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      Arthroscopic Transplantation of Synovial Stem Cells Improves Clinical Outcomes in Knees With Cartilage Defects

      research-article
      , MD, PhD , , MD, PhD, , MD, PhD, , MD, PhD
      Clinical Orthopaedics and Related Research
      Springer US

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          Abstract

          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.

          Questions/purposes

          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.

          Level of Evidence

          Level IV, therapeutic study.

          Related collections

          Most cited references26

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          Human autologous culture expanded bone marrow mesenchymal cell transplantation for repair of cartilage defects in osteoarthritic knees.

          There is no widely accepted method to repair articular cartilage defects. Bone marrow mesenchymal cells have the potential to differentiate into bone, cartilage, fat and muscle. Bone marrow mesenchymal cell transplantation is easy to use clinically because cells can be easily obtained and can be multiplied without losing their capacity of differentiation. The objective of this study was to apply these cell transplantations to repair human articular cartilage defects in osteoarthritic knee joints. Twenty-four knees of 24 patients with knee osteoarthritis (OA) who underwent a high tibial osteotomy comprised the study group. Adherent cells in bone marrow aspirates were culture expanded, embedded in collagen gel, transplanted into the articular cartilage defect in the medial femoral condyle and covered with autologous periosteum at the time of 12 high tibial osteotomies. The other 12 subjects served as cell-free controls. In the cell-transplanted group, as early as 6.3 weeks after transplantation the defects were covered with white to pink soft tissue, in which metachromasia was partially observed. Forty-two weeks after transplantation, the defects were covered with white soft tissue, in which metachromasia was observed in almost all areas of the sampled tissue and hyaline cartilage-like tissue was partially observed. Although the clinical improvement was not significantly different, the arthroscopic and histological grading score was better in the cell-transplanted group than in the cell-free control group. This procedure highlights the availability of autologous culture expanded bone marrow mesenchymal cell transplantation for the repair of articular cartilage defects in humans. Copyright 2002 OsteoArthritis Research Society International.
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            Autologous bone marrow-derived mesenchymal stem cells versus autologous chondrocyte implantation: an observational cohort study.

            First-generation autologous chondrocyte implantation has limitations, and introducing new effective cell sources can improve cartilage repair. This study was conducted to compare the clinical outcomes of patients treated with first-generation autologous chondrocyte implantation to patients treated with autologous bone marrow-derived mesenchymal stem cells (BMSCs). Cohort study; Level of evidence, 3. Seventy-two matched (lesion site and age) patients underwent cartilage repair using chondrocytes (n = 36) or BMSCs (n = 36). Clinical outcomes were measured before operation and 3, 6, 9, 12, 18, and 24 months after operation using the International Cartilage Repair Society (ICRS) Cartilage Injury Evaluation Package, which included questions from the Short-Form Health Survey, International Knee Documentation Committee (IKDC) subjective knee evaluation form, Lysholm knee scale, and Tegner activity level scale. There was significant improvement in the patients' quality of life (physical and mental components of the Short Form-36 questionnaire included in the ICRS package) after cartilage repair in both groups (autologous chondrocyte implantation and BMSCs). However, there was no difference between the BMSC and the autologous chondrocyte implantation group in terms of clinical outcomes except for Physical Role Functioning, with a greater improvement over time in the BMSC group (P = .044 for interaction effect). The IKDC subjective knee evaluation (P = .861), Lysholm (P = .627), and Tegner (P = .200) scores did not show any significant difference between groups over time. However, in general, men showed significantly better improvements than women. Patients younger than 45 years of age scored significantly better than patients older than 45 years in the autologous chondrocyte implantation group, but age did not make a difference in outcomes in the BMSC group. Using BMSCs in cartilage repair is as effective as chondrocytes for articular cartilage repair. In addition, it required 1 less knee surgery, reduced costs, and minimized donor-site morbidity.
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              • Article: not found

              Evaluation of knee ligament surgery results with special emphasis on use of a scoring scale.

              We have designed a scoring scale for knee ligament surgery follow-up emphasizing evaluation of symptoms of instability. Instability is defined as "giving way" during activity. Our scoring scale was compared to a slightly modified Larson scale in patients with anteromedial and/or anterolateral instability, posterolateral and straight posterior instability, chondromalacia patellae, and meniscus lesion. The two scales gave basically the same results in patients with meniscus rupture. In patients with unstable knees, the new scale gave a significantly lower total score. Thus, the new scale evaluates functional impairment due to clinical instability better than the modified Larson scale. The total score, with the new scoring scale, corresponded to the patients' own opinion of function and to the presence or absence of signs of instability.
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                Author and article information

                Contributors
                sekiya.arm@tmd.ac.jp
                Journal
                Clin Orthop Relat Res
                Clin. Orthop. Relat. Res
                Clinical Orthopaedics and Related Research
                Springer US (New York )
                0009-921X
                1528-1132
                30 April 2015
                30 April 2015
                July 2015
                : 473
                : 7
                : 2316-2326
                Affiliations
                [ ]Center for Stem Cell and Regenerative Medicine, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519 Japan
                [ ]Department of Joint Surgery and Sports Medicine, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan
                Article
                4324
                10.1007/s11999-015-4324-8
                4457765
                25925939
                8b1c8355-1314-448f-aa44-3b810c53dc1c
                © The Author(s) 2015

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

                History
                : 17 August 2014
                : 17 April 2015
                Categories
                Clinical Research
                Custom metadata
                © The Association of Bone and Joint Surgeons® 2015

                Orthopedics
                Orthopedics

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