Fernandes Tiago Lazzaretti, Santanna João Paulo Cortez, de Faria Rafaella Rogatto, Pastore Enzo Radaic, Bueno Daniela Franco, Hernandez Arnaldo José
Sports Medicine Division, Institute of Orthopedics and Traumatology, Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo 05403-010, SP, Brazil.
Hospital Sírio-Libanês, São Paulo 05403-010, SP, Brazil.
Pharmaceutics. 2024 Dec 5;16(12):1558. doi: 10.3390/pharmaceutics16121558.
BACKGROUND/OBJECTIVES: Cartilage injuries and osteoarthritis are prevalent public health problems, due to their disabling nature and economic impact. Mesenchymal stromal cells (MSCs) isolated from different tissues have the immunomodulatory capacity to regulate local joint environment. This translational study aims to compare cartilage restoration from MSCs from the synovial membrane (SM) and dental pulp (DP) by a tissue-engineered construct with Good Manufacturing Practices.
A controlled experimental study was conducted on fourteen miniature pigs, using scaffold-free Tissue Engineering Constructs (TECs) from DP and SM MSCs, with a 6-month follow-up. Total thickness cartilage defects were created in both hind knees; one side was left untreated and the other received a TEC from either DP (n = 7) or SM (n = 7). An MRI assessed the morphology using the MOCART scoring system, T2 mapping evaluated water, and collagen fiber composition, and histological analysis was performed using the ICRS-2 score.
The untreated group had a mean MOCART value of 46.2 ± 13.4, while the SM-treated group was 65.7 ± 15.5 ( < 0.05) and the DP-treated group was 59.0 ± 7.9 (n.s.). The T2 mapping indicated a mean value of T2 of 54.9 ± 1.9 for native cartilage, with the untreated group at 50.9 ± 2.4 ( < 0.05). No difference was found between the T2 value of native cartilage and the treated groups. The ICRS-2 mean values were 42.1 ± 14.8 for the untreated group, 64.3 ± 19.0 for SM ( < 0.05), and 54.3 ± 12.2 for DP (n.s.).
MRI and histological analysis indicated that TEC treatment led to superior cartilage coverage and quality compared to the defect group. TECs from SM demonstrated better results than the defect group in the histological assessment.
背景/目的：软骨损伤和骨关节炎是普遍存在的公共卫生问题，因其具有致残性及经济影响。从不同组织分离出的间充质基质细胞（MSC）具有免疫调节能力，可调节局部关节环境。本转化研究旨在通过符合药品生产质量管理规范的组织工程构建体，比较滑膜（SM）和牙髓（DP）来源的MSC对软骨的修复情况。
对14只小型猪进行对照实验研究，使用来自DP和SM MSC的无支架组织工程构建体（TEC），随访6个月。在双侧后膝关节制造全层软骨缺损；一侧不治疗，另一侧接受来自DP（n = 7）或SM（n = 7）的TEC。通过MRI使用MOCART评分系统评估形态，T2成像评估水和胶原纤维组成，并使用ICRS-2评分进行组织学分析。
未治疗组的平均MOCART值为46.2±13.4，而SM治疗组为65.7±15.5（P<0.05），DP治疗组为59.0±7.9（无统计学差异）。T2成像显示天然软骨的T2平均值为54.9±1.9，未治疗组为50.9±2.4（P<0.05）。天然软骨与治疗组之间的T2值未发现差异。未治疗组的ICRS-2平均值为42.1±14.8，SM组为64.3±19.0（P<0.05），DP组为54.3±12.2（无统计学差异）。
MRI和组织学分析表明，与缺损组相比，TEC治疗可实现更好的软骨覆盖和质量。在组织学评估中，SM来源的TEC显示出比缺损组更好的结果。
