Effects of immune cells on mesenchymal stem cells during fracture healing

Figure 2 Schematic overview of the regulatory role of neutrophils during fracture healing. Factors secreted/released from neutrophils and mesenchymal stem cells (MSCs) regulate cellular responses during fracture healing. Neutrophil-derived factors are marked in green. MSC-derived factors are marked in orange. Local increase in danger associated molecular patterns, interleukins 8 (IL-8 or CXCL8) and 1 alpha (IL-1α) attract neutrophils to the fracture site. There neutrophils secrete /release factors e.g. tumor necrosis factor alpha, IL-10, C-C-motif chemokine ligand 2, azurocidin 1, cathelicidin (LL-37), vascular endothelial growth factor, angiopoietin 1, matrix metalloproteinase 9, reactive oxygen species, neutrophil extracellular traps, and extracellular matrix components to interact with other cells at the site of fracture. MSCs secrete/release factors e.g., granulocyte-macrophage colony-stimulating factor, IL-6 and 8 to affect neutrophils. Colored arrows depict stimulation and blunt end lines inhibition. Dashed black arrows indicate differentiation processes. DAMPs: Danger associated molecular patterns; IL: Interleukin; TNF-α: Tumor necrosis factor alpha; CCL2: C-C-motif chemokine ligand 2; CXCL: C-X-C motif chemokine ligand; Azu1: Azurocidin 1; VEGF: Vascular endothelial growth factor; Ang1: Angiopoietin 1; MMP9: Matrix metalloproteinase 9; ROS: Reactive oxygen species; NETs: Neutrophil extracellular traps; ECM: Extracellular matrix; GM-CSF: Granulocyte-macrophage colony-stimulating factor.