Effects of immune cells on mesenchymal stem cells during fracture healing

Figure 4 Schematic overview of the regulatory role of mast cells during fracture healing. Cellular responses during fracture healing are orchestrated by factors secreted/released from mast cells and mesenchymal stem cells (MSCs). Factors derived from mast cells are marked in green. MSC-derived factors are marked in orange. Mast cells communicate with other cells during fracture healing by producing and releasing a large variety of factors e.g., tumor necrosis factor alpha, interleukin 1 beta (IL-1β), IL-6, and IL-8, keratinocytes-derived chemokine (KC or CXCL1), macrophage inflammatory protein 2 (MIP-2 or CXCL2), fibroblast growth factors, vascular endothelial growth factor (VEGF), transforming growth factor beta (TGF-β), receptor activator of nuclear factor kappa-Β ligand, or histamines. MSCs in turn affect mast cells by secreted factors e.g., IL-6, TGF-β, or VEGF. Colored arrows depict stimulation and blunt end lines inhibition. Dashed black arrows indicate differentiation processes. TNF-α: Tumor necrosis factor alpha; IL: Interleukin; FGF: Fibroblast growth factor; TGF-β: Transforming growth factor beta; VEGF: Vascular endothelial growth factor; RANKL: Receptor activator of nuclear factor kappa-Β ligand.