Regeneration of Tendon in the Rat Rotator Cuff Defect Model With Adipose-Derived Stem Cells

Rotator cuff tear is a common shoulder injury that can cause pain and limited mobility. Recently, there has been growing interest in regeneration therapy, including platelet rich plasma, growth factor, and stem cells. Adipose-derived stem cells (ADSCs) have been shown to have the potential to differentiate into various types of cells, including tendon cells. However, although few studies using ADSCs have been reported for tendon healing, but there are few studies about efficacy for rotator cuff regeneration in animal or patients. Moreover, there was no study focus on concentration of ADSCs in terms of tendon healing. Hence, the purpose of this study was to investigate the efficacy of ADSCs on the regeneration of rotator cuff tendon defect in a rat model. Three different concentrations of ADSCs (1×10 5 , 5×10 5 , 1×10 6 cell/100uL) were obtained and used. Fifty adult male Sprague-Dawley rats were divided into to five groups, each with ten (intact tendon, defect only, low / middle / high concertation ADSCs injection). After making tendon defect (2mm × 4mm), 100µL of three different ADSCs were injected. All animals were sacrificed four weeks after injection. Macroscopic analysis using modified semi-quantitative system of Stoll, histological measurement by Movin score and collagen fiber organization, and biomechanical test measuring tensile strength were done and compared in the five groups. Macroscopic evaluation showed ADSCs groups had improvement of tendon appearance compared to control groups. The average total macroscopic score was significantly lower in the high concentration ADSC group (3.0) than middle (4.8) and low (7.2) group. Histologically, middle and high concentration ADSCs groups showed cellularity and vascularity close to normal tendon compared to low concentration ADGCs and defect group. Organization and stainability of collagen fiber in high concentration ADGCs was statistically different from the defect group. The ultimate failure load was significantly higher in the high concentration ADSCs group, 30.6 N than those in the defect group, 17.4 N. The application of ADSCs in a rat rotator cuff defect model improved the tendon healing. The concentration of ADSCs affected biomechanical property of healed tendon. We found that higher concentrations of ADSCs led to improved tendon regeneration and a higher level of collagen production. Further research is needed to investigate the optimal concentration for tendon regeneration