Systemic Infusion of Mesenchymal Stem Cells Improves Cell-Based Bone Regeneration via Upregulation of Regulatory T Cells

Mesenchymal-stem-cell-based regenerative medicine is a promising approach for functional tissue reconstruction. A recent study showed that host immune cells regulated bone marrow mesenchymal stem cell (BMMSC)-mediated tissue regeneration. However, it is unknown whether systemic infusion of BMMSCs, which induces immune tolerance, affects cell-based tissue regeneration. In this study, we showed that BMMSCs possessed an immunomodulatory function in vitro. Moreover, systemic infusion of BMMSCs reduced IFN-gamma and TNF-alpha levels in the implantation sites via upregulation of regulatory T cells (Tregs), resulting in marked enhancement of cell-based bone regeneration, but with only limited contribution by BMMSC homing. Further, we showed that systemic BMMSC infusion significantly improved cell-based repair of critical-sized calvarial defects in a murine model. These results suggested a new approach to enhance cell-based bone regeneration.