Healing Effect of Subcutaneous Administration of Granulocyte Colony-Stimulating Factor on Acute Rotator Cuff Injury in a Rat Model.

Granulocyte colony-stimulating factor (G-CSF) is a cytokine that mobilizes bone marrow-derived cells (BMDCs) to peripheral blood and has been clinically used to treat neutropenia. Previously, we reported that BMDCs migrated into the rotator cuff repair site via peripheral blood in the healing process. However, techniques to accelerate the healing process using the peripheral blood pathway have not been established. We evaluated whether G-CSF has a noteworthy effect on improving rotator cuff healing by enhancing the influx of BMDCs into the peripheral blood. We used Sprague-Dawley rats and chimeric rats, selectively expressing green fluorescent protein (GFP) in BMDCs. Their bilateral supraspinatus tendons were resected and sutured to the greater tuberosity of the humerus using the Masson-Allen technique, and G-CSF was subcutaneously injected for 5 days after surgery. Several GFP-positive cells were observed around the enthesis in the G-CSF-treated group compared with that in the Control group. Histological analysis revealed that the tendon-to-bone maturing scores and the Safranin O-stained cartilaginous areas were significantly higher in G-CSF-injected rats than in the control rats at weeks 4 and 8 after surgery. Consistently, the ultimate force to failure in the G-CSF-treated group significantly increased compared with the Control group at weeks 4 and 8 after surgery. These results suggest that BMDCs mobilized into the peripheral blood after G-CSF administration migrated to the rotator cuff repair area and effectively enhanced rotator cuff healing by promoting tenocyte and cartilage matrix production. In conclusion, the BMDC mobilization technique by G-CSF treatment via peripheral blood will provide a potential therapeutic approach for rotator cuff healing with clinically relevant applications. Impact statement As the retear rate following rotator cuff repair is high, new methods to aid its healing are required. Granulocyte colony-stimulating factor (G-CSF) has been used clinically and may represent a novel approach to treating rotator cuff tear. Herein, using a rat model, we elucidate the kinetics of bone marrow-derived mesenchymal stem cells at the repair site following G-CSF administration and describe the underlying mechanism by which G-CSF can help promote the repair of the rotator cuff.

Effect of Footprint Preparation on Tendon-to-Bone Healing: A Histologic and Biomechanical Study in a Rat Rotator Cuff Repair Model.

PURPOSE: To compare the histologic and biomechanical effects of 3 different footprint preparations for repair of tendon-to-bone insertions and to assess the behavior of bone marrow-derived cells in each method of insertion repair. METHODS: We randomized 81 male Sprague-Dawley rats and green fluorescent protein-bone marrow chimeric rats into 3 groups. In group A, we performed rotator cuff repair after separating the supraspinatus tendon from the greater tuberosity and removing the residual tendon tissue. In group B, we also drilled 3 holes into the footprint. The native fibrocartilage was preserved in groups A and B. In group C, we excavated the footprint until the cancellous bone was exposed. Histologic repair of the tendon-to-bone insertion, behavior of the bone marrow-derived cells, and ultimate force to failure were examined postoperatively. RESULTS: The areas of metachromasia in groups A, B, and C were 0.033 ± 0.019, 0.089 ± 0.022, and 0.002 ± 0.001 mm2/mm2, respectively, at 4 weeks and 0.029 ± 0.022, 0.090 ± 0.039, and 0.003 ± 0.001 mm2/mm2, respectively, at 8 weeks. At 4 and 8 weeks postoperatively, significantly higher cartilage matrix production was observed in group B than in group C (4 weeks, P = .002; 8 weeks, P < .001). In green fluorescent protein-bone marrow chimeric rats in group B, bone marrow-derived chondrogenic cells infiltrated the fibrocartilage layer. Ultimate force to failure was significantly higher in group B (19.7 ± 3.4 N) than in group C (16.7 ± 2.0 N) at 8 weeks (P = .031). CONCLUSIONS: Drilling into the footprint and preserving the fibrocartilage improved the quality of repair tissue and biomechanical strength at the tendon-to-bone insertion after rotator cuff repair in an animal model. CLINICAL RELEVANCE: Drilling into the footprint and preserving the fibrocartilage can enhance repair of tendon-to-bone insertions. This method may be clinically useful in rotator cuff repair.