seems greatest for hip and knee, but we would like to explore hand, ankle, elbow and others.

We also hope RECLAIM will apply to the meniscus. We have a Ph.D. program working on that potential application.

Are there current clinical trials using RECLAIM?

Aaron J. Krych, M.D., an orthopedic surgeon at Mayo Clinic in Minnesota, is leading a phase 1 RECLAIM study in the hip joint. It's open for patient enrollment. We are doing a randomized controlled trial in the Netherlands for permission to enter this as standard of care.

How did your research transition from the Netherlands to the United States?

Lucienne Vonk, Ph.D., and I developed the idea from the first experiments through completing the initial human trials. Dr. Vonk serves as a senior researcher in the Department of Orthopaedics, University Medical Center Utrecht, the Netherlands, and director of musculoskeletal diseases at Xintela AB, a biomedical company in Sweden. As we were working with RECLAIM in the Netherlands, evidence and international enthusiasm grew. It was showing promise. Mayo Clinic orthopedic and regenerative medicine leadership gave us the opportunity to continue developing RECLAIM using Mayo Clinic's stem cell bank and conduct U.S. RECLAIM clinical trials.

Also important to me was that Mayo Clinic had orthopedic surgeons who could perform the RECLAIM procedure and that Mayo had the brand respect needed to make a clinical trial happen in the U.S.

Why should I send my patients to Mayo Clinic for this procedure?

First, we will take good care of your patients. Second, it is a cell-based cartilage repair in a single surgical procedure and only available at Mayo Clinic in Minnesota in the U.S. Outside of the United States, it's also available at University Medical Center Utrecht.

If patients have cartilage defects, say, in the knee, they often have pain and swelling clinically, and the defect can be visible on MRI. Mayo Clinic has a specialized cartilage clinic. In the knee clinic, we jointly analyze those injuries with the whole team to develop one-visit solutions.

Mayo Clinic also has world leaders in orthopedic injectable therapy if our experts deem injectables best for patients' injuries.

We also have significant multidisciplinary expertise available at Mayo Clinic and have numerous clinical trials to offer.

If you have a question regarding sending a patient to Mayo Clinic, contact knee@mayo.edu or cartilage@mayo.edu.

What are examples of your research team's goals?

We attempted a moonshot effort to put all elements of this procedure into one arthroscopic surgery, an important goal for our team. To now see that come to fruition after some years is exciting and rewarding for the team, and hopefully it is a valuable improvement for our patients.

Ultimately, we want RECLAIM to be available widely for many patients and to be able to apply this cell-cell combination for other joint challenges and even other organs.

For more information

Clinical trials: REcycled CartiLage Auto/Allo Implantation. Mayo Clinic.

Refer a patient to Mayo Clinic.