Gao Qi, Rhee Claire, Maruyama Masahiro, Li Zhong, Shen Huaishuang, Zhang Ning, Utsunomiya Takeshi, Huang Elijah Ejun, Yao Zhenyu, Bunnell Bruce A, Lin Hang, Tuan Rocky S, Goodman Stuart B
Orthopaedic Research Laboratories, Department of Orthopaedic Surgery, Stanford University School of Medicine, Stanford, CA 94304, USA.
Center for Cellular and Molecular Engineering, Department of Orthopaedic Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA 15219, USA.
Biomedicines. 2021 May 1;9(5):499. doi: 10.3390/biomedicines9050499.
Wear debris generated from the bearing surfaces of joint arthroplasties leads to acute and chronic inflammation, which is strongly associated with implant failure. Macrophages derived from monocytes recruited to the local tissues have a significant impact on bone healing and regeneration. Macrophages can adopt various functional phenotypes. While M1 macrophages are pro-inflammatory, M2 macrophages express factors important for tissue repair. Here, we established a 3D co-culture system to investigate how the immune system influences the osteogenic differentiation of mesenchymal stem cells (MSCs) in the presence of micron-sized particles. This system allowed for the simulation of an inflammatory reaction via the addition of Lipopolysaccharide-contaminated polyethylene particles (cPE) and the characterization of bone formation using micro-CT and gene and protein expression. Co-cultures of MSCs with M2 macrophages in the presence of cPE in a 3D environment resulted in the increased expression of osteogenic markers, suggesting facilitation of bone formation. In this model, the upregulation of M2 macrophage expression of immune-associated genes and cytokines contributes to enhanced bone formation by MSCs. This study elucidates how the immune system modulates bone healing in response to an inflammatory stimulus using a unique 3D culture system.
关节置换术的轴承表面产生的磨损碎屑会导致急性和慢性炎症，这与植入物失败密切相关。招募到局部组织的单核细胞衍生的巨噬细胞对骨愈合和再生有重大影响。巨噬细胞可以呈现多种功能表型。M1巨噬细胞具有促炎作用，而M2巨噬细胞表达对组织修复重要的因子。在此，我们建立了一个三维共培养系统，以研究在存在微米级颗粒的情况下免疫系统如何影响间充质干细胞（MSC）的成骨分化。该系统通过添加被脂多糖污染的聚乙烯颗粒（cPE）来模拟炎症反应，并使用微型计算机断层扫描以及基因和蛋白质表达来表征骨形成。在三维环境中，在cPE存在的情况下，MSC与M2巨噬细胞共培养导致成骨标志物表达增加，表明促进了骨形成。在该模型中，M2巨噬细胞免疫相关基因和细胞因子表达的上调有助于MSC增强骨形成。本研究阐明了免疫系统如何使用独特的三维培养系统响应炎症刺激来调节骨愈合。
