RESUMEN
The phenotypic change of macrophages (Mφs) plays 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 Mφs remains elusive. This review focused on the elucidation of paracrine crosstalk between MSCs and Mφs during musculoskeletal diseases and injury. The search method was based on the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) and Cochrane Guidelines. The search strategies included MeSH terms and other related terms of MSC-derived mediators and Mφs. Ten studies formed the basis of this review. The current finding suggested that MSC administration promoted proliferation and activation of CD163+ or CD206+ M2 Mφs in parallel with reduction of proinflammatory cytokines and increase in anti-inflammatory cytokines. During such period, Mφs also induced MSCs into a motile and active phenotype via the influence of proinflammatory cytokines. Such crosstalk between Mφs and MSCs further strengthens the effect of paracrine mediators from MSCs to regulate Mφs phenotypic alteration. In conclusion, MSCs in musculoskeletal system, mediated by the interaction between MSC paracrine and Mφs, have therapeutic potential in musculoskeletal diseases.
RESUMEN
In the field of bone research, the importance of the function of skeletal macrophages (sMΦ) and their crucial role in immune homeostasis and bone regeneration has been extensively studied. The aim of the present systematic review was to summarize the role of sMΦ in bone fracture healing and to evaluate their potential for immunoregulatory therapy in bone regeneration. A systematic literature search of PubMed and Embase® was performed to retrieve studies on the role of sMΦ in bone injury repair. The Systematic Review Centre for Laboratory animal Experimentation tool was used to assess the risk of bias of the studies included. A total of four articles were included in the present review. A relatively high risk of bias was identified in the included articles as none of the assessors in these studies were blinded. sMΦ were defined by the surface markers F4/80+, Mac-2- / low, TRAP-, CD169+, Ly6G- and CD115low. All of the studies provided support for the essential role of sMΦ in intramembranous ossification or endochondral ossification during fracture healing. F4/80+Mac-2-CD169+ sMΦ are a promising therapeutic target for immunoregulatory therapy of bone repair due to their essential role in bone formation and homeostasis. Future studies aimed at profiling and modulating sMΦ to promote bone regeneration are required.