Tissue Engineering Construct for Articular Cartilage Restoration with Stromal Cells from Synovium vs Dental Pulp - A Pre-Clinical Study

Introduction: Cartilage injuries and osteoarthritis are very prevalent and considered a public health problem, as they are highly disabling and represent an economic burden. Mesenchymal Stromal Cells (MSCs) can be isolated from different tissues and have the immunomodulatory capacity to regulate local articular joint environment. This translational study aims to compare the cartilage restoration from MSCs from the synovial membrane (SM) and dental pulp (DP), by tissue engineered treatment in a Good Manufacturing Practices. Materials and Methods: A controlled experimental study in fourteen miniature pigs was performed, using scaffold-free Tissue Engineering Construct (TEC) from DP and SM MSCs, with 6 months follow-up. Total thickness cartilage defects were performed in both posterior knees. The defect was left empty on one side, and the other received TEC from DP (n=7) or from SM (n=7). MRI assessed morphology with the MOCART scoring system. T2 mapping assessed water and collagen fiber composition. Histology evaluated cartilage repair using the ICRS-2 score. Results: The mean MOCART value in the untreated group was 46.2 ± 13.4, while the group treated with TEC from SM was 65.7 ± 15.5 (p<0.05) and from DP was 59.0 ± 7.9 (n.s.). The T2 mapping showed a mean value of T2 of 54.9 ± 1.9 in the native cartilage and the untreated group exhibited a mean T2 value of 50.9 ± 2.4 (p<0.05). No difference was found between the native cartilage (54.9 ± 1.9) and the treated groups from DP (54.54 ± 1.47) and SM (54.31 ± 2.07). The ICRS-2 mean value was 42.1 ± 14.8 in the untreated group, 64.3 ± 19.0 in the group with TEC from SM (p<0,05) and 54.3 ± 12.2 (n.s.) from DP. Conclusion: MRI and histological analysis indicated that TEC treatment led to superior cartilage coverage and quality compared to the control group. TEC from SM demonstrated better results than the defect group in the histological assessment and had no difference to the treatment with TEC from the DP. In the MRI assessment, both DP and SM groups showed better results in comparison to the defect group.