Silencing of TGIF1 in bone mesenchymal stem cells applied to the post-operative rotator cuff improves both functional and histologic outcomes.

Stem cells have long been hypothesized to improve outcomes following rotator cuff repair. However, these cells must be signaled in order to do so. TGIF1 is a transcription factor that has been found to be down-regulated in cells involved in chondrogenesis. We therefore wished to examine whether stem cells expressing lower levels of TGIF1 could better improve outcomes following rotator cuff repair than stem cells expressing normal levels of TGIF1. Bone mesenchymal stem cells (BMSCs) were transduced with TGIF1 siRNA to suppress native TGIF1. Nontransduced BMSCs were also obtained for the control group. Following suprapinatus tendon repair, rats were either treated with transduced BMSCs or nontransduced BMSCs. Histologic and functional testing were performed on both groups. Rats treated with transduced TGIF1 siRNA BMSCs following suprapinatus repair expressed significantly higher levels of chondrogenic proteins at 4 weeks than rats treated with nontransduced BMSCs. Further, rats treated with BMSCs transduced with TGIF1 siRNA had both a significantly greater maximum load at failure and stiffness. Rats treated with transduced TGIF1 siRNA BMSCs following supraspinatus repair perform better both histologically and functionally at 4 weeks.