Mesenchymal stem cell expression of stromal cell-derived factor-1? augments bone formation in a model of local regenerative therapy.

ABSTRACT: Bone has the potential for spontaneous healing. However, this process often fails in patients with co-morbidities requiring clinical intervention. Numerous studies have revealed that bone marrow-derived mesenchymal stem/stromal cells (BMSCs) hold great potential for regenerative therapies. Common problems include poor cell engraftment, which can be addressed by irradiation prior to transplantation. Increasing evidence suggests that stromal cell-derived factor-1 (SDF-1) is involved in bone formation. However, osteogenic contributions of the beta splice variant of SDF-1 (SDF-1?), which is highly expressed in bone, remain unclear. Using the tetracycline (Tet)-regulatory system we have shown that SDF-1? enhances BMSC osteogenic differentiation in vitro. Here we test the hypothesis that SDF-1? augments bone formation in vivo in a model of local BMSC transplantation following irradiation. We found that SDF-1?, expressed at high levels in Tet-Off-SDF-1? BMSCs, augments the cell-mediated therapeutic effects resulting in enhanced bone formation, as evidenced by ex vivo ?CT and bone histomorphometry. The data demonstrate the specific contribution of SDF-1? to BMSC-mediated bone formation, and validate the feasibility of the Tet-Off technology to regulate SDF-1? expression in vivo. In conclusion, SDF-1? provides potent synergistic effects supporting BMSC-mediated bone formation and appears a suitable candidate for optimization of bone augmentation in translational protocols.

SUBMITTER: Herberg S 

PROVIDER: S-EPMC4706461 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature