Engineered Cell Sheets for the Effective Delivery of Adipose-Derived Stem Cells for Tendon-to-Bone Healing

Background: Efforts are being made to treat rotator cuff tears (RCTs) that exhibit poor healing and high retear rates. Tendon-to-bone healing using mesenchymal stem cells is being explored, but research is needed to establish effective delivery options. Purpose: To evaluate the effects of an adipose-derived stem cell (ADSC) sheet on mesenchymal stem cell delivery for tendon-to-bone healing of a chronic RCT in rats and to demonstrate that ADSC sheets enhance tendon-to-bone healing. Study Design: Controlled laboratory study. Methods: Mesenchymal stem cells were obtained from rat adipose tissue, and a cell sheet was prepared using a temperature-responsive dish. To evaluate the efficacy of stem cells produced in a sheet for the lesion, the experiment was conducted with 3 groups: repair group, cell sheet transplantation after repair group, and cell sheet–only group. Histological, biomechanical, and micro–computed tomography (micro-CT) results were compared among the groups. Results: Hematoxylin and eosin staining for histomorphological analysis revealed that the cell sheet transplantation after repair group (5.75 ± 0.95) showed statistically significant higher scores than the repair (2.75 ± 0.50) and cell sheet–only (3.25 ± 0.50) groups ( P < .001). On safranin O staining, the cell sheet transplantation after repair group (0.51 ± 0.04 mm 2 ) had a larger fibrocartilage area than the repair (0.31 ± 0.06 mm 2 ) and cell sheet–only (0.32 ± 0.03 mm 2 ) groups ( P = .001). On micro-CT, bone volume/total volume values were significantly higher in the cell sheet transplantation after repair group (23.98% ± 1.75%) than in the other groups ( P < .039); there was no significant difference in the other values. On the biomechanical test, the cell sheet transplantation after repair group (4 weeks after repair) showed significantly higher results than the other groups ( P < .005). Conclusion: Our study shows that engineered stem cells are a clinically feasible stem cell delivery tool for rotator cuff repair. Clinical Relevance: This laboratory study provides evidence that ADSCs are effective in repairing RCTs, which are common sports injuries.