title: Mesenchymal stem cell expression of stromal cell-derived factor-1β 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-1β), which is highly expressed in bone, remain unclear. Using the tetracycline (Tet)-regulatory system we have shown that SDF-1β enhances BMSC osteogenic differentiation in vitro. Here we test the hypothesis that SDF-1β augments bone formation in vivo in a model of local BMSC transplantation following irradiation. We found that SDF-1β, expressed at high levels in Tet-Off-SDF-1β BMSCs, augments the cell-mediated therapeutic effects resulting in enhanced bone formation, as evidenced by ex vivo μCT and bone histomorphometry. The data demonstrate the specific contribution of SDF-1β to BMSC-mediated bone formation, and validate the feasibility of the Tet-Off technology to regulate SDF-1β expression in vivo. In conclusion, SDF-1β provides potent synergistic effects supporting BMSC-mediated bone formation and appears a suitable candidate for optimization of bone augmentation in translational protocols.
authors.affiliation: Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio.
authors.forename: Samuel
authors.initials: S
authors.lastname: Herberg
authors.forename: Galina
authors.initials: G
authors.lastname: Kondrikova
authors.forename: Khaled A
authors.initials: KA
authors.lastname: Hussein
authors.forename: Maribeth H
authors.initials: MH
authors.lastname: Johnson
authors.forename: Mohammed E
authors.initials: ME
authors.lastname: Elsalanty
authors.forename: Xingming
authors.initials: X
authors.lastname: Shi
authors.forename: Mark W
authors.initials: MW
authors.lastname: Hamrick
authors.forename: Carlos M
authors.initials: CM
authors.lastname: Isales
authors.forename: William D
authors.initials: WD
authors.lastname: Hill
mesh_terms: D000818:Animals; D016025:Bone Transplantation; D054377:Chemokine CXCL12 / Q000378:metabolism*; D017102:Fracture Healing; D015316:Genetic Therapy; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D008810:Mice, Inbred C57BL; D010012:Osteogenesis; D013977:Tibia / Q000166:cytology / Q000637:transplantation
chemical_list: D054377:Chemokine CXCL12
keywords: BMSCs; SDF-1/CXCL12; bone formation; irradiation; stem cell transplantation