Monocyte Chemoattractant Protein-1 from a Conditioned Medium of Bone Marrow-Derived Mesenchymal Stem Cells Promotes Bone Regeneration by Enhancing Macrophage Phenotype Switching

Background We have reported that the cytokines and chemokines contained in conditioned media of human mesenchymal stem cells (MSC-CM), which were derived from bone marrow, promote bone regeneration. We recently reported macrophage phenotype switching towards the anti-inflammatory M2 phenotype induced by MSC-CM and its potential to establish regenerative condition and assist subsequent bone regeneration. However, the specific factors in the MSC-CM responsible for this process remain unclear. Monocyte chemoattractant protein (MCP) -1, present in MSC-CM, promotes cell migration and activation of the monocyte-macrophage lineage; therefore, we hypothesized that MCP-1 is one of the key factors in MSC-CM-induced macrophage phenotype switching. The effect of MCP-1 on MSC-CM-induced macrophage phenotype switching and subsequent bone regeneration was investigeted in this study. Methods MCP-1 was depleted from MSC-CM (depMSC-CM) and used in subsequent experiments. Rat bone marrow macrophages were incubated in MSC-CM or depMSC-CM and expression of macrophage markers was examined in vitro . In addition, the effect of MSC-CM and depMSC-CM on bone regeneration and macrophage phenotype switching were evaluated using rat calvaria defect model in vivo . Results MSC-CM enhanced M2 macrophage marker expression in rat bone marrow macrophages compared to those treated with depMSC-CM in vitro . In addition, MSC-CM increased the number of M2 macrophage marker-positive cells in bone defects and enhanced subsequent bone regeneration in a rat calvaria bone defect model. Conclusions MCP-1 seemed to play an essential role in MSC-CM-induced macrophage phenotypic switching and subsequent bone regeneration.