The Effect of Purified Human Bone Marrow-Derived Mesenchymal Stem Cells on Rotator Cuff Tendon Healing in an Athymic Rat.

Abstract

To evaluate the ability of purified human bone marrow-derived mesenchymal stem cells (MSCs) to augment healing of an acute small- to medium-sized rotator cuff repair in a small-animal model, evaluating the structure and composition of the healing tendon-bone interface with histologic and biomechanical analyses. Fifty-two athymic rats underwent unilateral detachment and transosseous repair of the supraspinatus tendon augmented with either fibrin glue (control group) or fibrin glue with 10⁶ human MSCs (experimental group) applied at the repair site. Flow cytometry verified the stem cell phenotype of the cells as CD73⁺, CD90⁺, CD105⁺, CD14^-, CD34^-, and CD45^-. Rats were killed at 2 and 4 weeks, with 10 from each group used for biomechanical testing and 3 for histologic analysis. Safranin O staining identified increased fibrocartilage formation at the repair site at 2 weeks in the human MSC group (18.6% ± 2.9% vs 9.1% ± 1.6%, P = .026). Picrosirius staining identified decreased energy (36.88 ± 4.99 J vs 54.97 ± 8.33 J, P = .04) and increased coherence in the human MSC group (26.96% ± 15.32% vs 14.53% ± 4.10%, P = .05), indicating improved collagen orientation. Biomechanical testing showed a significant increase in failure load (11.5 ± 2.4 N vs 8.5 ± 2.4 N, P = .002) and stiffness (7.1 ± 1.2 N/mm vs 5.7 ± 2.1 N/mm, P < .001) in the experimental group compared with the control group at 2 weeks. These effects dissipated by 4 weeks, with no significant differences in fibrocartilage formation (35% ± 5.0% vs 26.6% ± 0.6%, P = .172) or biomechanical load to failure (24.6 ± 7.1 N vs 21.5 ± 4.1 N, P = .361) or stiffness (13.5 ± 3.1 N/mm vs 16.1 ± 5.6 N/mm, P = .384). All failures occurred at the bone-tendon interface. Rotator cuff repair augmentation with purified human MSCs improved early histologic appearance and biomechanical strength of the repair at 2 weeks, although the effects dissipated by 4 weeks with no significant differences between groups. Human MSCs may improve early rotator cuff healing during the first 2 weeks after repair.