Introduction: Cell-cell interaction is believed to play an important role in cell-based therapy for bone regeneration. However, the mechanisms involved in the interaction between donor cells and host cells during the bone healing process are still largely unknown. This study investigated the potential effect of vascular endothelial growth factor (VEGF) produced by osteogenically differentiated mesenchymal stromal cells (OMSCs) on the recruitment and regulation of un-differentiated MSCs and macrophages during osteogenesis.
Methods: Factors secreted from MSCs during osteogenic differentiation were monitored by cytokine arrays. Indirect co-culture models were applied to study the effect of VEGF derived from OMSCs on cell motility, cell morphology, and the local immune response. A mouse skull defect model was used to unveil the cell recruitment, macrophage activity and new bone formation following the implantation of OMSCs.
Results: It was found that VEGF secretion increased dramatically when MSCs were subjected to osteogenic differentiation. The secreted VEGF by OMSCs stimulated the recruitment of host MSCs and macrophages to the bone defects. It was noted that OMSCs could regulate the local inflammation by modulating the expression of pro-inflammatory cytokines in macrophages. Furthermore, neutralization of OMSC-secreted VEGF led to a significant decrease of cell recruitment, cytokine secretion and new bone formation.
Conclusions: This study demonstrated that VEGF secreted by OMSCs plays a pivotal role in the cell recruitment and regulation of local immune response during osteogenesis.