The Effects of Macrophage Phenotype on Osteogenic Differentiation of MSCs in the Presence of Polyethylene Particles
Qi Gao,
Claire Rhee,
Masahiro Maruyama,
Zhong Li,
Huaishuang Shen,
Ning Zhang,
Takeshi Utsunomiya,
Elijah Ejun Huang,
Zhenyu Yao,
Bruce A. Bunnell,
Hang Lin,
Rocky S. Tuan,
Stuart B. Goodman
Affiliations
Qi Gao
Orthopaedic Research Laboratories, Department of Orthopaedic Surgery, Stanford University School of Medicine, Stanford, CA 94304, USA
Claire Rhee
Orthopaedic Research Laboratories, Department of Orthopaedic Surgery, Stanford University School of Medicine, Stanford, CA 94304, USA
Masahiro Maruyama
Orthopaedic Research Laboratories, Department of Orthopaedic Surgery, Stanford University School of Medicine, Stanford, CA 94304, USA
Zhong Li
Center for Cellular and Molecular Engineering, Department of Orthopaedic Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA 15219, USA
Huaishuang Shen
Orthopaedic Research Laboratories, Department of Orthopaedic Surgery, Stanford University School of Medicine, Stanford, CA 94304, USA
Ning Zhang
Orthopaedic Research Laboratories, Department of Orthopaedic Surgery, Stanford University School of Medicine, Stanford, CA 94304, USA
Takeshi Utsunomiya
Orthopaedic Research Laboratories, Department of Orthopaedic Surgery, Stanford University School of Medicine, Stanford, CA 94304, USA
Elijah Ejun Huang
Orthopaedic Research Laboratories, Department of Orthopaedic Surgery, Stanford University School of Medicine, Stanford, CA 94304, USA
Zhenyu Yao
Orthopaedic Research Laboratories, Department of Orthopaedic Surgery, Stanford University School of Medicine, Stanford, CA 94304, USA
Bruce A. Bunnell
Department of Microbiology, Immunology and Genetics, University of North Texas Health Science Center, Fort Worth, TX 76107, USA
Hang Lin
Center for Cellular and Molecular Engineering, Department of Orthopaedic Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA 15219, USA
Rocky S. Tuan
Center for Cellular and Molecular Engineering, Department of Orthopaedic Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA 15219, USA
Stuart B. Goodman
Orthopaedic Research Laboratories, Department of Orthopaedic Surgery, Stanford University School of Medicine, Stanford, CA 94304, USA
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.
