Enhancement of tendon-bone healing after rotator cuff injuries using combined therapy with mesenchymal stem cells and platelet rich plasma

摘要

OBJECTIVE: The injuries of rotator cuff will cause the shoulder dysfunctions. Due to limited self-regeneration abilities of the tendon-bone part, rotator cuff injuries remain a clinical challenge. Previous studies have proposed many strategies for treating this disease. In this work, we aimed to combine different strategies to achieve better beneficial effects on tendon-bone repair. MATERIALS AND METHODS: We isolated mesenchymal stem cells (MSCs) and platelet-rich plasma (PRP) and tested the effects of PRP on the gene expression, cell death resistance, and osteogenic differentiation of MSCs. Then, we utilized multiple strategies to treat rotator cuff injuries. We evaluated the expression of genes that related to tissue repair, bone formation, and tendon regeneration. We also tested the biomechanical property of repair tissues. RESULTS: We found that the in-vitro co-culture with PRP endowed MSCs with enhanced production of growth factors, better osteogenic differentiation ability, and stronger ability to resist cell death. Next, we applied MSCs, PRP, and MSCs-PRP combined therapies in rat rotator cuff injury model to compare their therapeutic effects in vivo. Through biomechanical testing, we found that the combined therapy was most efficient to promote tissue regeneration and enhance the biomechanical property of the newly generated bone. CONCLUSIONS: The combined treatment induced strongest signals related to angiogenesis, bone formation, and tendon generation in-situ. We demonstrated that the combination of MSCs and PRP synergistically promotes tendon-bone healing and holds great promise for the treatment of rotator cuff injuries.