The phenotypic change of macrophages (M s) play a crucial role in the musculoskeletal homeostasis and repair process. Although mesenchymal stem cells (MSCs) have been shown as a novel approach in tissue regeneration, the therapeutic potential of MSCs mediated by the interaction between MSC-derived paracrine mediators and M s remains elusive. This review focused on the elucidation of paracrine crosstalk between MSCs and M s during musculoskeletal diseases and injury. The search method was based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and Cochrane Guidelines. The search strategies included “MeSH” terms and other related terms of MSC-derived mediators and M s. Ten studies formed the basis of this review. The current finding suggested that MSCs administration promoted proliferation and activation of CD163 or CD206 M2 M s in parallel with reduction of pro-inflammatory cytokines and increase of anti-inflammatory cytokines. During such period, M s also induced MSCs into a motile and active phenotype via the influence of pro-inflammatory cytokines. Such crosstalk between M s and MSCs further strengthen the effect of paracrine mediators from MSCs to regulate M s phenotypic alteration. In conclusion, MSCs in musculoskeletal system, mediated by the interaction between MSC paracrine and M s, has therapeutic potential in musculoskeletal diseases.
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