The management of tendon tissue injury presents a significant clinical challenge due to the unique properties of tendons. Cell-based therapy provides a new alternative for regenerating functional tendons, such as in tendon rupture repair, but largely remains at the preclinical research stage. A cell source for graft preparation is essential for successful clinic application. In this study, a novel cell coculture system of bone marrow mesenchymal stem cells (BMSCs) and tendon-derived stem cells (TDSCs) was developed and investigated. BMSCs and TDSCs were cultured separately or in combination at ratios of 20:1, 10:1, 5:1, and 1:1 in vitro, and the cocultured cells showed an enhanced proliferation and collagenous protein production. The coculture system promoted tenogenic differentiation with enhanced tenogenic marker gene expression and collagen matrix production, particularly in the groups with a ratio of 1:1. Using a rat patellar tendon window injury model, we demonstrated that the cell sheets formed by cocultured cells promoted tendon healing significantly, compared to those with a single-cell source. Our study suggests that BMSCs and TDSCs cocultured at the 1:1 ratio may be an improved cell source/preparation for tendon tissue engineering.
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