Adipose Stem Cell–Derived Exosomes Decrease Fatty Infiltration and Enhance Rotator Cuff Healing in a Rabbit Model of Chronic Tears

Abstract

Background: Fatty infiltration and poor tendon-bone healing in chronic rotator cuff tears (RCTs) are associated with unsatisfactory prognosis. Adipose stem cell–derived exosomes (ASC-Exos), having multiple biological effects, can prevent muscle degeneration in acute RCTs. However, the effects of ASC-Exos on fatty infiltration and tendon-bone healing in chronic RCTs remain unknown. Purpose: To study the effects of ASC-Exos on fatty infiltration and tendon-bone healing in a chronic RCT rabbit model. Study Design: Controlled laboratory study. Methods: At week 0, we randomly allocated 35 rabbits to receive sham surgery (14 rabbits) or establish a bilateral RCT model (21 rabbits, detachment of the supraspinatus tendon). At week 6, a total of 7 rabbits received sham surgery, and 7 rabbits with RCT were sacrificed for fatty infiltration assay. The remaining 14 rabbits with bilateral RCTs were randomly assigned to a saline group (7 rabbits that received local saline injection and rotator cuff repair) or an ASC-Exos group (7 rabbits that received local ASC-Exos injection and rotator cuff repair). At week 18, all rabbits were sacrificed for histological examination and biomechanical testing. Results: At week 18, the ASC-Exos group showed significantly lower fatty infiltration (14.01% ± 2.85%) compared with the saline group (21.79% ± 3.07%) (P < .001), and no statistical difference compared with the time of repair (10.88% ± 2.64%) (P = .127). For tendon-bone healing, the ASC-Exos group showed a higher histological score and more newly regenerated fibrocartilage at the repair site than did the saline group. Regarding biomechanical testing, the ASC-Exos group showed significantly higher ultimate load to failure, stiffness, and stress than the saline group. Conclusion: Local injection of ASC-Exos in chronic RCTs at the time of repair could prevent the progress of fatty infiltration, promote tendon-bone healing, and improve biomechanical properties. Clinical Relevance: ASC-Exos injection may be used as a cell-free adjunctive therapy to inhibit fatty infiltration and improve rotator cuff healing in the repair of chronic RCTs.