Arthroscopic Transplantation of Synovial Stem Cells Improves Clinical Outcomes in Knees With Cartilage Defects.
BACKGROUND
Transplantation of mesenchymal stem cells (MSCs) is one possible strategy to achieve articular cartilage repair. We previously reported that synovial MSCs were highly proliferative and able to undergo chondrogenesis. We also found that placing a suspension of synovial MSCs on a cartilage defect for 10 minutes promoted cartilage repair in rabbit and pig models. However, the in vivo efficacy of this approach has not been tested clinically.


OBJECTIVE
We asked whether transplantation of synovial MSCs improves (1) MRI features, (2) histologic features, and (3) clinical evaluation scores in patients with cartilage defects in the knee?


METHODS
Patients with a symptomatic single cartilage lesion of the femoral condyle were indicated for inclusion in our study, and between April 2008 and April 2011, 10 patients were enrolled in this study. All patients completed followups of 3 years or more. The average followup period was 52 months (range, 37-80 months). Synovial MSCs were expanded with 10% autologous human serum for 14 days after digestion. For transplantation, the patient was positioned so that the cartilage defect was facing upward, and synovial MSC suspension was placed on the cartilage defect with a syringe under arthroscopic control. The defect with the applied suspension then was held in the upward position for 10 minutes. Five patients underwent concomitant ACL reconstructions, among whom two had meniscus suturing performed simultaneously. For MRI quantification, the cartilage defect was scored from 0 to 5. Second-look arthroscopy was performed for four patients and biopsy specimens were evaluated histologically. Clinical outcome was assessed using the Lysholm score and Tegner Activity Level Scale at final followup. Comparisons of MRI and Lysholm scores before and after treatment for each patient were analyzed using the Wilcoxon signed-rank test.


RESULTS
MRI score (median ± 95% CI) was 1.0 ± 0.3 before and 5.0 ± 0.7 after, and increased after treatment in each patient (p = 0.005). Second-look arthroscopy in four patients showed that the cartilage defect appeared to be qualitatively better in all cases. Histologic analyses showed hyaline cartilage in three patients and fibrous cartilage in one at the deep zone. The Lysholm score (median ± 95% CI) was 76 ± 7 before and 95 ± 3 after, and increased after treatment in each patient (p = 0.005). The Tegner Activity Level Scale did not decrease after treatment in each patient.


CONCLUSIONS
For this small initial case series, transplantation of synovial MSCs was effective in terms of MRI score, qualitative histology, and Lysholm score. The use of synovial MSCs has an advantage in that the cells can be prepared at passage 0 in only 14 days. Transplantation of synovial MSCs may be less invasive than mosaicplasty and autologous chondrocyte implantation. To conclusively show the effectiveness of this treatment requires comparative studies, especially with more established arthroscopic procedures, such as marrow stimulation techniques.


METHODS
Level IV, therapeutic study.
Center for Stem Cell and Regenerative Medicine, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan, sekiya.arm@tmd.ac.jp.
Ichiro
I
Sekiya
Takeshi
T
Muneta
Masafumi
M
Horie
Hideyuki
H
Koga
D000328:Adult; D001182:Arthroscopy; D002358:Cartilage, Articular / Q000293:injuries* / Q000601:surgery*; D005260:Female; D006801:Humans; D007719:Knee Joint; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D013583:Synovial Membrane / Q000166:cytology*; D016896:Treatment Outcome; D055815:Young Adult