The Effect of Mesenchymal Stem Cell Sheets on Early Healing of the Achilles Tendon in Rats.

Bone marrow-derived mesenchymal stem cells (BMSCs) have potential to accelerate flexor tendon healing and allow for earlier rehabilitation. The ideal BMSC construct and delivery method to the repair site remains unknown. We investigated the efficacy of interposed scaffold-free BMSC sheets on early Achilles tendon healing in rats. BMSCs were isolated from the femora and tibias of male Sprague-Dawley rats aged 8-12 weeks and BMSC sheets were produced on temperature-responsive culture dishes. Ninety-five male Sprague-Dawley rats aged 8-12 weeks were utilized. A bilateral Achilles tendon repair model was created. One side was randomly selected, and the tendon was repaired with the interposed BMSC sheet (BMSC group). The other side was repaired without BMSCs (control group). The bilateral tendons were harvested at 5, 6, 7, 10, and 14 days postoperatively for biomechanical analysis, measurement of the gene expression level of tendon markers scleraxis and tenomodulin by real-time polymerase chain reaction, and histological evaluation. The BMSC group had significantly higher maximum load to failure and stiffness at 5 and 6 days compared with the control group. Moreover, the BMSC group showed significantly increased gene expression of scleraxis and/or tenomodulin at all timepoints. The cross sectional areas in the BMSC group were significantly larger at 5, 6, and 14 days. However, hematoxylin and eosin staining of the central part of the repair site revealed no significant differences at all timepoints. These results suggest that the increased biomechanical strength afforded by BMSC sheet implantation into tendon repair sites may allow for the earlier onset of rehabilitation and improved clinical outcomes in flexor tendon surgery. Impact Statement We investigated the efficacy of interposed bone marrow-derived mesenchymal stem cell (BMSC) sheets on early Achilles tendon healing in rats. The tendons repaired with BMSC sheets revealed significantly increased mechanical strength compared with the control repairs (without the BMSC sheet) at 5 and 6 days. These data reveal that BMSC sheet implantation into tendon repair sites may allow for earlier onset of rehabilitation and improved clinical outcomes in flexor tendon surgery.