Matrix-induced autologous chondrocyte implantation in sheep: objective assessments including confocal arthroscopy.
ABSTRACT The assessment of cartilage repair has largely been limited to macroscopic observation, magnetic resonance imaging (MRI), or destructive biopsy. The aims of this study were to establish an ovine model of articular cartilage injury repair and to examine the efficacy of nondestructive techniques for assessing cartilage regeneration by matrix-induced autologous chondrocyte implantation (MACI). The development of nondestructive assessment techniques facilitates the monitoring of repair treatments in both experimental animal models and human clinical subjects. Defects (Ø 6 mm) were created on the trochlea and medial femoral condyle of 21 sheep randomized into untreated controls or one of two treatment arms: MACI or collagen-only membrane. Each group was divided into 8-, 10-, and 12-week time points. Repair outcomes were examined using laser scanning confocal arthroscopy (LSCA), MRI, histology, macroscopic ICRS grading, and biomechanical compression analysis. Interobserver analysis of the randomized blinded scoring of LSCA images validated our scoring protocol. Pearson correlation analysis demonstrated the correlation between LSCA, MRI, and ICRS grading. Testing of overall treatment effect independent of time point revealed significant differences between MACI and control groups for all sites and assessment modalities (Asym Sig < 0.05), except condyle histology. Biomechanical analysis suggests that while MACI tissue may resemble native tissue histologically in the early stages of remodeling, the biomechanical properties remain inferior at least in the short term. This study demonstrates the potential of a multisite sheep model of articular cartilage defect repair and its assessment via nondestructive methods.
Article: Cell carriers as the next generation of cell therapy for cartilage repair: a review of the matrix-induced autologous chondrocyte implantation procedure.[show abstract] [hide abstract]
ABSTRACT: Since the first patient was implanted with autologous cultured chondrocytes more than 20 years ago, new variations of cell therapies for cartilage repair have appeared. Autologous chondrocyte implantation, a first-generation cell therapy, uses suspended autologous cultured chondrocytes in combination with a periosteal patch. Collagen-covered autologous cultured chondrocyte implantation, a second-generation cell therapy, uses suspended cultured chondrocytes with a collagen type I/III membrane. Today's demand for transarthroscopic procedures has resulted in the development of third-generation cell therapies that deliver autologous cultured chondrocytes using cell carriers or cell-seeded scaffolds. To review the current evidence of the matrix-induced autologous chondrocyte implantation procedure, the most widely used carrier system to date. Also discussed are the characteristics of type I/III collagen membranes, behavior of cells associated with the membrane, surgical technique, rehabilitation, clinical outcomes, and quality of repair tissue. Systematic review. Relevant publications were identified by searching Medline from its inception (1949) to December 2007; peer-reviewed publications of preclinical and clinical cell behavior, manufacturing process, surgical technique, and rehabilitation protocols were identified. Preclinical and clinical studies were included if they contained primary data and used a type I/III collagen membrane. Data from these studies demonstrate that patients treated with matrix-induced autologous chondrocyte implantation have an overall improvement in clinical outcomes. Reduced visual analog scale pain levels (range, 1.7-5.32 points) and improvements in the modified Cincinnati (range, 3.8-34.2 points), Lysholm-Gillquist (range, 23.09-47.6 points), Tegner-Lysholm (range, 1.39-3.9 points), and International Knee Documentation Classification scale (P <.05) were observed. Patients had good-quality (hyaline-like) repair tissue as assessed by arthroscopic evaluation (including International Cartilage Repair Society score), magnetic resonance imaging, and histology, as well as a low incidence of postoperative complications. The findings suggest that matrix-induced autologous chondrocyte implantation is a promising third-generation cell therapy for the repair of symptomatic, full-thickness articular cartilage defects.The American journal of sports medicine 12/2009; 38(6):1259-71. · 3.61 Impact Factor