The Laboratory of Orthopaedic Tissue Regeneration & Orthobiologics, Department of Bioengineering, Clemson University, Clemson, SC, USA.
Steadman Hawkins Clinic of the Carolinas, Greenville Health System, Greenville, SC, USA.
J Tissue Eng Regen Med. 2018 Apr;12(4):1097-1110. doi: 10.1002/term.2610. Epub 2017 Nov 29.
Osteoarthritis (OA) is a disease of the synovial joint marked by chronic, low-grade inflammation leading to cartilage destruction. Regenerative medicine strategies for mitigating OA progression and/or promoting cartilage regeneration must be assessed using models that mimic the hallmarks of OA. More specifically, these models should maintain synovial macrophage phenotype in their native micro-environment. Herein, an in vitro coculture model of patient-matched human OA cartilage and synovium was assessed for viability, macrophage phenotype, and progressive cartilage destruction in the presence of an inflammatory milieu. Additionally, the influence of synovial macrophages and their polarization within the model was defined using depletion studies. Finally, the model was used to compare the ability of human amniotic stem cells (hAMSCs) and human adipose stem cells (hADSCs) to mitigate OA progression. OA cocultures demonstrated progressive and significant reductions in chondrocyte viability and cartilage glycosaminoglycan content within a proinflammatory environment. Selective depletion of synovial macrophages resulted in significant decreases in M1:M2 percentage ratio yielding significant reductions in concentrations of interleukin-1 beta, matrix metalloproteinase-13 and attenuation of cartilage damage. Finally, hAMSCs were found to be more chondroprotective versus hADSCs as indicated by significantly improved OA chondrocyte viability (89.8 ± 2.4% vs. 58.4 ± 2.4%) and cartilage glycosaminoglycan content (499.0 ± 101.9 μg/mg dry weight vs. 155.0 ± 26.3 μg/mg dry weight) and were more effective at shifting OA synovial macrophage M1:M2 ratio (1.3:1 vs. 5:1), respectively. Taken together, the coculture model mimics salient features of OA, including macrophage-mediated cartilage destruction that was effectively abrogated by hAMSCs but not hADSCs.
骨关节炎（OA）是一种滑膜关节疾病，其特征为慢性、低水平炎症，导致软骨破坏。减轻 OA 进展和/或促进软骨再生的再生医学策略必须使用模拟 OA 特征的模型进行评估。更具体地说，这些模型应保持滑膜巨噬细胞表型在其天然微环境中。本文评估了患者匹配的人 OA 软骨和滑膜的体外共培养模型在炎症环境中的生存能力、巨噬细胞表型和进行性软骨破坏。此外，使用耗竭研究来定义模型中滑膜巨噬细胞及其极化的影响。最后，该模型用于比较人羊膜干细胞（hAMSCs）和人脂肪干细胞（hADSCs）减轻 OA 进展的能力。OA 共培养物在促炎环境中表现出进行性和显著降低的软骨细胞活力和软骨糖胺聚糖含量。滑膜巨噬细胞的选择性耗竭导致 M1:M2 百分比比值显著降低，导致白细胞介素-1β、基质金属蛋白酶-13 的浓度显著降低，并减轻软骨损伤。最后，发现 hAMSCs 比 hADSCs 更具有软骨保护作用，表现在 OA 软骨细胞活力（89.8 ± 2.4% 比 58.4 ± 2.4%）和软骨糖胺聚糖含量（499.0 ± 101.9 μg/mg 干重比 155.0 ± 26.3 μg/mg 干重）显著改善，并且更有效地改变 OA 滑膜巨噬细胞 M1:M2 比值（1.3:1 比 5:1）。总之，共培养模型模拟了 OA 的显著特征，包括巨噬细胞介导的软骨破坏，hAMSCs 可有效消除这种破坏，而 hADSCs 则不能。
