The shift in macrophages polarization after tendon injury: A systematic review

Abstract Background The role of macrophages (Mφs) in tendon injury healing is controversy. The aims of this study were to determine whether there is a shift in Mφs polarization after an acute and chronic tendon injury ​and to assess whether the Mφs polarization between the partial and complete rupture is different. Methods This systematic review of the scientific literature was based on the PRISMA and Cochrane guidelines. PubMed database and EMBASE database were used for specific search criteria. Only studies measuring Mφs using specific cell markers in Achilles tendon tissue and rotator cuff tendon tissue were included, respectively. Results Five Achilles tendon injury studies and four rotator cuff injury studies were included. Expression of the pan Mφs marker CD68 was significantly upregulated in acute Achilles tendon ruptures compared to intact tendons, while no significant changes were found in Mφs polarization markers CD80 (M1 Mφs) and CD206 (M2 Mφs). High levels of CD86 (M1 Mφs) and CD206 were observed in acute partial rupture. Expression of CD68 and CD206 were significantly upregulated in chronic rotator cuff tendinopathy and downregulated as structural failure increases. A low level of CD206 was observed in complete tendon rupture regardless of acute or chronic injury. Discussion and conclusion In spite of the limited number of articles included, findings from this study suggested that the process of inflammation plays an important role in acute Achilles tendon injuries, indicated by the increased expression of CD68+ Mφs. Low levels of CD206+ Mφs were constantly observed in complete Achilles tendon rupture, while high levels of CD80+ Mφs and CD206+ Mφs were observed in partial Achilles tendon rupture, which suggested the potential correlation between M2 Mφs and tendon structure. For chronic rotator cuff injury, CD68+ Mφs and CD206+ Mφs were higher in tendinopathic tissues in comparison to the intact control tissues. Both CD68+ Mφs and CD206+ Mφs has an inverse relation to the structural failure in the torn rotator cuff tendon. After tendon rupture, the time point of biopsy specimen collection is an important factor, which could occur in the acute phase or chronic phase. Collectively, the understanding of the roles in Mφs after tendon injury is inadequate, and more research efforts should be devoted to this direction.