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Knee Surgery, Sports Traumatology, Arthroscopy

, Volume 26, Issue 12, pp 3626–3635 | Cite as

The safety and efficacy of magnetic targeting using autologous mesenchymal stem cells for cartilage repair

  • Naosuke Kamei
  • Mitsuo OchiEmail author
  • Nobuo Adachi
  • Masakazu Ishikawa
  • Shinobu Yanada
  • L. Scott Levin
  • Goki Kamei
  • Takaaki Kobayashi
Knee

Abstract

Purpose

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.

Methods

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).

Results

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).

Conclusion

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

IV.

Keywords

Cartilage regeneration Mesenchymal stem cell Cell transplantation Magnet Clinical outcome 

Abbreviations

OAT

Osteochondral autograft transfer

ACI

Autologous chondrocyte implantation

MSC

Mesenchymal stem cell

MRI

Magnetic resonance imaging

IKDC

International Knee Documentation Committee

KOOS

Knee Injury and Osteoarthritis Outcome Score

QOL

Quality of life

ADL

Activities of daily living

MOCART

Magnetic resonance observation of cartilage repair tissue

ICC

Intraclass correlation coefficient

SD

Standard deviation

Notes

Author contributions

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.

Funding

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.

Ethical approval

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.

Informed consent

All patients provided written informed consent before participation in the trial, collection of the bone marrow aspirate, and surgery, respectively.

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Copyright information

© European Society of Sports Traumatology, Knee Surgery, Arthroscopy (ESSKA) 2018

Authors and Affiliations

  1. 1.Department of Orthopaedic Surgery, Division of Medicine, Biomedical Sciences Major, Graduate School of Biomedical ScienceHiroshima UniversityHiroshimaJapan
  2. 2.Medical Center for Translational and Clinical ResearchHiroshima University HospitalHiroshimaJapan
  3. 3.Hiroshima UniversityHigashihiroshimaJapan
  4. 4.Japan Tissue Engineering Co. LtdGamagoriJapan
  5. 5.Department of Orthopaedic SurgeryUniversity of PennsylvaniaPhiladelphiaUSA
  6. 6.Department of Orthopaedic SurgeryHiroshima Prefectural HospitalHiroshimaJapan
  7. 7.Department of Orthopaedic SurgeryTsuchiya General HospitalHiroshimaJapan

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