Five-Year Outcomes After Implantation of a Scaffold-Free Tissue-Engineered Construct Generated From Autologous Synovial Mesenchymal Stromal Cells for Repair of Knee Chondral Lesions

Abstract

Background: In an earlier study, a scaffold-free tissue-engineered construct (TEC) derived from autologous synovial membrane mesenchymal stromal cells (MSCs) was developed and demonstrated to be safe and effective for cartilage repair at 2 years postoperatively. Purpose: To investigate clinical outcomes and magnetic resonance imaging (MRI) findings at 5 years after implantation. Study Design: Case series; Level of evidence, 4. Methods: This was an observational first-in-human study limited to 5 patients (age, 28-46 years) with symptomatic knee chondral lesions (size, 1.5-3.0 cm2) on the medial femoral condyle, lateral femoral condyle, or femoral groove. Synovial MSCs were isolated from arthroscopic biopsy specimens and cultured to develop a TEC that matched the lesion size. The TECs were then implanted into chondral defects without fixation and assessed at up to 5 years postoperatively. The patients were clinically evaluated using the visual analog scale for pain, Lysholm score, Tegner score, and Knee injury and Osteoarthritis Outcome Score. An MRI scan evaluation was also performed for morphologic and compositional quality of the repair tissue at both 2 and 5 years of follow-up. Results: All clinical scores were significantly improved from the preoperative evaluation to the 2- and 5-year follow-ups and the results were stable over time. The MRI scan evaluation showed cartilage defects filled with newly generated tissues with good tissue integration to adjacent host cartilage over time. The cartilage thickness and surface smoothness of the repair cartilage were maintained up to 5 years postoperatively. The MOCART (magnetic resonance observation of cartilage repair tissue) 2.0 Knee Scores remained high at 5 years, although the total points decreased slightly. Conclusion: The results highlight the efficacy and feasibility of autologous scaffold-free TEC derived from synovial MSCs for regenerative cartilage repair via a sutureless and simple implantation procedure, showing good clinical outcomes and MRI findings with stable results at midterm follow-up. Further follow-up will be needed to assess the long-term quality of the repair tissue.

Development of scaffold-free tissue-engineered constructs derived from mesenchymal stem cells with serum-free media for cartilage repair and long-term preservation

“…A previous study developed a scaffold-free three-dimensional tissue-engineered construct (TEC) comprised of sMSCs and the self-synthesized extracellular matrix (ECM) [9]. Clinical studies have veri ed that the autograft implantation of TEC in ve patients did not have serious adverse events and improved the clinical scores up to 5 years postoperatively, suggesting the amelioration of knee cartilage defects (Registration: 000008266; UMIN Clinical Trials Registry number) [10,11]. However, even with this promising candidate, by elucidating the early clinical proof of concept (POC), clinical applications remain a challenging task, requiring the use of a growth medium containing fetal bovine serum (FBS), which has potential risks concerning contamination by viruses and other pathogens or susceptibility to a high lot-tolot variability [12].…”

Structural and Molecular Changes of Human Chondrocytes Exposed to the Rotating Wall Vessel Bioreactor

“…Tissue engineering of cartilage and restoration of cartilage defects are currently hot topics in translational regenerative medicine. Known techniques are cell-based approaches, such as autologous chondrocyte implantation [5,6], matrix-induced autologous chondrocyte implantation [7], or tissue-engineered cartilage implantation [8,9]. Several bio-printing approaches and bioreactors for tissue engineering of cartilage are currently available and reviewed in [10].…”