The safety and efficacy of magnetic targeting using autologous mesenchymal stem cells for cartilage repair
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A new cell delivery system using magnetic force, termed magnetic targeting, was developed for the accumulation of locally injected cells in a lesion. The aim of this study was to assess the safety and efficacy of mesenchymal stem cell (MSC) magnetic targeting in patients with a focal articular cartilage defect in the knee.
MSC magnetic targeting for five patients was approved by the Ministry of Health Labour and Welfare of Japan. Autologous bone marrow MSCs were cultured and subsequently magnetized with ferucarbotran. The 1.0-T compact magnet was attached to a suitable position around the knee joint to allow the magnetic force to be as perpendicular to the surface of the lesion as possible. Then 1 × 107 MSCs were injected into the knee joint. The magnet was maintained in the same position for 10 min after the MSC injection. The primary endpoint was the occurrence of any adverse events. The secondary endpoints were efficacy assessed by magnetic resonance imaging (MRI) T2 mapping and clinical outcomes using the International Knee Documentation Committee (IKDC) Subjective Knee Evaluation and the Knee Injury and Osteoarthritis Outcome Score (KOOS).
No serious adverse events were observed during the treatment or in the follow-up period. Swelling of the treated knee joint was observed from the day after surgery in three of the five patients. The swelling resolved within 2 weeks in two patients. MRI showed that the cartilage defect areas were almost completely filled with cartilage-like tissue. MOCART scores were significantly higher 48 weeks postoperatively than preoperatively (74.8 ± 10.8 vs 27.0 ± 16.8, p = 0.042). Arthroscopy in three patients showed complete coverage of their cartilage defects. Clinical outcome scores were significantly better 48 weeks postoperatively than preoperatively for the IKDC Subjective Knee Evaluation (74.8 ± 17.7 vs 46.9 ± 17.7, p = 0.014) and knee-related quality-of-life (QOL) in the KOOS (53.8 ± 26.4 vs 22.5 ± 30.8, p = 0.012).
Magnetic targeting of MSCs was safely performed and showed complete coverage of the defects with cartilage-like tissues and significant improvement in clinical outcomes 48 weeks after treatment. The magnetic targeting of MSCs is useful as a minimally invasive treatment for cartilage repair.
Level of evidence
KeywordsCartilage regeneration Mesenchymal stem cell Cell transplantation Magnet Clinical outcome
Osteochondral autograft transfer
Autologous chondrocyte implantation
Mesenchymal stem cell
Magnetic resonance imaging
International Knee Documentation Committee
Knee Injury and Osteoarthritis Outcome Score
Quality of life
Activities of daily living
Magnetic resonance observation of cartilage repair tissue
Intraclass correlation coefficient
NK designed the clinical trial and conducted the MSC culture and data analysis. MO was the chief investigator of the study, designed the fundamental concept of magnetic targeting, performed the arthroscopic procedures, and followed up the patients. NA performed the arthroscopic procedures and followed up the patients. MI handled the MSC culture and quality examinations of the MSCs. SY and LSL assisted with the design of the clinical trial. GK and TK performed the preclinical studies before starting the clinical trial, and assisted with the arthroscopic procedures. All authors wrote, edited, and approved the manuscript.
This study was supported by the Research Project for Practical Applications of Regenerative Medicine to MO from Japan Agency for Medical Research and Development.
Compliance with ethical standards
Conflict of interest
The authors declare no competing interests.
The protocol of this clinical trial received scientific and ethical regulatory review, and was approved by the Ministry of Health, Labour and Welfare of Japan.
All patients provided written informed consent before participation in the trial, collection of the bone marrow aspirate, and surgery, respectively.
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